Renal Failure - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

RENAL FAILURE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Renal Failure: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84606-5 1. Renal Failure-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on renal failure. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 9 CHAPTER 1. STUDIES ON RENAL FAILURE ...................................................................................... 11 Overview...................................................................................................................................... 11 The Combined Health Information Database............................................................................... 11 Federally Funded Research on Renal Failure............................................................................... 25 E-Journals: PubMed Central ....................................................................................................... 82 The National Library of Medicine: PubMed ................................................................................ 85 CHAPTER 2. NUTRITION AND RENAL FAILURE ............................................................................ 133 Overview.................................................................................................................................... 133 Finding Nutrition Studies on Renal Failure.............................................................................. 133 Federal Resources on Nutrition ................................................................................................. 137 Additional Web Resources ......................................................................................................... 138 CHAPTER 3. DISSERTATIONS ON RENAL FAILURE ........................................................................ 141 Overview.................................................................................................................................... 141 Dissertations on Renal Failure .................................................................................................. 141 Keeping Current ........................................................................................................................ 142 CHAPTER 4. CLINICAL TRIALS AND RENAL FAILURE .................................................................. 143 Overview.................................................................................................................................... 143 Recent Trials on Renal Failure .................................................................................................. 143 Keeping Current on Clinical Trials ........................................................................................... 156 CHAPTER 5. PATENTS ON RENAL FAILURE................................................................................... 159 Overview.................................................................................................................................... 159 Patents on Renal Failure............................................................................................................ 159 Patent Applications on Renal Failure ........................................................................................ 179 Keeping Current ........................................................................................................................ 213 CHAPTER 6. BOOKS ON RENAL FAILURE ...................................................................................... 215 Overview.................................................................................................................................... 215 Book Summaries: Federal Agencies............................................................................................ 215 Book Summaries: Online Booksellers......................................................................................... 220 Chapters on Renal Failure.......................................................................................................... 227 CHAPTER 7. MULTIMEDIA ON RENAL FAILURE............................................................................ 245 Overview.................................................................................................................................... 245 Video Recordings ....................................................................................................................... 245 Audio Recordings....................................................................................................................... 246 CHAPTER 8. PERIODICALS AND NEWS ON RENAL FAILURE ........................................................ 249 Overview.................................................................................................................................... 249 News Services and Press Releases.............................................................................................. 249 Newsletters on Renal Failure..................................................................................................... 252 Newsletter Articles .................................................................................................................... 253 Academic Periodicals covering Renal Failure ............................................................................ 256 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 259 Overview.................................................................................................................................... 259 U.S. Pharmacopeia..................................................................................................................... 259 Commercial Databases ............................................................................................................... 263 Researching Orphan Drugs ....................................................................................................... 264 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 269 Overview.................................................................................................................................... 269 NIH Guidelines.......................................................................................................................... 269 NIH Databases........................................................................................................................... 271 Other Commercial Databases..................................................................................................... 273 The Genome Project and Renal Failure...................................................................................... 273

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APPENDIX B. PATIENT RESOURCES ............................................................................................... 277 Overview.................................................................................................................................... 277 Patient Guideline Sources.......................................................................................................... 277 Finding Associations.................................................................................................................. 306 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 309 Overview.................................................................................................................................... 309 Preparation................................................................................................................................. 309 Finding a Local Medical Library................................................................................................ 309 Medical Libraries in the U.S. and Canada ................................................................................. 309 ONLINE GLOSSARIES................................................................................................................ 315 Online Dictionary Directories ................................................................................................... 315 RENAL FAILURE DICTIONARY............................................................................................... 317 INDEX .............................................................................................................................................. 431

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with renal failure is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about renal failure, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to renal failure, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on renal failure. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to renal failure, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on renal failure. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON RENAL FAILURE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on renal failure.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and renal failure, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “renal failure” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Prevention and Treatment of Acute Renal Failure in Sepsis Source: JASN. Journal of the American Society of Nephrology. 14(3): 792-805 March 2003. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Website: www.jasn.org/. Summary: Acute renal failure (ARF) is a common complication of sepsis and has a poor prognosis. Mortality (death) was reported higher in patients with septic ARF (74.5 percent) than in those whose renal (kidney) failure did not result from sepsis (45.2 percent). This article discusses the use of drug therapy to interfere with each of the dysfunctional pathways to improve the course of septic ARF. These include inhibition of inflammatory mediators, improvement of renal hemodynamics (blood flow) by

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amplifying vasodilator mechanisms and blocking vasoconstrictor mechanisms, interruption of leukocyte infiltration, inhibition of the coagulation cascade, and administration of growth factors to accelerate renal recovery. The author also highlights the available supportive measures, including dialysis, that can be used for septic patients with ARF. The author notes that, unfortunately, treatment of ARF in sepsis is still only supportive; there have been no conclusive drug therapies available to treat the condition. 1 figure. 1 table. 136 references. •

Impact of Burn Size and Initial Serum Albumin Level on Acute Renal Failure Occurring in Major Burn Source: American Journal of Nephrology. 23: 55-60. January-February 2003. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479. Website: www.karger.com. Summary: Acute renal (kidney) failure (ARF) is not a rare occurrence in severe burns and is an important complication leading to an increase in mortality (death). The severity of the burn is largely determined by the burn size, and severe burns are likely to cause enough loss of extracellular fluid and albumin from plasma volume to produce shock and hypoalbuminemia (low levels of the protein albumin in the blood). This article reports on a study in which the authors hypothesized that initial serum albumin level may be useful as an indicator of prognosis and severity of injury in burned patients. The authors retrospectively analyzed the clinical characteristics of 147 adult patients with second-and third-degree burns covering 30 percent or more of their body surface area. Of the 147 patients, 27 (19 percent) experienced ARF, defined as a serum creatinine greater than 2 milligrams per deciliter, during the admission. The patients with ARF had larger burn size and lower serum albumin concentration at admission, compared with those without ARF. All patients with ARF expired, whereas 29.4 percent (35 of 119 patients) of the patients without ARF died. The burn size greater than 65 percent was associated with a risk of ARF that was 9.9 times and with a risk of death that was 14.2 times as high as that for burn size less than 65 percent. The authors conclude that when major burns are complicated by ARF, the mortality rate increases significantly. Burn size is an independent predictor of ARF occurring in major burns. Initially depressed serum albumin level is associated with an increase in mortality in the major burn patients. 3 figures. 4 tables. 21 references.

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Slowing the Progression of Chronic Renal Failure: Economic Benefits and Patients' Perspectives Source: American Journal of Kidney Diseases. 39(4): 721-729. April 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Because of the predicted increase in end stage renal disease (ESRD) incidence, prevalence, and cost, a cohesive national effort is needed to develop strategies to slow the progression of chronic renal (kidney) failure (CRF). The question arises of how much reduction in the progression of CRF would lead to a meaningful decrease in the prevalence and cost of ESRD. This article reports on the development of a mathematical model to assess the economic impact of decreasing the progression of CRF by 10 percent, 20 percent, and 30 percent. United States Renal Data System (USRDS) projections were used to model the rate of increase in ESRD incidence and prevalence. Glomerular filtration rate (GFR, a measure of kidney function) at the initiation of ESRD therapy and cost per patient year were based on USRDS data. The authors also

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determined how much slowing of the progression of CRF is important from patients' perspectives by means of a written questionnaire (which inquired about willingness to go on a restricted diet, take six extra medications per day, and make six extra office visits per year). The authors note that their data suggest that the cumulative economic impact of slowing the progression of CRF, even by as little as 10 percent, would be staggering. The authors call for the development and implementation of intensive renoprotective (protecting the kidney) efforts beginning at the early stages of chronic renal disease and continued throughout its course. 2 figures. 5 tables. 48 references. •

Precision of Estimating Protein Intake of Patients with Chronic Renal Failure Source: Kidney International. 62(5): 1750-1756. November 2002. Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: Biochemical methods for estimating protein intake are based on the concept that nitrogen-containing products of protein in diet, plus the products arising from endogenous protein, are excreted as either urea or non-urea nitrogen (NUN). The urea nitrogen appearance (UNA) rate is measured as the amount of urea excreted in urine plus the net amount accumulated in body water. This article reports on a study in which the authors examined nitrogen balance and its components measured in 33 patients with chronic renal (kidney) failure (CRF) who were eating diets varying from 4.1 to 10.1 grams of nitrogen per day. The authors evaluated relationships between dietary nitrogen, NUN, fecal nitrogen, body weight, and the predictability of the two methods of measurement (a standard measure of nitrogen intake versus a recently-proposed measure named for Maroni). The authors conclude that fecal nitrogen is not correlated with nitrogen intake, NUN is not constant but varies with weight, and the traditional method of estimating nitrogen intake in stable chronic renal insufficiency (CRI) patients from UNA and weight as proposed by Maroni et al is valid. 4 figures. 2 tables. 30 references.

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Renal Osteodystrophy in Chronic Renal Failure Source: Seminars in Nephrology. 22(6): 488-493. November 2002. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Bone disease develops relatively early in the development of chronic renal (kidney) failure (CRF). Renal osteodystrophy is the nonspecific term used to describe the many bone and mineral complications associated with renal disease. This article explores renal osteodystrophy in CRF. The authors note that much of what is known about the evaluation and management of renal osteodystrophy in CRF is based on knowledge obtained in the dialysis population. The classic bone lesion found in the dialysis population is osteitis fibrosa, the high turnover lesion of secondary hyperparathyroidism. Clearly, hypocalcemia (low levels of calcium in the blood), hyperphosphatemia (high levels of phosphate in the blood), and calcitriol deficiency play major roles in the development and maintenance of the high turnover disease. Interestingly, in both the dialysis and nondialysis population, the incidence of adynamic bone disease, a low turnover lesion, is increasing. The authors postulate that the aggressive use of calcium-containing phosphate binders and the use of calcitriol and other vitamin D analogs to treat secondary hyperparathyroidism may contribute to this shift in bone lesions. Treatment in the nondialysis kidney disease patient remains aggressive correction of hypocalcemia and hyperphosphatemia. The use of calcitriol and

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other agents to maintain serum calcium and to suppress elevated parathyroid hormone remains well supported. However, the increase in extraskeletal calcifications and incidence of adynamic bone disease in these patients raises concern about current management techniques. 1 figure. 2 tables. 35 references. •

Renal Failure and Deafness: Branchio-Oto-Renal Syndrome Source: American Journal of Kidney Diseases. 32(2): 334-337. August 1998. Contact: Available from W.B. Saunders Company. P.O. Box 628239, Orlando, FL 328628239. (800) 654-2452. Fax (800) 225-6030. E-mail: [email protected]. Website: www.ajkd.org. Summary: Branchio oto renal (BOR) syndrome is a rare autosomal dominant condition that may present with hearing loss, branchial cysts, and renal failure. The characteristic phenotypic expression of the full syndrome may be partial or complete, and a whole range of renal (kidney) abnormalities may be present. The similarity of BOR to Alport's syndrome may lead to misdiagnosis. This article presents a case report of adult onset renal failure in a 44 year old white man with deafness, previously believed to have Alport's syndrome. The patient's hearing loss was believed to be congenital, and he was prescribed hearing aids. By the age of 19 years, deafness had worsened significantly, and a diagnosis of bilateral moderately severe mixed hearing loss was made. The authors review the relevant literature. The authors note that it is not clear why there is an association between renal malformation and abnormalities of the ear. 2 figures. 18 references.

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Varicella Vaccination in Children with Chronic Renal Failure: A Report of the Southwest Pediatric Nephrology Study Group Source: Pediatric Nephrology 18(1): 33-38. January 2003. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: Children with kidney disease are at risk for serious varicella related complications. This article reports on a study undertaken to evaluate the safety and immunogenicity of a two-dose regimen of varicella (the virus that causes chickenpox) vaccine in children (aged 1 to 19 years, n = 96) with chronic renal (kidney) insufficiency and on dialysis. Of the 96 patients, 50 (mean age 4.2 years) had no detectable varicella zoster virus (VZV) antibody; 98 percent sero-converted after the two-dose vaccine regimen. At 1, 2, and 3 years' follow up, all patients studied maintained VZV antibody, including 16 who received a transplant. No significant vaccine-associated adverse events were seen. One subject developed mild varicella 16 months post transplant. In multivariate regression analysis, patients vaccinated after 6 years of age had VZV antibody levels 73 percent lower than patients vaccinated before 6 years of age. The authors conclude that a two-dose varicella vaccination regimen was generally well tolerated and highly immunogenic in children with chronic kidney disease. 1 figure. 2 tables. 25 references.

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Hepatitis C and Renal Failure Source: American Journal of Medicine. 107(6B): 90S-94S. December 27, 1999. Contact: Available from Exerpta Medica, Inc. American Journal of Medicine, P.O. Box 7247-7197, Philadelphia, PA 19170-7197. (800) 606-0023 or (609) 786-0841. Fax (609) 7867032.

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Summary: Chronic hepatitis C virus (HCV) infection is common among patients with chronic renal (kidney) failure (CRF). This article reviews the interplay between HCV and kidney failure. The chronic viral infection can result in significant morbidity (illness) and mortality (death). Liver failure from chronic hepatitis C is one of the leading causes of death among long term survivors of kidney transplantation. Between 10 and 20 percent of patients on hemodialysis are chronically infected with HCV. HCV infection also can be a cause of glomerulonephritis (and infection of the kidneys) and nephrotic syndrome (edema, or fluid accumulation, protein in the urine or proteinuria, and susceptibility to infections). The author stresses that primary care physicians need to recognize these conditions in order to optimize the management of patients with CRF. 45 references. •

Influence of Dialysis Membranes on Outcomes in Acute Renal Failure: a MetaAnalysis Source: Kidney International. 62(5): 1819-1823. November 2002. Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: Considerable controversy exists as to whether synthetic (more biocompatible) dialysis membranes improve outcome in patients with acute renal (kidney) failure (ARF) compared to cellulose-based membranes. This article reports on a meta-analysis performed on all previously published prospective trials comparing the use of synthetic membranes with cellulose-based membranes for hemodialysis (HD) in patients with ARF. Of the 10 prospective trials identified, 8 trials (867 patients) provided survival data and six trials (641 patients) provided data on recovery of renal function. The authors conclude that synthetic membranes appear to confer a significant survival advantage over cellulose-based membranes. The authors could not demonstrate a similar benefit with use of synthetic membranes over cellulose-based membranes for recovery of renal function, but sample size was limited. The authors note that the survival disadvantage for cellulose-based membranes may be limited to unsubstituted cellulose (cuprophane) membranes. 2 figures. 1 table. 18 references.

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Some Medical Aspects of Nutritional Therapy in Elderly Chronic Renal Failure Patients Source: Dialysis and Transplantation. 31(9): 607-608, 610-614. September 2002. Contact: Available from Dialysis and Transplantation, Attn.: Subscriptions. P.O. Box 10535, Riverton, NJ 08076. (800) 624-4196 or (609) 786-0871. Summary: Elderly chronic renal (kidney) failure (CRF) patients present special problems to the renal team. This article focuses on some medical aspects of nutritional therapy in elderly CRF patients. The authors note that signs due to aging often superimpose on symptoms related to CRF. There are some specific age-associated problems in geriatric patients, such as diminished taste and smell perception, loss of teeth, constipation, poor physical condition, and psychosocial problems including economic limitations, social isolation, and depression. All of these conditions can have a negative impact on the nutritional status in elderly CRF patients. The authors advise a moderate protein restriction and an increased calorie intake in elderly renal patients who are in the Predialysis stage. Metabolic acidosis should be treated to prevent further catabolism, and more intensive nutritional monitoring is advocated to avoid occult (hidden) malnutrition. The authors also discuss the nutritional recommendations for elderly patients on hemodialysis and comment on a new therapeutic trend for the treatment of

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malnutrition in CRF patients, i.e., the use of recombinant forms of human growth hormone and insulin-like growth factor 1. 3 figures. 1 table. 25 references. •

Inflammation and Outcome in End-Stage Renal Failure: Does Female Gender Constitute a Survival Advantage? Source: Kidney International. 62(5): 1791-1798. November 2002. Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: Elevated C-reactive protein (CRP) is a strong predictor of cardiovascular events and all-cause mortality (death) in patients with end stage renal disease (ESRD). However, although sex hormones may influence serum levels of inflammatory proteins, gender has not been taken into consideration in previous studies of inflammation and outcome in ESRD patients. This article reports on a study of 663 ESRD patients (374 males) aged 59 years (plus or minus 1 year) from three European renal (kidney) centers (Sweden, Germany, Italy). The relation between outcome and serum levels of the soluble intercellular adhesion molecule (sICAM-1) was evaluated in 312 of the patients. The results show that elevated CRP is a strong predictor of outcome. No difference in allcause mortality was observed between noninflamed males and females. However, inflamed males had a significantly higher mortality rate than inflamed females. The authors conclude that sex hormones may have important cardioprotective effects that limit the effect of inflammation on vascular injury in female ESRD patients. 3 figures. 2 tables. 28 references.

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Hemofiltration and Peritoneal Dialysis in Infection-Associated Acute Renal Failure in Vietnam Source: New England Journal of Medicine. 347(12): 895-902. September 19, 2002. Summary: In some parts of the world, peritoneal dialysis (PD) is widely used for renal replacement therapy (RRT) in acute renal (kidney) failure (ARF). In resource-rich countries, it has been supplanted in recent years by hemodialysis (HD) and, most recently, by hemofiltration and associated techniques. This article reports on an open, randomized comparison study of pumped venovenous hemofiltration and peritoneal dialysis in patients with infection-associated ARF in an infectious disease referral hospital in Vietnam. The study included 70 adult patients with severe falciparum malaria (n = 48) or sepsis (n = 22); 34 were assigned to hemofiltration and 36 to PD. The mortality rate was 47 percent (17 patients) in the group assigned to PD, compared to 15 percent (5 patients) in the group assigned to hemofiltration. The rates of resolution of acidosis and of decline in the serum creatinine concentration in the group assigned to hemofiltration were more than twice those in the group assigned to peritoneal dialysis and RRT was required for a significantly shorter period. The cost of hemofiltration per survivor was less than half that of PD, and the cost per life saved was less than one third. The authors conclude that hemofiltration is superior to peritoneal dialysis in the treatment of infection-associated acute renal failure. 2 figures. 2 tables. 11 references.

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Slowing the Course of Renal Failure in Patients with Diabetes Source: Physician Assistant. 16(10): 79-85. October 1992. Summary: In this article, the authors discuss the incidence and costs involved in diabetes-associated renal disease; the typical course of renal disease in patients with diabetes; the mechanisms of said renal disease; nonpharmacologic intervention; and

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pharmacologic intervention, including the use of diuretics, beta blockers, vasodilators, ACE inhibitors and calcium antagonists, and combination therapy. The authors conclude that aggressive early blood pressure control has been shown to postpone the development of end-stage renal disease significantly and hypothesize that the ACE inhibitors and certain classes of calcium antagonists have the potential to modify the course of diabetic nephropathy even more than traditional antihypertensive therapy. 43 references. •

Impact of Simultaneous Pancreas and Kidney Transplantation on Progression of Coronary Atherosclerosis in Patients with End-Stage Renal Failure due to Type 1 Diabetes Source: Diabetes Care. 25(5): 906-911. May 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Mortality (death) in type 1 diabetes patients with end stage renal failure is high and is dominated by coronary (heart) atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in these patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. This article reports on a study that compared progression of coronary atherosclerosis in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK. Mean follow up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft. Regression of atherosclerosis occurred in 38 percent of patients with a functioning pancreas graft compared with 0 percent of patients in whom the pancreas graft was lost. The authors conclude that this observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetes patients with end stage renal failure after SPK compared with KTA. In light of these findings, the authors recommend that SPK be carefully considered for all diabetes transplant candidates. 3 figures. 1 table. 40 references.

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Peritoneal Dialysis in Acute Renal Failure: Why the Bad Outcome? (editorial) Source: New England Journal of Medicine. 347(12): 933-935. September 19, 2002. Summary: Mortality rates among patients with acute renal (kidney) failure (ARF) can be quite high, but because this diagnosis encompasses a broad mix of patients, optimal treatment strategies are sometimes not clear. This editorial comments on a research study (published in the same journal issue) that provides evidence of the superiority of venovenous hemofiltration over peritoneal dialysis in patients with ARF. The editorial author considers whether some adverse factor associated with peritoneal dialysis as it was used in this study may also have affected survival. The editorial discusses the equipment and supplies used and the problem of high glucose levels in peritoneal dialysis fluid. The author concludes that, in addition to comparing the ability of peritoneal dialysis, continuous renal replacement therapy, and hemodialysis to remove solute, salt, and water in patients with ARF, it must also be determined whether there are technique-specific factors that affect outcome. 8 references.

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Nutrition in Children with Preterminal Chronic Renal Failure: Myth or Important Therapeutic Aid? Source: Pediatric Nephrology. 17(2): 111-120. February 2002. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: Nutrition has been believed to be an important therapeutic instrument in children with chronic renal (kidney) failure for improving growth and for slowing down the deterioration of renal function. The therapeutic strategies for both targets may be conflicting, at least in part, since a high caloric intake is needed for optimal growth, whereas a low protein diet, which was believed to protect renal function, places patients at risk of low calorie intake. This review article considers the role of nutrition in children with preterminal chronic renal failure (CRF). Dietary manipulations for optimal growth are mainly effective in infants with CRF. However, growth remains suboptimal even with an energy intake above 80 percent of RDA. Although a low protein diet is able to slow down the rate of deterioration in renal function in rodent studies, the results of prospective clinical studies were disappointing, at least for an observation period up to three years. The conclusions from dracon meta-analyses of these clinical studies in adults are contradictory. The progression rate was not significantly influenced by protein restriction, whereas renal replacement therapy could be postponed. However, the latter seems to be the effect of weakening uremic symptoms during the phase of end stage renal failure. The authors conclude that, according to present knowledge, it is not justified to prescribe special diets to children early in the course of CRF, but the composition of their nutrition should follow the general concept of an optimal mixed diet. 2 figures. 2 tables. 143 references.

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Dialysis, Kidney Transplantation, or Pancreas Transplantation for Patients with Diabetes Mellitus and Renal Failure: A Decision Analysis of Treatment Options Source: Journal of the American Society of Nephrology. 14(2): 500-515. February 2003. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Website: www.jasn.org/. Summary: Patients with type 1 diabetes mellitus and end stage renal (kidney) disease (ESRD) may remain on dialysis or undergo cadaveric kidney transplantation, living kidney transplantation, sequential pancreas-after-living kidney transplantation, or simultaneous pancreas-kidney transplantation. This article reports on a study undertaken to determine the optimal treatment strategy for type 1 diabetes patients with kidney failure. The outcome measures were life expectancy in life-years (LY) and quality-adjusted life expectancy in quality-adjusted life-years (QALY). Living kidney transplantation was associated with 18.30 LY and 10.29 QALY; pancreas after kidney transplantation, 17.21 LY and 10.00 QALY; simultaneous pancreas-kidney transplantation, 15.74 LY and 9.09 QALY; cadaveric kidney transplantation, 11.44 LY and 6.53 QALY; dialysis, 7.82 LY and 4.52 QALY. The results were sensitive to the value of several key variables. Simultaneous pancreas-kidney transplantation had the greatest life expectancy and quality-adjusted life expectancy when living kidney transplantation was excluded from the analysis. The data indicate that living kidney transplantation is associated with the greatest life expectancy and quality-adjusted life expectancy for type 1 diabetes patients with renal failure. Treatment strategies involving pancreas transplantation should be considered for patients with frequent metabolic complications of diabetes. For patients without a living donor, simultaneous pancreas-kidney

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transplantation is associated with the greatest life expectancy. 5 figures. 4 tables. 162 references. •

Effects of Secondary Hyperparathyroidism Treatments on Blood Pressure and Lipid Levels in Chronic Renal Failure Patients Source: Transplantation Proceedings. 34(6): 2041-2043. September 2002. Contact: Available from Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010. (212) 633-3730. Website: www.elsevier.com. Summary: Secondary hyperparathyroidism, a frequent complication in chronic renal (kidney) failure (CRF) patients, is generally managed by controlling hyperphosphatemia, normalizing serum calcium levels, and administering oral or intravenous active vitamin D metabolites. Parathyroidectomy (PTX) is another treatment option when medical therapy fails to control the disease. This article reports on a study undertaken to investigate the effects of medical and surgical therapy on blood pressure and lipid levels in CRF patients. In this study, both medical and surgical therapies resulted in a significant decline in systolic and diastolic blood pressure. The authors conclude that treatment of secondary hyperparathyroidism has beneficial effects not only on renal osteodystrophy (bone disease associated with kidney disease), but also on blood pressure and triglyceride levels. They emphasize the need for surgical treatment of patients who are unresponsive to medical therapy. 4 figures. 13 references.

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Gastrointestinal Complications of Renal Failure Source: Gastroenterology Clinics of North America. 27(4): 875-892. December 1998. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Seventy-five percent of patients with end-stage renal disease (ESRD) have gastrointestinal complaints. Although some of these complaints may be specifically related to the techniques and procedures of the dialysis method itself, the physiologic state of chronic uremia is likely to contribute to the development of the majority of symptoms. Uremia is the presence of excessive amounts of urea and other nitrogen waste products in the blood. This article begins with a brief review of the systemic effects of uremic toxins followed by a review of the effects of the uremic state on the esophagus, stomach, duodenum, and pancreas. The effects of ESRD on the gastrointestinal (GI) tract can be divided into complications directly attributable to dialysis and complications that are more systemically related. The majority of complications are likely to be related to the latter. Dialysis related GI complications include peritonitis and sclerosing peritonitis. Esophageal abnormalities associated with the uremic state include esophagitis, motility disorders, and hiatal hernia. Stomach involvement in ESRD can include gastritis and duodenitis (infections), abnormal gastric emptying, peptic ulcer disease, and vascular ectasias (blood vessel distension). Other problems can include amyloidosis, abnormal pancreatic morphology, and pancreatitis. The author concludes that unless the supply of donor kidneys increases dramatically, these complications of ESRD will continue to be an important clinical issue for gastroenterologists, given the large percentage of patients with symptoms. 4 tables. 99 references.

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Acute Renal Failure Mortality in Hospitalized African Americans: Age and Gender Considerations Source: Journal of the National Medical Association. 94(3): 127-134. March 2002. Summary: The aging kidney is at risk for both toxic and hemodynamic induced acute damage, resulting in a high incidence of acute renal (kidney) failure (ARF) in elderly patients. This article reports on a 3 year computer assisted retrospective review in which the effect of age and or gender in ARF mortality in African Americans (AA) was studied. In an inner city medical center, 100 patients classified as ARF at discharge or death were included in the study. Patients were classified into 3 age categories: younger than 40 years, 40 to 64 years, and older than 64 years. The incidence of ARF was 35 percent, 28 percent, and 37 percent, respectively. Patients greater than 64 years of age were less likely to be put on dialysis. Both pre and post renal causes of ARF were more common in patients greater than 64 years of age than in younger patients. Hospital length of stay increased progressively with age. Mortality (rate of death) was lower in patients older than 64 years of age than in younger patients. The incidence of ARF was higher in male than female patients and the incidence of sepsis (generalized infection) was higher in female than male patients. Dialysis need was greater in male patients, but mortality was higher in female than male patients. Analyses showed that in the presence of sepsis, oliguria (decreased ability to form urine) and mechanical ventilatory support, the relative risk of mortality associated with advanced age was 16.5, the relative risk of mortality associated with female gender was 0.2. In summary, hospitalized elderly AA patients have a high incidence of ARF, and patients less than 40 years of age are equally at risk. Although mortality was higher in female patients, gender and advanced age did not independently contribute to high mortality. Neither age nor gender considerations should replace sound clinical judgement in the management of and decision making in elderly African American patients with ARF. 5 figures. 3 tables. 25 references.

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Microvascular Endothelial Injury and Dysfunction During Ischemic Acute Renal Failure Source: Kidney International. 62(5): 1539-1549. November 2002. Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: The pathophysiology of ischemic (lack of blood flow) acute renal failure (ARF) appears to involve a complex interplay between renal (kidney) hemodynamics, tubular injury, and inflammatory processes. A growing body of evidence supports the contribution of altered renal vascular function (the blood flow) in potentially starting and subsequently extending the initial tubular injury. In this article, the authors propose that the 'extension phase' of ischemic ARF involves changes in renal perfusion, continued hypoxia (inadequate levels of oxygen), and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial (the lining of the blood vessels) cell injury and dysfunction play a vital part in this extension phase. Vascular congestion, edema (fluid accumulation) formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction have been difficult. The authors explore how new investigative approaches can further the understanding of the pathophysiology of ischemic ARF. This, in turn, should provide new diagnostic and therapeutic approaches to ischemic ARF. 4 figures. 132 references.

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Early Initiation of Dialysis Fails to Prolong Survival in Patients With End-Stage Renal Failure Source: JASN. Journal of the American Society of Nephrology. 13 (8): 2125-2132. August 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: There is a trend to start dialysis earlier in patients with chronic renal (kidney) failure (CRF). Studies that suggest improved survival from earlier initiation are flawed in that they have measured survival from start of dialysis rather than from a time point before dialysis, when patients have the same renal function. This flaw is termed leadtime bias. This article reports on a study that used the electronic patient record at the renal unit of Glasgow Royal Infirmary to identify all patients who had received dialysis for CRF and who had sufficient data to calculate the time point that they reached a certain level of creatinine clearance (a measure of kidney function). This date was used to time survival. Results showed no significant benefit in patient survival from earlier initiation of dialysis. Patients who started dialysis with a lower estimated creatinine clearance tended to survive longer. This relationship retained significance when gender, age, weight, presence of diabetes, mode of first dialysis, initial dialysis access, hemoglobin, serum albumin, blood leukocyte count, Wright Khan index, and estimated creatinine clearance at the start of dialysis were taken into account. The authors conclude that their study fails to support a policy of earlier initiation of dialysis for patients with end stage renal disease (ESRD). 3 figures. 4 tables. 30 references.

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Eight-Year-Old Boy with Recurrent Macroscopic Hematuria, Weight Loss, and Kidney Failure Source: The Journal of Pediatrics. 142(3): 342-345. March 2003. Contact: Mosby, Inc. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: This article describes a case of an 8 year old boy who was examined by the authors in the emergency department; the boy had a third episode of macroscopic hematuria (visible blood in the urine), which had lasted for 6 days. This symptom was accompanied by a dull, bilateral back and paraumbilical abdominal pain of moderate intensity. The color of the urine was dark brown (tea-colored). The authors describe the case in detail and then consider the differential diagnosis. When the boy's clinical course deteriorated and a rapidly progressive renal insufficiency ensued, a definite histologic diagnosis was sought with kidney biopsy. The histopathologic diagnosis was a primary malignant non-Hodgkin lymphoma with a precursor T-cell phenotype. 3 figures. 19 references.

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Hypokalemic Salt-Losing Tubulopathy with Chronic Renal Failure and Sensorineural Deafness Source: Pediatrics. 108(1): [9 p.]. July 2001. Contact: Available from American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (888) 227-1773. Fax (847) 434-8000. E-mail: [email protected]. Website: www.pediatrics.org. Full text of this article is available at www.pediatrics.org/cgi/content/full/108/1/e5.

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Summary: This article describes a rare inherited hypokalemic (low levels of potassium) salt losing tubulopathy (kidney disease) with linkage to chromosome 1p31. The authors conducted a retrospective analysis of the clinical data for 7 patients in whom cosegregation of the disease with chromosome 1p31 had been demonstrated. In addition, in 1 kindred, prenatal diagnosis in the second child was established, allowing a prospective clinical evaluation. Clinical presentation (symptoms) of the patients was similar and included premature birth attributable to polyhydramnios, severe renal (kidney) salt loss, normotensive hyperreninemia, hypokalemic alkalosis, and excessive hyperprostaglandin E urea, which suggested the diagnosis of hyperprostaglandin E syndrome and antenatal Bartter syndrome. However, the response to indomethacin was only poor, accounting for a more severe variant of the disease. The patients invariably developed chronic renal failure. The majority had extreme growth retardation, and motor development was markedly delayed. In addition, all patients turned out to be deaf. The authors conclude that this hypokalemic salt losing tubulopathy with chronic kidney failure and sensorineural deafness represents not only genetically but also clinically a disease entity distinct from hyperprostaglandin E syndrome and antenatal Bartter syndrome. A pleiotropic (causing multiple, seemingly unrelated symptoms) effect of a single gene defect is most likely causative for syndromic hearing loss. 6 figures. 1 table. 41 references. •

Chronic Renal Failure: Slowing the Onset, Changing the Course Source: Patient Care. 33(19): 76, 78, 83-88. November 30, 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article provides health professionals with guidelines for detecting and managing chronic renal disease. Patients who have diabetes mellitus or hypertension are at greatest risk for developing end stage renal disease (ESRD). Patients who have diabetes and microalbuminuria are at substantially increased risk for developing overt renal disease and for death from cardiovascular disease. The early markers of kidney disease, urine protein and serum creatinine levels, can provide valuable information about kidney function. Although proteinuria/albuminuria indicates the onset of diabetic nephropathy, it is also an important early independent marker for kidney disease in patients who have essential hypertension and perhaps other nondiabetic renal diseases. The magnitude of protein in the urine appears to predict rate of progression to ESRD. Patients who have persistent protein excretion of 3 grams per day or more seem to progress to ESRD the fastest. The American Diabetes Association suggests that screening for microalbuminuria begin at diagnosis in patients who have type 2 diabetes, at puberty for children who have type 1 diabetes, and 5 years after onset of type 1 diabetes in older patients. Although serum creatinine is one of the best measures of kidney function, minor elevations are often considered insignificant, and a significantly elevated level is frequently overlooked as an important disease marker. Women with creatinine levels greater than 1.2 milligrams (mg) per deciliter (dL) and men with levels greater than 1.4 mg/dL should undergo further evaluation for kidney dysfunction. Other tests for kidney disease include kidney biopsy. Although whether to order a kidney biopsy for diabetic patients is controversial, a reasonable approach is to obtain a biopsy if there is any doubt or clinical findings are not typical for diabetic nephropathy. Strategies for slowing the progression of renal disease in people who have diabetic nephropathy include controlling blood pressure using angiotensin converting enzyme inhibitors. Sodium restriction may be beneficial for all patients who have renal insufficiency and proteinuria. Complications of ESRD include anemia, metabolic

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acidosis, and osteodystrophy. Early assessment by a nephrology specialist is important. 3 figures. 2 tables. 9 references. •

Enalapril and Losartan Reduce Sympathetic Hyperactivity in Patients with Chronic Renal Failure Source: JASN. Journal of the American Society of Nephrology. 14(2): 425-430. February 2003. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: This article reports on a study undertaken to compare the effects on blood pressure (BP) and sympathetic activity of chronic treatment with an ACE inhibitor (enalapril) and an AngII receptor blocker (losartan) in hypertensive patients (n = 10) with chronic renal (kidney) failure (CRF). Normovolemia was controlled with diuretics and confirmed with extracellular fluid volume measurements throughout the study. Both enalapril and losartan reduced muscle sympathetic nerve activity (MSNA) and average 24 hour BP. Plasma renin activity (PRA) was not different during the treatments; baroreceptor sensitivity was not affected by the treatment. The authors conclude that in hypertensive CRF patients, enalapril and losartan equally reduced BP and MSNA. Differences in modes of action of the two drugs did not result in differences in effects on MSNA, supporting the view that AngII-mediated mechanisms contribute importantly in the pathogenesis of sympathetic hyperactivity in these patients. 3 figures. 1 table. 30 references.

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Effect of Restricting Dietary Protein on the Progression of Renal Failure in Patients with Insulin-Dependent Diabetes Mellitus Source: New England Journal of Medicine. 324(2): 78-84. January 10, 1991. Summary: This article reports on research that studied the effect of reduced intake of protein and phosphorus on the progression of renal disease in 35 patients with insulindependent diabetes mellitus (IDDM) and clinically evident nephropathy. The lowprotein, low-phosphorus diet contained 0.6 g of protein per kilogram of ideal body weight per day, 500 to 1000 mg of phosphorus, and 2000 mg of sodium. The control diet consisted of the patient's prestudy diet with the stipulation that it contain 2000 mg of sodium and at least 1 g of protein per kilogram per day and 1000 mg of phosphorus. Renal function was assessed by measurement of iothalamate and creatinine clearances at intervals of 3 to 6 months, and the patients were followed for a minimum of 12 months. Results demonstrated that dietary restriction of protein and phosphorus can retard the progression of renal failure in patients with IDDM who have nephropathy. 1 figure. 3 tables. 38 references. (AA-M).

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Role of Parenteral Nutrition in Inflammatory Bowel Disease, Acute Renal Failure, and Hepatic Encephalopathy Source: International Journal of Technology Assessment in Health Care. 6(4): 655-662. 1990. Summary: This article reviews the evidence concerning efficacy and safety of the use of parenteral nutritional support (also called total parenteral nutrition or TPN) in three clinical situations: as a primary therapy for patients with inflammatory bowel disease, for patients with acute renal failure, and for patients with hepatic cirrhosis resulting in encephalopathy. For each of the three situations, the rationale, efficacy, safety, and

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recommendations for using TPN are given. The authors conclude that the true value of parenteral nutritional support in these three clinical indications remains unknown. It is possible that future clinical trials will demonstrate the value of parenteral nutrition for these patients or for subgroups of these patients. 32 references. •

Current Issues and Future Perspectives of Chronic Renal Failure Source: JASN. Journal of the American Society of Nephrology. 13 (Supplement 1): S3-S6. January 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: This brief review article discusses some key issues of end stage renal disease (ESRD) and the prevention strategy for chronic progressive renal disease. The authors focus primarily on the issues in Japan and the United States because they represent and illustrate common problems pertaining to ESRD. Although some dialysis patients live longer than 5 to 10 years and are able to work and contribute to the society in which they live, others fare poorly and die within 2 to 3 years of going on dialysis. In addition to mortality (death), another issue surrounding ESRD is a rapidly aging dialysis population, in part related to the fact that the major proportion of new patients entering dialysis programs comprise people with type 2 diabetes. These problems require the worldwide nephrology community to rededicate itself to the retardation and prevention of the progression of all forms of renal disease. The authors discuss kidney transplantation, peritoneal dialysis, the complications of chronic dialysis, control of hypertension (high blood pressure), the role of dietary protein intake, and the potential impact of advances in molecular biology and genetic engineering. 2 tables. 8 references.

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Nutritional Status of Chronic Renal Failure Patients Following the Initiation of Hemodialysis Treatment. (editorial) Source: American Journal of Kidney Diseases. 40(1): 205-207. July 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: This editorial serves as an introduction to two related articles in this journal on the nutritional status of chronic renal failure (CRF) patients following the initiation of hemodialysis treatment. The author notes that the two papers have virtually identical titles and nearly the same conclusion; namely, that the initiation of chronic hemodialysis therapy in incident CRF patients is associated with improvement in nutritional status. The author discusses how these observations are important in a number of areas, including the predialysis management of chronic renal (kidney) insufficiency, when to initiate hemodialysis, subsequent nutritional status of patients on hemodialysis, and the influence of all of these on the long term outcome of patients with chronic renal insufficiency. The author concludes that until further information regarding nutrition, early start, dose and flux is obtained, these current studies certainly give credence to the National Kidney Foundation KDOQI recommendations on the initiation of dialysis therapy on malnourished patients with advanced chronic renal failure in whom other interventions have failed to result in nutritional improvement. 10 references.

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Oral Health in Children with Chronic Renal Failure Source: Pediatric Nephrology 18(1): 39-45. January 2003.

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Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: This study investigated oral health in 70 children (aged 4 to 13.6 years) with chronic renal (kidney) failure (CRF). Indices were recorded for dental caries (cavities), dental plaque, gingival (gum) inflammation, gingival enlargement, and enamel defects. Salivary urea, buffering capacity, and the oral streptococcal flora were determined for 25 of the children. A significantly greater proportion of the CRF children was caries free, 40 percent compared with 8.5 percent of the controls. The mean plaque score was significantly greater in the CF group for both the primary (12.7) and permanent dentition (22.0) compared with the controls: 5.3 and 15.5, respectively. Eight CRF children had gingival enlargement. Enamel defects affecting the permanent teeth were observed in 57 percent of the CRF children compared with 33 percent of the controls. The buffering capacity was significantly greater in the CRF group, pH 6.4 compared with the controls' pH 5.6. The mean salivary urea level was significantly greater in the CRF children. The isolation frequency of Streptococcus mutans was significantly greater from controls compared with the CRF children. The authors conclude that an integrated dental service needs to be developed with emphasis on toothbrushing to prevent gingival hyperplasia and periodontal disease after puberty in this population. 7 tables. 34 references.

Federally Funded Research on Renal Failure The U.S. Government supports a variety of research studies relating to renal failure. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to renal failure. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore renal failure. The following is typical of the type of information found when searching the CRISP database for renal failure: •

Project Title: A PROSPECTIVE STUDY OF CARDIOVASCULAR DISEASE IN ESRD Principal Investigator & Institution: Klag, Michael J.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-MAR-2005 Summary: (taken from the application) We are in the midst of an epidemic of end stage renal disease (ESRD). Treated ESRD has increased exponentially at an annual rate of 8% since 1973 when the U.S. ESRD treatment registry was initiated. Although it preserves

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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life, treated ESRD is associated with poor quality of life, considerable morbidity, and high mortality. The leading cause of death in treated ESRD patients is cardiovascular disease. The Principal Investigator is a leader in the epidemiology and prevention of renal disease who has an outstanding track record in patient-oriented research and mentorship. He has assembled and mentored a team of superb young investigators who are seeking to understand better the reasons for the increased risk of cardiovascular disease in patients with treated ESRD and less severe forms of renal disease. Mentorship is accomplished through a rigorous program of training in epidemiologic methods and intensive involvement in ongoing, federally-funded research projects. Tuition costs are covered by NIH sponsored training grants from NIDDK and NHLBI. The current proposal requests funds to increase the Principal Investigator's ability to mentor trainees and junior faculty by decreasing his substantial administrative commitment. The research projects described in this proposal are built on the foundation of the CHOICE Cohort Study, a national prospective study of over 1,000 incident cases of ESRD. A DNA and serum bank has been established at a central laboratory. Current research project conducted by trainees who will be mentored by the Principal Investigator as part of the current proposal include: 1. The role of emerging risk factors (Lpa, homocysteine, B vitamin, fibrinogen levels) in risk of CVD ESRD patients; 2. Identification of genes that increase risk of progression to ESRD; 3. Risk factors for vascular access failure. This information will lay the groundwork to prevent CVD in ESRD patients by providing the information needed for clinical trials. The Principal Investigator has a long history of successful mentoring in renal disease research. The proposed award will allow him to continue training the next generation of renal disease epidemiologists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADHERENCE AND ADJUSTMENT IN END-STAGE RENAL DISEASE Principal Investigator & Institution: Christensen, Alan J.; Professor; Psychology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 31-DEC-2003 Summary: (adapted from investigator's abstract): Increased quality assurance concerns associated with the Medicare End-Stage Renal Disease (ESRD) program underscore the need for research addressing the adaptation and quality of life of ESRD patients. Patients' levels of psychological adjustment and their degree of adherence with ESRD treatment regimen reflect two important criteria that are examined in the present continuation proposal. One central objective of the research involves identifying psychological characteristics that influence medical regimen adherence and emotional adjustment among patients treated with renal dialysis. This will be accomplished using a longitudinal study design that considers the effects of patient individual differences (i.e., coping style) and contextual differences among the available dialysis treatment modalities. A key aspect of the study involves the assessment of patients at an early stage of progressive renal insufficiency, before renal dialysis is clinically necessary. We hypothesize that adherence and adjustment will vary as a joint function of the type of dialysis prescribed and patient individual differences assessed at baseline. For example, we predict that patients' possessing a more active or vigilant style of coping will exhibit more favorable adherence when undergoing a self-administered dialysis treatment modality (e.g., continuous ambulatory peritoneal dialysis) but poorer adherence when receiving staff administered dialysis (e.g., center hemodialysis). A second objective involves identifying patient characteristics that are related to adherence to adjustment among renal transplantation patients. Initial psychosocial assessment will be conducted during the pre-transplant evaluation process. A set of hypotheses regarding

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psychological predictors of patient adherence and changes in emotional well being after transplantation will be tested in a prospective manner. For Example, we hypothesize that patients with a more active style of coping with health-related stress will exhibit better regimen adherence and better emotional adjustment than other transplant patients. We believe the proposed research will extend the role of psychological theory and practice in contributing to the care of ESRD patients. The knowledge generated will add to a growing body of literature that suggests psychosocial assessment information can be useful in the selection f the most beneficial renal treatment modality for a particular patient. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALGESIC USE AND THE RISK OF CHRONIC RENAL FAILURE Principal Investigator & Institution: Curhan, Gary C.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-AUG-1998; Project End 31-JUL-2004 Summary: Analgesic-associated nephropathy is potentially fatal and costly yet completely preventable as a cause of renal dysfunction. Retrospective studies have reported an increased risk of renal dysfunction associated with consumption of large amounts of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) but not aspirin. Since these analgesics are widely available and used, their association with renal dysfunction is particularly important. The primary objective of this study is to examine, prospectively, the association between chronic consumption of acetaminophen, aspirin and NSAIDs, and the risk of chronic renal dysfunction, defined as an increase in serum creatinine or a decrease in calculated creatinine clearance during the 5-year study period. From participants in two large female cohorts, the Nurses' Health Studies I and II (NHSI, NHSII), 3 groups of women will be identified, each comprised of 1150 participants (half from each cohort), who reported frequent use of acetaminophen, aspirin, or NSAIDs, and a fourth group of 1150 women who reported no use of these analgesics. Detailed information on dosage and duration of analgesic use will be obtained through supplementary questionnaires, to be mailed in the 01, 03, and 05 years, which have been shown to be reproducible. 4600 nurses will be enrolled at the outset and, after excluding women with prevalent renal disease and those who drop out, an expected 4000 will complete the study in the 05 year. The outcomes are: change in serum creatinine and calculated creatine clearance, measured at baseline and years 03 and 05 from all subjects. Mixed effects regression will be used to analyze the slope of renal function in the unexposed and exposed groups during the 5 year study period. For approximately 2000 subjects in NHSI, stored blood from 1989 will be used to perform the same analyses over a 13 year period. This study will provide: prospective data on change in renal function associated with chronic analgesic use; threshold levels of safe cumulative dose and duration of these analgesics; and population-based incidence rates and attributable risks of analgesic-associated chronic renal dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ASSESSING FUNCTIONAL OUTCOMES IN ADOLESCENT WITH ESRD Principal Investigator & Institution: Furth, Susan L.; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAR-2004

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Summary: provided by applicant): Dr. Furth is seeking the Small Grant Award to expand the study of clinical outcomes for children with end stage renal disease (ESRD) initiated under her KO8 Award DK 02586-01A1. With the support of the KO8 funding, Dr. Furth has completed her PhD in Clinical Investigation and has begun the transition to an independent research career. She has published a number of manuscripts using her training in epidemiology and clinical investigation: examining how clinical and socio-economic factors affect access to different treatment regimens for children with kidney failure, and how clinical experience with ESRD care for children affects treatment decisions. She has examined how poor growth, a crucial pediatric issue, affects mortality, hospitalization rates and educational achievement. She has also initiated a multi-center, cross-sectional study comparing functional outcomes/ health related quality of life (HRQL) for pediatric patients with chronic renal failure or ESRD treated with hemodialysis, peritoneal dialysis or transplant. Resources provided by the RO3 award will allow Dr. Furth to expand the multi-center study of health related quality of life in adolescents with ESRD to a prospective study. A prospective study will allow Dr. Furth to determine whether specific measures of health related quality of life are sensitive to clinical changes, as patients proceed from dialysis to transplantation. The supplementary funding of the R03, additionally will allow Dr. Furth to examine the link between clinical measures such as hematocrit, serum albumin, and dialysis adequacy (Kt/V) and functional outcome/HRQL. Furthermore, the prospective study will assess whether high risk behavior characterized by patterns of response on an adolescent health status questionnaire can predict non-compliance with therapy, increased hospitalization rates, acute rejection or transplant failure. The measures of functional outcome studied will include the Child Health and Illness Profile-Adolescent Edition, and the Child Health Questionnaire (Parent report). This research will provide an indepth analysis of a measure of functional outcome in children with ESRD, and will provide valuable information regarding optimal treatment choices for children with kidney disease. If assessments of high risk behavior predict increased rates of hospitalization, rejection or transplant failure, results of this study will allow identification of a high risk population of adolescents with ESRD, who can be targeted for early intervention and close follow-up to improve long term outcomes of care. The proposal addresses several priority areas for Clinical Research highlighted in the NIH Task Force publication, Research Needs in Pediatric Kidney Disease: 2000 and beyond. During this project, Dr. Furth will gain new skills in organizing and coordinating a prospective multi-center clinical research study. This experience will give Dr. Furth the tools she needs to develop into an independent clinical investigator in a nurturing academic environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BOLD MRI--APPLICATION TO INTRA-RENAL OXYGENATION Principal Investigator & Institution: Prasad, Pottumarthi V.; Evanston Northwestern Healthcare Evanston, Il 60201 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: Acute renal failure (ARF) is a syndrome that can be broadly defined as rapid deterioration of renal function resulting in the accumulation of nitrogenous wastes such as urea and creatinine. It is a major clinical problem and is a common hospital acquired syndrome with high mortality rates (approximately 50 percent). The pathophysiology of ischemic acute renal failure, the most common form of clinical ARF, is complex and not yet well understood. Based on previous studies on animal models, it is known that acute renal failure involves damage to the medulla which even under normal circumstances

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must function in an hypoxic environment. Hence an understanding of mechanisms that influence medullary hypoxia is important in the study of pathophysiology of ARF. To date, measurements of intrarenal oxygen tension have been made only with oxygensensitive microelectrodes implanted into the renal parenchyma of animals, a delicate and tedious procedure and impractical for human studies. BOLD (Blood Oxygenation Level Dependent) MRI has shown potential as a noninvasive method to assess on a regional basis the changes in the balance of oxygen supply and demand. We have previously demonstrated a strong correspondence between BOLD MRI measurements in vivo in human kidneys and earlier animal data using invasive microelectrodes. These studies provided evidence for the first time indicating a substantial degree of hypoxia in the human renal medulla. In this proposal, we will further evaluate this technique by comparing the BOLD MRI data obtained in an animal model with oxygenation measurements previously obtained with an invasive microelectrode technique. We will then apply the technique to both animal models and human subjects to derive new information about renal physiology/ pathophysiology especially related to ARF. The availability of a noninvasive method to evaluate regional oxygenation in kidneys in vivo should help to characterize therapeutic and protective mechanisms and thus lead to improved therapeutic and preventive measures for acute renal failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CA2+ HYPERPARATHYROIDISM

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Principal Investigator & Institution: Brown, Alex J.; Associate Professor; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2003 Summary: Parathyroid glands (PTGs) express a calcium-sensing receptor (CaR) that detects the concentration of extracellular calcium and signals the glands to secrete the proper amount of parathyroid hormone (PTH) to maintain normal calcium levels. The calcium-PTH relationship is sigmoidal and can be defined by four parameters: maximum PTH, minimum PTH, the midpoint of the curve (set-point), and the slope at the midpoint. The CaR levels are decreased in the hyperplastic PTGs of patients with secondary HPT (2oHPT) due to chronic renal failure (CRF), but the factors responsible are not known. The impact of this down-regulation on calcium sensitivity remains controversial. In vitro studies indicate decreased calcium sensitivity (elevated set-point) in parathyroid cells from CRF patients, but in vivo assessment of the set-point in CRF patients have yielded mixed results. Furthermore, in patients it is not possible to relate CaR levels to the four parameters of the calcium-PTH relationship. We have now observed a similar reduced CaR expression in hyperplastic PTGs of CRF rats. This model can be used to determine the role of decreased CaR in PTG hyperplasia and the abnormal calcium-PTH relationship, and to identify the factors that regulate the CaR. Definitive identification of the factors that directly control CaR levels requires an in vitro model with stable expression of the CaR. Traditional monolayer cultures do not respond to calcium. We have developed a unique parathyroid cell culture system that preserves the normal cellular architecture, allowing stable CaR expression and calcium response for several weeks. These cultures, which we refer to as pseudoglands or psGs, provide the best available model for studying the regulation off parathyroid cell CaR expression and provide a unique in vitro model t9o examine the effects in CaR levels on the calcium-PTH relationship. This grant presents an experimental approach that utilizes these in vivo and in vitro models to examine both the causes and effects of the downregulation of the CaR in renal failure. The specific aims are: 1. To define the

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relationships, temporal and spatial, between parathyroid gland hyperplasia and downregulation of the CaR in vivo. 2. To examine the effects of established therapies for uremic secondary hyperparathyroidism (phosphate restriction and vitamin D compounds) on CaR expression in uremic rats. 3. To determine the direct effects of potential regulators of CaR expression in vitro using the psG model. 4. To determine the effects of down-regulation of CaR on the calcium- PTH relationship and PTH expression in vivo and in vitro. These studies will provide new information about the effect of decreased CaR in CRF on the calcium-PTH relationship, define the factors responsible for the decrease, and test therapeutic strategies to correct the abnormality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCINEURIN IN CONGENITAL NEPHROPATHY Principal Investigator & Institution: Chen, Feng; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Congenital obstructive nephropathy is the most frequent cause of renal failure in infants and children. The molecular and cellular lesions leading to the congenital obstruction, however, are still largely undetermined. We hypothesize that calcineurin, a serine/threonine phosphatase, is indispensable for the normal development of the excretory system. We have generated a mouse strain with deletion of the CnB gene in a subset of Pax3 positive cells and their derivatives by Cre-mediated LoxP recombination. These mice have deletion of CnB in the excretory system, including the smooth muscle cells in the ureter. The affected mice have hydronephrosis and hydroureter and die from postnatal renal failure. We plan to further determine the nature, the spectrum, as well as the prenatal and postnatal progression of the congenital nephropathy in the mutants. Of particular interests, our previous experiments have demonstrated an indispensable role of calcineurin in the formation of the vascular smooth muscle layer around the major blood vessels. Based on this finding and our preliminary results, we further hypothesize that the disruption of calcineurin function in the ureteral smooth muscle or in the innervating nerves causes a defective peristalsis, leading to the obstructive nephropathy. To test this hypothesis, we will determine whether the mutants have anatomical or functional defects preventing effective peristalsis and will identify the causative cellular lesions. Finally, we will study the ontogeny of the urinary tract smooth muscle cells and the potential neuronal contribution to the congenital nephropathy. The Pax3Cre-CnB mutants we generated have defined genetic modifications and a consistent early onset congenital obstructive nephropathy leading to kidney failure. These mice will serve as a good animal model to study the causes of congenital obstructive nephropathy. Results from the proposed study will also enhance our understanding of the pyeloureteral peristalsis, the ontogeny of ureteral smooth muscle cells, and the role of calcineurin signaling in these processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARBOHYDRATE AND PROTEIN METABOLIC PATHWAYS Principal Investigator & Institution: Landau, Bernard R.; Professor of Medicine and Biochemistry; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-MAY-1978; Project End 31-MAR-2005 Summary: (Provided by applicant): Carbohydrate, protein and lipid abnormalities characterize diabetes mellitus. Long-term objectives are to develop and apply novel

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methods significantly advancing understanding of those metabolic processes and their regulation in physiological and pathological states in human, and particularly in diabetes. Advantage is taken of 2H2O use to quantitate the pathways followed. Methods have been introduced for carbohydrate and lipid. The major new goal is to develop and apply a method for quantitating protein metabolism. The method for quantitating carbohydrate metabolism will also be further extended. Focus then is on 1) the quantitation of protein synthesis and proteolysis; 2) the contribution to glucose production of gluconeogenesis whose increase in diabetes has been related to the degree of hyperglycemia and 3) the extent of simultaneous hepatic glycogen synthesis and breakdown, called glycogen cycling, which could help explain decreased liver glycogen content found in type 2 diabetes and exacerbate hyperglycemia on glucose ingestion. There are 4 specific aims: 1) To develop and apply a method for quantitating the extent transaldolase reactions contribute to estimates of gluconeogenesis; 2) To evaluate the validity of a method using glucose isotopomers, introduced as a simple method to measure the contribution of gluconeogenesis, in comparison with 2H2O use; 3) To develop a method for quantitating glycogen cycling in the fed state by measuring, along with the rate of hepatic glycogen deposition on glucose intake, how much of the glycogen is formed directly from the glucose, how much from three carbon compounds, and how much from glycogen that is reconverted to glycogen, i.e. glycogen cycling; 4) To develop a method to estimate protein synthesis from labeling of protein by 2H2O, and proteolysis from loss of that label. Initial application of this method will be to renal failure patients undergoing hemodialysis, in whom ingested 2H2O can be removed by dialysis to readily follow loss of incorporated label without continued synthesis of labeled protein. Application first to the renal failure state is done with recognition that nephropathy is a major complication in the diabetic and the potential benefit of a simple method for evaluating the effects of the therapeutic approaches on protein dynamics in that condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIAC OSTEODYSTROPHY

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Principal Investigator & Institution: Kestenbaum, Bryan R.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-JAN-2008 Summary: (provided by applicant):Cardiovascular disease (CVD) accounts for nearly half the mortality, and extensive morbidity, among patients with renal failure. Comorbid illness and traditional cardiac risk factors do not fully explain the epidemic proportion of CVD observed among dialysis patients. Secondary hyperparathyroidism (SHPTH) is a disorder of calcium metabolism found in renal failure that has been linked to cardiovascular (CV) pathology in experimental models of disease. Clinical evidence relating SHPTH with CV outcomes is limited.The three major aims of the proposed study are 1) to estimate the relationship between serum markers of SHPTH and clinical CV outcomes among patients with renal disease, 2) to estimate the relationship between medications regimens used to treat SHPTH and cardiovascular outcomes, and 3) to recruit a new cohort of dialysis patients to participate in pilot studies and serve as a foundation for future research into the relationship between SHPTH and clinical CVD. Two parallel activities will be conducted to address out scientific aims. First, we will study an established cohort of dialysis patients from the United States Renal Database System (USRDS) and an established cohort of chronic renal insufficiency (CRI) patients from the Veterans' Administrations' Consumer Health Information and Performance

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Sets (CHIPS) database. The serum markers of interest are intact PTH, calcium, and phosphate. Medication exposures of interest are dosages of phosphate binders and calcitriol. Second, we will recruit a new cohort of 100 dialysis patients from the Northwest Kidney Center and the Veterans' Administration Medical Center dialysis centers.We will ascertain traditional and novel serum markers of SHPTH among our patient cohorts, and then follow them for the development of subsequent CV related hospitalizations. The primary outcome is time to first cardiovascular hospitalization or cardiovascular death. The proposed study aims to shed light on the relationship between a common renal related metabolic disorder and the epidemic burden of CVD found among this patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR CALCIUM TRANSPORT IN URINARY EPITHELIA Principal Investigator & Institution: Friedman, Peter A.; Professor; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-MAR-2003 Summary: The long-term objective of our work is directed toward a complete understanding of the cellular mechanisms and regulation of calcium transport by renal tubular epithelial cells. Although most calcium absorption proceeds in proximal tubules, distal tubules are the site of the physiological regulation of calcium transport by parathyroid hormone (PTH), calcitonin and vitamin D3. The specific aims of the present proposal are to: 1) characterize the mechanism of calcium entry across apical plasma membranes of distal convoluted tubule (DCT) cells; 2) evaluate the participation and regulation of Na+/Ca2+ exchange in mediating calcium efflux; and, 3) define the signaling pathways activated by PTH and calcitonin in DCT cells, and to examine the coordinate regulation of PTH-dependent calcium transport by 1,25(OH)2 vitamin D3 and estradiol. We identified and partially characterized a novel calcium channel that mediates calcium entry. To acquire additional information about these channels we will: 1) characterize the properties of these channels with regard to their ion selectivity, pharmacologic sensitivity and voltage- dependence; 2) determine the regulation of these calcium channels by protein kinases; 3) define the participation of G-proteins in regulating calcium entry channels; and, 4) identify and clone calcium channel transcripts. Extrusion of calcium across basolateral plasma membranes of distal tubules is mediated by Na+/Ca2+ exchange and by /ca2+-ATPase. Pilot studies suggest that Na+/Ca2+ exchange is the dominant efflux mechanism in DCT cells. We will: 1) Test the hypothesis that thiazide diuretics can inhibit Na+/Ca2+ exchange; and 2) Characterize the stimulatory effects of PTH on Na+/Ca2+ exchange. Calcium transport in distal nephrons is regulated by PTH, calcitonin and 1,25(OH)2 vitamin D3. The following studies will evaluate the mechanism mediating the hormonal regulation of calcium transport in DCT cells. The goals of these experiments are to: 1) Characterize the signaling pathways with particular regard to the phospholipases responsible for activating PKA and PKC and characterize the temporal sequence in which PKA and PKC are activated. We will test the hypothesis that PTH and calcitonin activate PKC via phospholipase D. 2) Identify the mechanism by which PTH activates C1- channels, a primary event in membrane hyperpolarization and stimulation of calcium transport in DCT cells. We will test the hypothesis that these chloride channels are regulated by the PKA limb of the PTH-activated signaling pathway. 3) Examine the regulation of vitamin D3 and estradiol accelerate PTH dependent calcium transport by up-regulating PTH receptor expression. The specific aims will be achieved by applying single cell fluorescence, patch clamp, tracer flux measurements, biochemical and molecular

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techniques to a DCT cell line that we developed, which expresses an appropriate phenotype. In selected studies, primary cell cultures of proximal or distal tubule cells will be used to verify results in transformed cells or as controls. All procedures are established in our lab. Results from the proposed experiments will provide new information on the mechanism and regulation of calcium transport in the kidney under normal conditions, but also in calcium-wasting syndromes including hyperparathyroidism, renal failure, osteoporosis and malignancy- associated hypercalcemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLONAL SELECTION IN DIABETIC NEPHROPATHY Principal Investigator & Institution: Lenz, Oliver; Medicine; University of MiamiMedical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The prevalence of diabetic nephropathy,the leading cause of end-stage renal failure, has been rising over the past years; despite recent advances in the management of diabetic patients.We have previously shown that the susceptibility to develop progressive glomerulosclerosis varies between mouse strains as it does between different ethnic groups. We identified both sclerosis-prone (ROP) and sclerosis-resistant (C57BL/6) mouse strains, and found that mesangial cells from these strains respond differently to glucose. Our preliminary data show that different subpopulations exist among mesangial cells isolated from sclerosis prone mice. They are characterized by a different length in the d(CA) repeat in the MMP-9 promoter, which recently has been linked to the risk of developing diabetic nephropathy. Rather than using this dinucleotide repeat for linkage studies, we propose that it can be used as a marker for mesangial cell sub-populations. In ROP mesangial cells, we identified single cell clones with d(CA)20 and d(CA)24 repeats. After exposure to high glucose levels, all mesangial cells isolated from ROP mice contained the d(CA)24 dinucleotide repeat. No heterogeneity in the d(CA) dinucleotide repeat length was detected at baseline in mesangial cells isolated from sclerosis-resistant C57BL/6 mice, and no change was observed after exposure to high glucose levels. This led us to propose that in susceptible individuals, diabetes mellitus leads to the clonal expansion of one of the mesangial subpopulations responsible for progressive glomerulosclerosis, and that the length of the d(CA) repeat in the MMP-9 promoter is a suitable marker to distinguish the different sub-populations. We will test the hypothesis that exposure to high glucose levels leads to a clonal selection in mesangial cells cultured from sclerosis-prone ROP mice. We will analyze the differences in gene expression that characterize sub-populations of mesangial cells in low and high glucose levels. The long-term goal of our proposal is to characterize the role of clonal selection in glomerular disease, and identify new targets for screening, prevention, and intervention in the pathogenesis of diabetic nephropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOKINE GENE POLYMORPHISMS IN ACUTE RENAL FAILURE Principal Investigator & Institution: Jaber, Bertrand L.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Acute renal failure (ARF) is a serious complication in hospitalized patients, with an incidence of 5-10%, and mortality exceeding 50% among those who require dialysis. Pro- and anti-inflammatory cytokines play a pivotal

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role in the host inflammatory responses that mediate the severity of ARF. Yet, the importance of susceptibility genetic factors such as cytokine gene polymorphisms has remained largely unexplored. The principal investigator (PI) has designed a rigorous training program that will provide him with the necessary skills, experience, and opportunities to develop into an independent investigator in the field of inflammatory genetic markers and epidemiology of acute renal failure. He will obtain a Masters of Science in Clinical Care Research, participate in projects utilizing a broad range of study designs for clinical research, and carry out an original research project from its inception to completion. His mentors have extensive experience in clinical and laboratory investigation of ARF and clinical care research in Nephrology. Single nucleotide polymorphisms (SNP) in the promoter region of the human tumor necrosis factor-alpha (TNF-alpha) (position -308), interleukin-6 (IL-6) (position -174) and interleukin-10 (IL-10) (position -1082) genes affect transcriptional activity and have functional relevance. These genetically determined differences might influence variations in host inflammatory responses to stressful stimuli. The hypotheses to be investigated are that SNP involving these cytokines predetermine the severity of ARF, and are independent risk factors for adverse clinical outcomes. The specific aims are to: 1) characterize the frequency of these pro- (TNF-alpha and IL-6) and anti-inflammatory (IL-10) cytokine gene polymorphisms in a cohort of patients with ARF; 2) Examine their relationship to leukocyte production and plasma levels of cytokines as well as clinical and laboratory variables; and 3) Evaluate whether these genetic markers individually or in combinations, predict adverse clinical outcomes, mainly dialysis requirement and mortality. The research project is achievable and promises to provide new insights into the importance of genetic markers as novel susceptibility factors for severity of disease in ARF. The results may help identify target patients who may benefit from anti-cytokine therapies. The PI has assembled a team of scientists to assist in the conduct of the project, and convened and internal and external scientific advisory committee to monitor his progress. The proposed training program and research project will prepare him for a career as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIABETIC NEPHROPATHY Principal Investigator & Institution: Mauer, Michael S.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: These continuation studies focus on large pancreas (PTx) and kidney (KTx) transplant populations of type 1 diabetic (D) patients (pts) in order to better understand diabetic nephropathy (DN), the leading cause of renal failure. Objectives are: (a) to determine whether PTx can more readily arrest or reverse the early vs. the more established lesions of DN; (b) to continue studies of renal structural-functional relationships in DN, with emphasis on the multifaceted pathologic DN lesions, including glomerular, vascular, interstitial lesions and glomerular-tubular connections; (c) to continue studies of DN natural history and the role of renal biopsy in predicting outcome; (d) to quantitate and understand the basis of atubular glomeruli (AG) in DN; (e) to elucidate glomerular (glom) epithelial cell abnormalities in DN; (f) to study the glom extracellular matrix abnormalities of DN; (g) to study the recurrence of DN in the KTx; (h) to study the molecular/genetic basis of DN and develop cellular markers of DN risk; (i) to determine the long-term (10-15 yr) structural consequences of cyclosporine (CSA) on the 'native kidneys of PTx recipients; and (j) to determine the shorter-term (5 yr) consequences of Prograf on the native kidneys of PTx recipients and compare these

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with those seen after 5 years of CSA treatment. Together, these studies will help to elucidate the pathogenesis and natural history of DN, unravel some of the molecular and genetic aspects of this disease, describe the dynamics of DN reversal in PTx pts, and recurrence in KTx pts and expand our knowledge of the nephrotoxic effects of calcinosis inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIPYRIDAMOLE IN VASCULAR ACCESS FOR HEMODIALYSIS Principal Investigator & Institution: Himmelfarb, Jonathan; Professor; Maine Medical Center 22 Bramhall St Portland, Me 04102 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: The long-term objective of this proposal is to establish whether or not the use of dipyridamole is efficacious in improving the function of expanded polytetrafluoroethylene (ePTFE) grafts used for dialysis access in patients with end stage renal disease on chronic hemodialysis therapy. Currently, there are over 170,000 patients in the US on chronic hemodialysis therapy. For these patients, problems with vascular access patency have been called the "Achilles Heel" of the dialysis procedure. Furthermore, the development of ePTFE graft stenosis and thrombosis reduces the quality of delivered dialysis therapy and increases the infection risk for patients on dialysis. Maintaining vascular access patency costs approximately $7,871 per hemodialysis patient per year at risk with an estimated annual global cost of more than one billion dollars. Recent evidence suggests that in almost all cases, ePTFE graft thrombosis occurs only after the development of a stenosis either at the graft vein anastomosis or more distally in the vein. These venous stenoses occur because of a pathological process known as intimal hyperplasia. Recent evidence from a small, single-center, prospective, randomized, placebo-controlled clinical trial has suggested that dipyridamole may reduce the rate of ePTFE graft thrombosis in chronic hemodialysis patients. The mechanism of dipyridamole efficacy may be by inhibiting vascular smooth muscle cell proliferation and thereby reducing the development of intimal hyperplasia and associated venous stenoses. The specific aims of this proposal are: l) To investigate the efficacy of dipyridamole in preventing the development of anastomotic and venous stenoses in patients on chronic hemodialysis with ePTFE grafts; and 2) To investigate the efficacy of dipyridamole in preventing the development of thrombosis in patients on chronic hemodialysis with new ePTFE grafts. In order to answer the Specific Aims, the proposed study design is a randomized, prospective, double-blind, placebo-controlled, parallel group clinical trial. Patients on chronic hemodialysis therapy who require a new prosthetic ePTFE graft will be randomized to receive either dipyridamole or placebo for a period of 12 months after enrollment or until ePTFE graft failure. Enrolled patients will undergo serial monitoring of vascular access blood flow, known to be a physiologic predictor of impending vascular access failure, with clinically indicated interventions to prevent vascular access failure. The study design will test the null hypothesis that dipyridamole does not affect the development of either venous stenosis or thrombosis in new ePTFE grafts in hemodialysis patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF CLOPIDOGREL ON EARLY PATENCY OF AV FISTULAE Principal Investigator & Institution: Dember, Laura M.; Associate Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118

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Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Purpose: The objective of this proposal is to design randomized, controlled rnulticenter trials evaluating interventions to increase the survival of vascular access for hemodialysis and to form a collaborative network of clinical centers and a data coordinating center to perform such studies. Specific Aims: This application has two specific research aims: l) To determine whether the administration of clopidogrel for four weeks beginning on the day prior to native fistula creation reduces the rate of early fistula failure compared with placebo, and 2) To create a Collaborative Boston Area Clinical Center with the patient population and clinical and research expertise necessary to conduct the series of studies of the Hemodialysis Vascular Access Clinical Trials Consortium. Background: Maintenance of vascular access for hemodialysis is one of the major challenges in the care of the hemodialysis patient. Access-related problems are among the most frequent reasons for hospitalization in the end-stage renal disease (ESRD) population, and the cost of vascular access placement and repair in the United States currently exceeds $700 million per year. Despite the well-established advantages of native arteriovenous fistulae (higher unassisted potency rates and lower rates of infection) compared to grafts or catheters, the proportion of the United States hemodialysis population with a native fistula is low. An important factor contributing to this low prevalence is early thrombosis of newly created fistulae. Several small studies of antiplatelet agents have shown a reduction in early thrombosis rates of native fistulae, but have not been powered sufficiently to definitively demonstrate a benefit. Methods: Patients with chronic renal failure who are scheduled to undergo creation of a native fistula and are without contraindication to antiplatelet therapy will be randomized to receive either placebo or clopidogrel 75 mg daily beginning the day prior to fistula creation and continuing for an additional 4 weeks. The primary outcome measure will be attainment of a fistula suitable for dialysis without any radiologic or surgical intervention. The secondary outcome measures will be: l) fistula potency at completion of study drug, and 2) attainment of a fistula suitable for dialysis including those fistulae modified radiologically or surgically. The Boston Area Clinical Center will be comprised of five facilities with greater than 600 patients currently on hemodialysis and large preESRD populations from which to draw study subjects. These study sites have extensive successful experience in multicenter clinical trials in ESRD. The Boston Area Clinical Center is organized to efficiently collaborate on the series of clinical trials conducted by the Hemodialysis Vascular Access Clinical Trials Consortium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF SHIGATOXIN-1 ON BRAIN ENDOTHELIAL CELLS Principal Investigator & Institution: Kohan, Donald E.; Chief, Division of Nephrology; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from the application) HUS is the leading cause of acute renal failure in children and is characterized by renal injury, microangiopathic hemolytic anemia, and thrombocytopenia. Although the kidney is an initial target in HUS, those patients who die from the disease do so primarily from brain, not renal, involvement. There is, however, very little understanding of how the central nervous system is affected in this disorder. HUS is associated with enteric infection by Shiga toxin (Stx) producing E. coli. The toxin binds to cells expressing a specific glycosphingolipid cell surface Stx receptor (Gb3) whereupon it may exert a variety of effects, including inhibition of protein synthesis, induction of apoptosis, regulation of vasoactive factor production, and others. Generally, these studies have focused on cells thought to be

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primary targets in HUS, namely, renal cells. Very little work, however, has been done on how Stx affects the brain. Preliminary studies from our laboratory indicate that human brain microvascular endothelial cells (HBEC) might be targets of Stx action. Further, these studies suggest that HBEC may respond to Stx and factors likely to be present in the setting of HUS in highly unique manner. Based on these findings, the following hypothesis has been formulated: Unlike renal endothelial cells, HBEC are not normally sensitive to Stx. Soluble or cell-associated members of the inflammatory cytokine superfamily, derived from circulating white blood cells or endothelial cells themselves, cause massive upregulation of Stx responsiveness in HBEC. Such upregulation leads to enhanced white blood cell and possibly platelet adhesion, endothelial cell apoptosis and necrosis, and altered vasoactive factor production. The unique responsiveness of HBEC to cytokine upregulation of Stx-1 sensitivity may provide the basis for therapeutic interventions aimed at blocking cytokine actions on the brain. Accordingly, the specific aims are: 1) Determination of HBEC sensitivity to the cytotoxic and protein synthesis inhibitory effects of Stx-1; 2) Determination of inflammatory factor regulation of the cytotoxic effect of Stx-I in HBEC; 3) Determination of the source(s) of inflammatory cytokines that affect HBEC responsiveness to Stx-1, focusing on HBEC and circulating white blood cells; and 4) Determination of the effects of Stx-1 on HBEC that could lead to CNS dysfunction in HUS, including mechanisms of cytotoxicity, regulation of vasoactive factor production, and modulation of platelet adherence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF VASOACTIVE DRUGS ON PERFUSION IN SEPTIC SHOCK Principal Investigator & Institution: Murray, Patrick T.; Anesthesia and Critical Care; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): This Mentored Patient-Oriented Research Career Development Award application requests support (or a proposal which includes mentorship by an experienced investigator, multidisciplinary support from the Chairs and faculty of several Departments. formal training in an NIH-funded Clinical Research Training Program. and a research project dissecting the regional and systemic effects of traditional and novel vasoactive drugs in critically ill patients with septic shock. Sepsis. the systemic inflammatory response to infection. may lead to refractorv hypotension (septic shock) and multiple organ system failure (MOSF). Despite increased cardiac output and oxygen delivery, death often ensues from refractory hypotension or subsequent MOSF. Standard indicators of adequate tissue perfusion which are used to titrate therapy in hypovolemic or cardiogenic shock are unreliable in hyperdynamic septic shock. Rational septic shock therapy would preferably be guided by targeted interventions tc? optimize end-organ perfusion and function, and reverse detectable tissue hypoperfusion. The primary end-organ index of adequate perfusion used in current clinical practice is renal perfusion and function. The effects of vasoactive drug therapy on renal perfusion and function are reliably quantifiable with sophisticated existing technology. This application seeks to determine the regional circulatory effects of restoring vascular contractility with standard exogenous catecholamines and the novel use of exogenous vasopressin, alone or in combination, in septic humans, focusing on renal perfusion and function. We will also examine the systemic and regional effects of targeted vasodilator therapy with fenoldopam (a novel dopaminergic agonist) in septic humans, alone or in combination with the aforementioned vasoconstrictors. Specifically, we will address the hypotheses that: 1) Addition of inotropic support (b-

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adrenoceptor stimulation) to intravenous fluids alone, or in combination with pure vasopressor therapy (a-adrenoceptor stimulation), improves renal perfusion and function in patients with sepsis or septic shock. 2) Titration of vasopressor therapy to a mean arterial pressure above the lower renal autoregulation threshold improves renal perfusion in patients with vasopressor-dependent septic shock. 3) Vasopressin therapy restores septic vascular contractility, augments vasopressor-responsiveness, reverses hypotension. and improves systemic and renal perfusion in human subjects receiving standard therapy for sepsis or septic shock. 4) Septic renal vasoconstriction is reversed, and renal perfusion and function improved, by selective renal vasodilator therapy. The overall aim of these experiments is to develop rational pharmacologic regimens and strategies for hemodynamic support in septic shock. focusing on prevention and management of septic acute renal failure, as a surrogate endpoint to optimize systemic perfusion in hyperdynamic states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTHELIAL CELL INJURY: QUANTIFYING ITS ROLE IN ISCHEMIC ACUTE RENAL FAILURE Principal Investigator & Institution: Molitoris, Bruce A.; Professor of Medicine and Chief,; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Taken directly from the application) Ischemia/reperfusion injury (IRI) is a major contributor to the organ damage that results in acute renal failure, one of the major causes of morbidity and mortality in hospitalized patients in the United States. We propose endothelial cell injury during the initiation phase of ARF (anoxia resulting from decreased vascular perfusion of the organ) occurs and is compounded thereafter by continued hypoxia in the cortical medullary region of the kidney. This results in further endothelial cell injury mediating epithelial cell injury and worsening organ dysfunction. Many factors are known to be involved in ischemia/reperfusion injury, but considerable data point to an important role for endothelial cells, as agents of injury in the kidney as well as other organs. Furthermore there is evidence that actin cytoskeletal alterations, occurring during cellular ATP depletion, mediate many of the structural and functional changes known to occur in ischemic cells. However, documentation of endothelial damage in the kidney is lacking. Therefore, we propose to test our hypothesis using an experimental model of ischemia/reperfusion injury in the mouse, and to determine the extent of initial and subsequent ischemia-induced endothelial injury and endothelial actin alterations. We will exploit recent advances in gene therapy and imaging technologies to image endothelial cell dynamics in live animals whose endothelial cells have been labeled with green fluorescent protein (GFP). We will also use this system to investigate the effect of ischemia/reperfusion on the dynamics of renal microvascular blood flow. Finally we will isolate GFP labeled microvascular endothelial cells and study the effects of ATP depletion on the actin cytoskeleton, actin depolymerizing factor (ADF) and expression of ADF using an adenoviral system to express a GFP-ADF chimera in cultured endothelial cells and in in vivo studies. These studies will provide a better understanding of the clinically important phenomenon of ischemia/reperfusion injury, and provide new methods for testing potential therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOTHELIAL GB3 SPECIES INVOLVED IN HUS PATHOGENESIS Principal Investigator & Institution: Newburg, David S.; Biochem & Molecular Pharmacol; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (adapted from the application) Acute renal failure and central nervous system (CNS) injury are life-threatening complications of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura (HUS/TTP). Survivors of HUS/TTP sometimes suffer irreversible damage. This application tests two hypotheses regarding the binding and toxicity of Shiga toxin (Stx) of enterohemorrhagic Escherichia coli (EHEC) to renal and cerebral endothelial cells, a critical process in HUS/TTP pathogenesis: (1) Metabolic regulation of globotriaosylceramide (Gb3) and galactosyl Gb3 (Gal Gb3), the glycolipid receptor(s) for Stx in endothelial cells, is central to HUS/TTP. (2) Binding to specific Gb3/GaI Gb3 molecular species is responsible for biological activity of Stx. Specific fatty acid moieties in the ceramide portions of Gb3/GaI Gb3 have been shown to influence Stx binding, and specific Gb3 species relate more strongly than total Gb3 to Stx-induced injury of endothelial cells from human saphenous veins. Using the cells most relevant to HUS/TTP, human glomerular endothelial cells (hGEC) and human cerebral endothelial cells (hCEC), investigations will (1) Isolate and measure individual Gb3/GaI Gb3 species in hGEC and hCEC cultures incubated with and without TNF-alpha and IL1-beta. (2) Determine which Gb3 and Gal Gb3 species relate to Stx1 and Stx2 toxicity in cytotoxin-stimulated and unstimulated cultures and to Stx binding to cells. (3) Define the metabolic pathways that synthesize the individual molecular species of Gb3/GaI Gb3 in response to TNF-alpha or IL1-beta stimulation by selectively inhibiting previously described pathways. Determine which UDPgalactose: lactosylceramide alpha1, 4 galactosyltransferase isozymes control this synthesis. Elucidation of the different sensitivities of renal and cerebral cells to Stx may explain differences in the pathogenesis of renal and CNS disease in HUS/TTP. The detailed description of the expression of these endothelial cell Stx receptors will potentially lead to development of precisely targeted therapies that can reduce Stx toxicity and these devastating effects of HUS/TTP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETIOLOGY OF NEPHROPATHY AND HYPERTENSION IN AASK PATIENT Principal Investigator & Institution: Lipkowitz, Michael S.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (adapted from the application) We will study the etiology of hypertension and nephropathy in the majority of the 1094 African-American patients in the AfricanAmerican Study of Kidney Disease in Hypertension (AASK). The AASK study is an NIH sponsored clinical multicenter trial comparing the effect of two levels of blood pressure control and three antihypertensive regimens on progression of hypertensive nephropathy in African Americans. There is a disproportionate number of African Americans with hypertensive target organ damage, suggesting a genetic susceptibility in this population; paradoxically, few studies have been performed to evaluate such genetic predisposition to disease in this high risk population. The patients of the AASK study offer a unique opportunity to prospectively determine the genetic factors involved in hypertension and hypertensive target organ damage within a high risk and under-

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studied population. The proposed studies will immortalize white blood cells from patients to provide a renewable source of tissue and DNA from this unique study group, and follow two approaches in assessing the etiology of hypertension, nephropathy, and their sequelae: 1. Studies are proposed to determine whether polymorphisms in candidate genes for hypertension, renal failure, and cardiac disease, including renin-angiotensin system genes, insulin resistance (beta3-adrenergic receptor and lipoprotein lipase) genes, Liddle's syndrome (beta and gammaENaC) genes, and others are related to hypertension or renal failure, severity/rate of progression of renal disease, severity/refractoriness of hypertension, electrocardiographic left ventricular hypertrophy, cardiovascular morbidity and mortality, and overall morbidity and mortality. 2. Additional studies will employ a new technique, mapping by admixture linkage disequilibrium (MALD), which uses the linkage disequilibrium caused by recent admixture of founder populations to localize genes linked to a particular phenotype within a 5-20 centiMorgan region in a genome-wide screen. By utilizing microsatellite markers from the carefully phenotyped patients of the AASK Study it should be possible to identify regions of interest containing genes associated with hypertension, renal failure, and the outcomes described above for candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FETAL ORIGINS OF ADULT HYPERTENSION IN MICROSWINE Principal Investigator & Institution: Bagby, Susan P.; Professor of Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: A growing body of human epidemiologic evidence links intrauterine growth retardation (IUGR) and adult "Syndrome X": hypertension, obesity, diabetes, coronary artherosclerosis, and risk of renal failure. In preliminary studies in microswine, maternal isocaloric protein restriction (0.5% vs. 14%) during nephrogenesis (last 1/3 gestation +3 weeks post- natally) yields IUGR at 3 weeks, rapid catch-up growth to 123% of control body weight (overweight), adult hypertension, reduced nephron number by histology, and normal GFR suggesting single-nephron hyperfiltration. Renal cortical AT1 and AT2 receptors by quantitative autoradiography are abnormal in both 3week and 6-month old offspring of low-protein sows but in unique ways. We hypothesize that excess appetite/body image size generate excess protein load for the low number of nephrons, driving sustained intrarenal renin/AngII (RAS) activation to achieve nitrogen balance via single-nephron hyperfiltration. This RAS response is predicted to amplify the Na retention and extracellular fluid volume (ECV) excess expected with fewer nephrons, yielding hypertension. In a microswine model of maternal protein restriction/IUGR, studies in offspring will address: 1) whether IUGR modifies the activation state of circulating vs. intrarenal RAS at key developmental stages (preterm; 2-weeks postnatal; 3-month pre- hypertensive juvenile; and 6-month adult), including mRNA, protein, and activity levels for renin, angiotensinogen, ACE, AngII, and AT1/AT2 receptors at Low-Protein vs. Normal-protein offspring on ad lib normal diet; 2) whether IUGR enhances postnatal homeostatic responses of blood pressure (BP), ECV, Na balance, and circulating vs. intrarenal RAS components in vivo to dietary sodium manipulation to AngII blockade; 3) whether IUGR amplifies AT1 signaling efficacy in vitro in cultured vascular smooth muscle at each developmental stage; and 4) whether global caloric restriction to limit adult bodyweight to 75% of Normal-protein controls in IUGR offspring attenuates adult BP, body fat mass, ECV, and intrarenal RAS components. Results are relevant to etiologic mechanisms of

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hypertension and to the preventive management of IUGR-exposed children at risk for adult cardiovascular and renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: G PROTEIN REGULATION OF GLOMERULAR EPITHELIAL CELLS Principal Investigator & Institution: Denker, Bradley M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): The podocyte is a highly specialized epithelial cell that forms multiple foot processes along the glomerular capillary basement membrane. The "junction" between foot processes (slit diaphragm) is critical to selective glomerular permeability. Podocyte injury is a hallmark of glomerular disease and is prominent early in the course of diabetic nephropathy and other causes of chronic kidney disease. Loss of slit diaphragms results in altered glomerular hemodynamics, proteinuria and progressive renal failure. The slit diaphragm shares many features of typical epithelial cell junctions, yet little is known about how these structures are regulated. Based upon our work in MDCK cells, we hypothesize that G proteins are likely to be critical molecules for regulating slit diaphragm structure/function. Ga12 through interactions with ZO-1 is likely to regulate Rho and/or Src pathways and the actin cytoskeleton in podocytes. In Aim 1, the interaction of ZO-1 and Ga12 will be studied in mouse glomeruli and cultured podocytes by confocal and immunoelectron microscopy and by coprecipitations (immuno- and GST fusion proteins). Cultured podocytes will be used to define signaling from Ga12 to Rho and/or Src kinase pathways. A combination of inhibitors and stable podocyte cell lines expressing active and inactive mutants of Ga12, Rho, and Src will be established to characterize functional effects on the barrier (paracellular flux assays) and changes in structure (by confocal localization of signaling (Ga12, Rho, Src) and slit diaphragm (ZO-t, actin, nephrin)) proteins. In Aim 2, animal models will be developed to characterize these signaling pathways in-vivo. Two approaches will be utilized; A "knock in" of active Ga12 (Q229L) and transgenic podocyte specific expression of Q229La12. A targeting construct for the "knock in" is nearly complete, and the mouse podocin (NPHS2) promoter wil be used for targeting activated Ga12 to the podocyte. Animals will be studied biochemically for evidence of renal disease (proteinuria, creatinine) and morphologically by light and electron microscopy at various ages. Results from studies in cultured podocytes will determine future transgenic models (Rho, Src). These studies will reveal novel insights into regulation of podocyte structure and function. The animal models will extend these findings to in-vivo systems where novel treatment strategies for common podocyte diseases (diabetes and others) can be tested. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE DISCOVERY IN HERITABLE RENAL HYPODYSPLASIA Principal Investigator & Institution: Lozanoff, Scott; Anatomy & Reproductive Biology; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Renal hypodysplasia (RHD) is a congenital disease that results in abnormally small and dysplastic kidneys. RHD is associated with chronic renal failure since the excretory portion does not differentiate properly and renal tubules progressively distend due to decreased filtration efficiency. Genes directing dysmorphogenetic events in RHD remain obscure. This project utilizes a radiation

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induced mutation in the 3H1 mouse called Brachyrrhine (Br) that inherits RHD as an autosomal semidominant trait. The overall goal of this project is to determine the genetic basis of RHD using Br as a model. Previously, Br was mapped to the distal portion of murine chromosome 17 (chr17). The first specific aim of this project is to undertake a high resolutioin microsatellite linkage analysis of distal chrl 7 to isolate a 100 - 500 kilobase region utilizing a large back cross mouse DNA sample followed by an in silico analysis of the candidate gene region using Celera and Sanger Gene Discovery databases. The second aim is to screen renal tissues of mutant and normal embyos at gestational days 13 and 14 for candidate gene expression using Northern blot analysis. It is expected that a gene deletion will be identified since the mutant phenotype and inheritance pattern is consistent with a radiation induced doubled stranded break and segment deletion. If a deletion is indicated, renal mRNA expression patterns in the mutant will be compared to corresponding normal renal tissue using RT-PCR and in situ hybridization, while associated protein analysis will utilize immunohistochemical methods. Specific aim 3 will sequence each exon in the candidate region using 3H1+/'+ and Br/Br DNA samples. Thus, the mutation in 3H1 Br will be determined even if a deletion is not found in Specific Aim 2. Additional methods will be utilized including SSCP and heteroduplex analysis to identify mutations in exons that may have been missed. As a result of this project, the gene responsible for RHD in 3H1 Br/Br mice will be identified. This sequence will be subjected to a mouse-human homology search and it is likely that a corresponding human gene will be identified since distal murine chr17 shares a high degree of sequence affinity with human chr 2p21.1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC /ENVIRONMENTAL INFLUENCES ON SLE NEPHRITIS Principal Investigator & Institution: Gilkeson, Gary S.; Professor; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies and immune complex mediated glomerulonephritis. African- Americans have a three-fold increased incidence of SLE, more frequently develop nephritis, more frequently progress to renal failure and have increased mortality compared to whites. The worse prognosis in African-Americans may represent a generalized predisposition towards renal failure following any renal injury rather than being lupus specific. Environmental exposures such as smoking and exposure to occupational or environmental agents (i.e., lead, mercury, silica) may affect the development and progression of lupus nephritis. Our central hypothesis is that there are specific genetic factors that interact with environmental exposures leading to progressive renal disease in African-Americans with lupus. The Carolina Lupus Study includes 265 SLE patients who were diagnosed between January 1, 1995 and July 31, 1999. This cohort of patients provides an opportunity to examine renal disease and its progression in African- American SLE patients matched with appropriate population based controls. The Gullah population lives on the sea islands of South Carolina. They are unique in their genetic homogeneity with minimal Caucasian admixture (<5%). A large ongoing study of diabetes (Sea Island Project) in this population has established a working framework onto which we propose to piggyback studies of SLE. Using these unique cohorts of patients and controls, we propose the following specific aims to address our hypothesis: 1) Determine the development and progression of renal disease in CLU patients in relation to specific genetic factors. We will assess if genes linked with renal disease in hypertension and diabetes in African-Americans are associated with

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development and/or progression of renal disease in lupus. 2) Determine the risk of development and progression of lupus nephritis in CLU patients in relation to comorbid conditions (hypertension, diabetes), measures of socioeconomic status and/or modifiable environmental factors that have been associated with other forms of renal disease. 3) Perform pilot studies in the unique genetically homogenous Sea Island African-American Gullah population to assess the presence of lupus multiplex families, the prevalence of the genetic polymorphisms being assayed in Aim 1 and determine the prevalence of ANA positivity compared to control African- American cohorts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC STUDIES - RENAL FAILURE IN HIV-1 TRANSGENIC MICE Principal Investigator & Institution: Gharavi, Ali G.; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The aim of this project is to map and identify QTLs relevant to the development of renal failure in a cross between HIV-1 transgenic (Tg26) and M. castaneus (CAST/Ei) strains. To achieve this goal, we have performed genomewide analysis of linkage in 192 backcross animals and found two loci with significant evidence of linkage on chromosome 8 (Iod 5.4) and chromosome 3 (Iod 3.5). Tow other loci on chromosomes 13 and 16 showed suggestive evidence of linkage (Iods 2.0). The 40 cM linkage interval on chromosome 8 comprises the transgene integration site, suggesting that the transgene or flanking loci influence the expression of the trait. The aims of this project are: 1. Develop congenic mouse strains by marker assisted breeding in order to "capture" the renal disease loci detected by linkage on chromosomes 8 and 3 and loci with suggestive Iod scores. After phenotypic characterization, we will proceed with meiotic mapping of the QTL in congenic strains, followed by identification of the gene(s) responsible for the development of renal failure by candidate gene analysis and positional cloning. 2. Characterization of the linked interval chromosome 8 interval that comprises the transgene integration site. Our preliminary data indicate that the transgene has integrated in the genomic locus of a novel gene, resulting in a complex rearrangement including gene duplication. We will characterize the transgene integration site and ensuing genomic re-arrangement by comparing RNA and protein expression of the novel gene and determine its tissue and cellular localization in wildtype, heterozygous and homozygous transgenic mice. These studies will also be conducted in chromosome 8 congenic mice trapping loci flanking the transgene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENOTYPE AND PHENOTYPE OF FAMILIAL NEPHROPATHY WITH GOUT Principal Investigator & Institution: Hart, Thomas C.; Associate Professor; Oral Medicine and Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Familial Nephropathy with Gout (FGN) is a rare kidney disorder characterized by reduced fractional excretion of uric acid, precocious and tophaceous gout, and development of chronic renal failure leading to end-stage renal disease. FGN is transmitted as an autosomal dominant trait, clinical fmdings are variable, response to treatment not predictable and the disease pathophysiology is

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poorly understood. The goals of this proposal are to identify the gene(s) responsible for FGN and to characterize the clinical manifestations of this condition. We have identified two large families with FGN providing unique opportunities to characterize clinical manifestations and progression of FGN and to identify the gene responsible. Our preliminary studies sublocalize an FGN gene to a 2.0 cM region of chromosome l6p in one family. Linkage data from a second, smaller family is consistent with a broader candidate interval. Additional studies will determine if the same gene is responsible for FGN in both families. The genetic interval we have mapped FGN to is not well characterized. Genetic and physical maps of the region are incomplete and there are no obvious candidate genes for FGN. We propose an integrated clinical and laboratory approach to identify the gene(s) responsible for FGN. We will longitudinally follow affected family members to better characterize clinical manifestations of FGN (Specific Aim#1). To identify the FGN gene (Specific Aim #2) we propose a hierarchical strategy to 1). Clarify and integrate genetic and physical maps of the candidate interval(s), 2). Continue linkage studies to narrow the candidate interval(s), and 3). Systematically evaluate genes within the interval to identify the gene mutation(s) responsible for FGN in these families. Identification of the specific gene mutation will provide an important discovery that will (a) elucidate important aspects of uric acid tubular transport, (b) provide an understanding of interstitial kidney disease and chronic renal failure, and (c) help to better define relationships between hyperuricemia, uric acid excretion, and the development of renal failure. Completion of these studies will permit presymptomatic diagnosis for individuals with FGN and enhance our ability to evaluate current treatment strategies as well as to develop new, more effective intervention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLYCOLIPIDS AND HEMOLYTIC UREMIC SYNDROME Principal Investigator & Institution: Haslam, David B.; Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from applicant's abstract): Hemolytic uremic syndrome (HUS) is characterized by verotoxin-mediated damage to endothelial cells that results in hemolytic anemia, throbocytopenia, and multisystemic complications including renal failure. In almost all cases, verotoxins (shiga-like toxins) released by enterohemorrhagic E. coli bind to glycolipids on the endothelial cells, are then routed to the endoplasmic reticulum, and thereby inactivate the 28S ribosomes and halt protein synthesis. Although glycolipid receptors are required for VT susceptibility, the degree of susceptibility does not correlate directly with the quantity of receptor. The clinical correlative of these observations is that children and adults differ in their susceptibility to HUS despite expressing similar quantities of VT-receptor and glycolipids in renal cells. The principal investigator therefore hypothesizes that differences in docking to verotoxin receptors or distinct pathways controlling intracellular trafficking of VT and its glycolipid receptors underlie these differences. In preliminary studies VT-susceptible Vero cells were transfected with the cDNA encoding Forssman synthetase (FS). FStransfected cells were highly resistant to VT, yet still demonstrated toxin binding. Ligand blotting demonstrated the presence of two glycolipid receptors (R1 and R2) whereas only R2, a novel receptor not previously identified, was present in FStransfected cells. In Specific Aim #1, the principal investigator will identify glycolipid receptor R2, purify this receptor from VT-resistant cell extracts, confirm its identity by mass spectroscopy, and add purified R2 glycolipid exogenously to other cell types with

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a priori resistance to verotoxin. Tandem experiments with receptor R1 will serve as a control. In Specific Aim #2, the principal investigator will analyze internalization and intracellular trafficking of verotoxin and cholera toxin receptor glycolipids in FStransfected cells and wild-type cells. Immunogold electron microscopy will be used to track the intracellular fate of labeled verotoxin in FS-transfected and WT-cells. Intracellular trafficking of cholera toxin, which binds an altogether different glycolipid (GM1) will be examined in this same system. An inducible promoter will be used to titrate expression of FS to understand whether a minimal amount of the enzyme is required for VT-resistance. In Specific Aim #3, the principal investigator will use his newly developed transgenic mouse model for overexpression of FS to characterize mRNA expression of this enzyme and alterations in glycolipid expression in various tissues. A murine model for HUS, which fails to mimic precisely the effects of VT because mice express a spectrum of glycolipids different from that in humans, will be adapted using FS transgenic mice and littermate controls to determine whether altered glycolipid expression results in VT resistance in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GPHRP KNOCKOUT MOUSE AS A MODEL OF HYPEROXALURIA Principal Investigator & Institution: Cramer, Scott D.; Cancer Biology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-DEC-2003 Summary: (provided by applicant): The long-term goal of this proposal is to develop a mouse model for Primary Hyperoxaluria Type II (PH2). PH2 is a monogenic disease that results from a genetic defect in pathways that lead to oxalate formation. Patients with this disease excrete excessive amounts of oxalate in their urine. Overproduction of oxalate can lead to calcium oxalate stone disease, nephrocalcinosis, end-stage renal failure, and systemic oxalosis. There are currently no effective therapeutic treatments for PH2. We have recently identified the molecular basis for PH2 in humans. Our data demonstrate that patients with PH2 have inactivating mutations in both alleles of the gene encoding glyoxylate reductase/hydroxypyruvate reductase (GRHPR). This is consistent with considerable biochemical evidence that suggests that the disease is a result of the lack of the GRHPR enzyme. Our data are also consistent with the hypothesis that PH2 is a monogenic disease with an autosomal recessive pattern of inheritance. Prior to our work it was thought that the source of oxalate in PH2 patients is primarily the liver and this has spurred suggestions that liver transplantation may be an effective therapeutic strategy. Our studies have demonstrated that the GRHPR gene is expressed in a wide variety of tissues and suggest that the source of oxalate in PH2 patients may not be restricted to the liver. The hypothesis of this proposal is that deletion of the GRHPR gene in mice will lead to hyperoxaluria. To test this hypothesis we will create a strain of mice containing a deletion in the GRHPR gene. In Specific Aim 1 we will generate ES cells with a targeted disruption of the mGRHPR gene. In Specific Aim 2 we will evaluate the phenotype of the GRHPR -/- mice. In Specific Aim 3 we will determine the tissue distribution of GRHPR expression and the tissue oxalate content in GRHPR -/- mice. A GRHPR knockout mouse that exhibits hyperoxaluria will be useful for the future development of novel therapeutic strategies for PH2 and for elucidating the tissue source(s) of oxalate in PH2 patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV ASSOCIATED NEPHROPATHY IN DRUG ADDICTS Principal Investigator & Institution: Singhal, Pravin C.; Professor; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Applicant's Abstract) The goal of the present proposal is to determine the role of HIV and illicit drugs such as opiates and cocaine in the development of renal injury which manifests itself as focal glomerulosclerosis (FGS) and tubulointerstitial lesions (TIL). We hypothesize that HIV-I in combination with the drugs interacts with monocytes and tubular cells (TC) and mesangial cells (MC) to induce TIL and expansion of the mesangium (precursor of FGS). Tubulo-interstitial lesions, a unique feature of HIV-associated renal injury, set the pace of the progression of renal failure. To examine the role of HIV-I and drugs in both glomerular and interstitial lesions we plan to 1) study the effect of HIV and drugs on the migration of macrophages (Mphi) into the interstitium and mesangium 2) determine the effect of HIV-l/drugs and Mphi interaction products on MC proliferation and matrix accumulation, 3) examine the effect of HIV-1 and drugs on the migrated Mphi and proliferated MC, and 4) study the effect of HIV-l/drugs and tubular cell interaction products on kidney fibroblast (KF) proliferation/apoptosis and matrix accumulation. Transmigration of Mphi across the endothelial cell layer will be determined as well as across a gelatin coated filter. Thymidine incorporation studies will be used to evaluate MC/KF proliferation. Western blots will be used to measure the laminin, fibronectin, proteoglycan and collagen components of matrix and Northern blots to measure mRNA expression for growth/cell death related genes and matrix components. A biotin-avidin assay and zymography will be used in the measurement of gelatinolytic and stromelysin activity. To examine the effect of HIV-1 gene expression, studies for cell proliferation and matrix synthesis will be carried out on MC derived from mice transgenic for HIV-I genes. In addition, these mice will be treated with drugs and acceleration of renal cortical and medullary mRNA expression of matrix components and cytokines will be evaluated. The hypothesis for the role of HIV and drugs in the development of renal injury will be tested based on our preliminary findings of increased MC/KF proliferation, and matrix accumulation when HIV-I proteins, HIV-1 protein-Mphi/TC interaction products are added to MC/KF in culture. Moreover, our results show that HIV and MC secretory/gpl20 and TC products enhance the migration of Mphi into the interstitium and mesangium. We believe that tubulointerstitial lesions determine the accelerated course of renal failure in drug addicts with HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN HEME OXYGENASE-1 GENE REGULATION IN RENAL INJURY Principal Investigator & Institution: Agarwal, Anupam; Associate Professor; Medicine; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Induction of heme oxygenase-1 is an adaptive response to injury and plays an important cytoprotective role in acute renal failure due to ischemia-reperfusion, nephrotoxins, transplant rejection and rhabdomyolysis. Heme oxygenase catalyzes the rate-limiting step in heme degradation producing biliverdin, iron and carbon monoxide. Recent studies have demonstrated that the beneficial effects of this enzyme is a consequence of important antioxidant, anti-inflammatory and antiapoptotic properties of the catalytic products. We, and others, have demonstrated that a

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number of factors (heme, nitric oxide, lipid and hydrogen peroxides, cytokines and growth factors), implicated in the pathogenesis of acute renal injury, are responsible for induction of heme oxygenase- 1. Our studies using human renal proximal tubular cells have recently discovered a novel enhancer region in the human heme oxygenase-1 gene that in conjunction with the promoter, specifically mediates gene regulation by heme and nitric oxide, but not by other known stimuli. The experiments outlined in this proposal will test the global hypothesis that specific trans-acting proteins interact with unique regulatory elements in the human heme oxygenase-l gene and mediate increased gene expression in response to heme and nitric oxide in human proximal tubular cells. Aim I of this proposal will involve characterization of the enhancer and promoter regions by deletion analysis and electrophoretic mobility shift assays. Aim II will evaluate DNA-protein interactions at the single nucleotide resolution by in vivo footprinting. The studies outlined in Aim III will evaluate the functional significance of potential DNA-protein binding regions in the enhancer element by-PCR-based sitedirected mutagenesis. Aim IV will involve studies to identify trans-acting proteins that bind to the enhancer element, using yeast one-hybrid screening. These studies will provide a basis for the development of specific molecular approaches to manipulate and fine tune heme oxygenase-l expression and thus exploit its cytoproteetive effects in renal pathophysiologic states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOXIA-MODULATION OF EPO PDNA IN ELECTROPORATED MUSCLE Principal Investigator & Institution: De Las Alas, Maida M.; Ichor Medical Systems, Inc. 6310 Nancy Ridge Dr, Ste 107 San Diego, Ca 921213209 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2005 Summary: (provided by applicant): In vivo intramuscular delivery of plasmid DNA encoding erythropoietin (EPO) using lchor's innovative and proprietary TriGrid electroporation system has resulted in robust constitutive expression of EPO in rodents, rabbits and primates. While high EPO levels are beneficial for patients with blunted responses to EPO, such high expression is not appropriate for chronic renal failure patients who are sensitive to rapid increases in EPO. Development of a physiologically modulated EPO gene therapy with a more direct communication between a patient's anemia and the intramuscularly delivered EPO transgene would thus be of benefit for this latter patient population. The necessities of monitoring hematocrit and titrating doses of the protein would be eliminated. Toxicities could potentially be decreased. Finally, abuse by non-patients would be unlikely. Ichor has demonstrated the feasibility of utilizing anemia-related hypoxia to modulate gene expression from hypoxiaresponsive plasmids transfected into anemic mouse muscle. However, this approach must be more thoroughly investigated in a more clinically relevant animal model. Experiments will be performed using rats and will include in vivo screening of HREcontaining plasmids in anemic animals, evaluation of the effect of hypoxia induced by exercise on gene expression, and assessment of hypoxia-modulated EPO transgene expression in a disease model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ILK SIGNALING IN RENAL GROWTH AND MATRIX DEPOSITION Principal Investigator & Institution: Wu, Chuanyue; Associate Professor; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2006 Summary: (provided by applicant): Renal (e.g., glomerular mesangial) cell adhesion, growth and extracellular matrix deposition are crucially involved in the progression of end-stage renal failure. The long-term goal of this competing continuation application is to elucidate the molecular mechanism by which renal cells control these processes. The studies proposed in this competing continuation application focus on the role of integrin-linked kinase (ILK), a key component of cell-matrix contact sites, in the regulation of glomerular mesangial cell behavior. Aim 1 is to test the hypothesis that a PINCH/ILKICH-ILKBP complex provides a key connection between integrins and the actin cytoskeleton at glomerular mesangial cell-matrix contact sites and thereby regulates mesangial cell adhesion, growth and fibronectin matrix deposition. Dominant negative inhibitors that disrupt the formation of the PINCH/ILKICH-ILKBP complex will be introduced into primary mesangial cells by adenoviral infection and their effects on mesangial cell adhesion, proliferation and fibronectin matrix deposition will be determined. Aim 2 is to test the hypothesis that PINCH-RP, a newly identified PiNCHrelated protein whose expression in glomerular mesangial cells is regulated by glucose, is a naturally occurring negative regulator of the assembly and functions of the P1INCH/ILKICH-ILKBP complex in mesangial cells. A combination of molecular and cellular approaches will be used to determine the functions of P1NCH-RP in mesangial cells. Aim 3 is to molecularly characterize Mig-2, a newly identified protein that colocalizes and physically associates with the PINCH/ILKICH-ILKBP complex, and to determine whether it functions as a positive regulator facilitating the localization and functions of the ILK complex in mesangial cells. These studies will advance our knowledge on the molecular mechanisms that govern glomerular mesangial cell adhesion, growth and extracellular matrix deposition. They could potentially lead to development of novel therapeutic approaches to control end-stage renal failure that is intimately associated with abnormal renal cell adhesion, proliferation and extracellular matrix deposition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTEGRINS IN ACUTE RENAL FAILURE Principal Investigator & Institution: Goligorsky, Michael S.; Professor; Medicine; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-MAR-2004 Summary: Tubular obstruction by desquamated epithelial cells plays a critical role in the development of acute renal failure. A recent observation that viable renal tubular cells rather than cellular debris can be recovered from urine of patients with acute tubular necrosis, prompted an investigation into a possible defect in cell adhesion to the basement membrane. The hypothesis to be tested in the current research proposal is that loss of focal adhesions precipitates cell detachment from the basement membrane, while the concomitant reorientation of adhesion molecules, notably integrins, from their basal location to the apical cell surface results in adhesion of dislodged cells to the remaining epithelial layer and/or conglomeration of detached cells, both events culminating in tubular obstruction. The hypothesis will be tested by exploring three experimental aims: (1) To examine the mechanisms governing stress-induced cell detachment from the matrix, notably redistribution of integrin receptors and the role of protein kinases, cytosolic calcium, and the cytoskeleton in this process; (2) To study mechanisms of cellcell adhesion of detached cells and attachment of dislodged cells to the epithelial layer; and (3) To evaluate the model of tubular obstruction in vivo and to examine the effect of maneuvers designed to reduce cell-cell adhesion and/or cell detachment on renal

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function after induction of acute ischemic or nephrotoxic injury. Cultured renal epithelial cells of primate origin (BSC-1) will constitute the in vitro model while whole animal models of acute renal failure will be used to corroborate the in vitro findings. The major techniques used in this study include intravital immunocytochemistry, interference reflection microscopy combined with microinjection of rhodamine phalloidin, digital ratio image analysis and confocal microscopy, FACS analysis, cellmatrix attachment assay, cell- cell attachment assay, molecular biological approaches for analysis of integrin mRNA. The results obtained in this research proposal will be integrated into a unifying hypothesis that will shed new light on the pathophysiologic mechanisms inducing tubular obstruction and acute renal compromise and outline potential methods of therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERVENTION STRATEGIES OF HEMORRHAGIC COLITIS AND HUS Principal Investigator & Institution: Boedeker, Edgar C.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The broad aim of this proposal is to develop and utilize new and established animal model of enterohemorrhagic E. coli (EHEC) infection, in rabbits and dogs, to develop therapeutic regimens to prevent and treat EHEC disease. It is well recognized that shiga-toxin- (Stx)-producing strains of E. coli, acquired by ingestion of inadequately cooked meat, or other contaminated foods, cause hemorrhagic colitis, and may induce fatal hemolytic uremic syndrome (HUS). EHEC strains produce potent protein toxins named Shiga-like toxins (Stxs) because of their relatedness to Shiga toxin of Shigella dysenteriae. In addition, most EHEC share the ability to adhere intimately to intestinal epithelial cells by "attaching and effacing" (A/E)(7) mechanisms (Fig.2). Although EHEC attachment mechanisms may directly contribute to diarrheal disease, and may influence toxin delivery, the most severe intestinal and renal manifestations of EHEC infection result from toxin-mediated damage to vascular endothelium, with tissue edema, inflammatory infiltrates, cytokine production and vascular thrombi. At present, only supportive care is available to prevent the development of the severe, and frequently fatal, complications of EHEC infection. Strategies aimed at decreasing the toxin burden and preventing the interaction of Stxs with their endothelial receptors should prevent or ameliorate disease and damage in target organs (gut, CNS and kidney). Interventions developed in animal models can subsequently be applied to the prevention and management of EHEC disease. E. coli strain RDEC-HI9A infection of rabbits serves as the established animal model of EHEC disease for the initial intervention studies (Aims 1-4). RDEC-H19A, produced by the transfer of the toxin-converting phage H19A of an O26:H11 EHEC to the rabbit entero-pathogenic E. coli RDEC-1, is an attaching and effacing rabbit pathogen which produces high levels of Shiga-like toxin I (Stx-I), colonizes cecum and colon, and induces intestinal disease in rabbits with pathologic changes resembling human EHEC disease. Specific aims (1-4) of the proposal are to use animal models of EHEC infection to: 1). Test the ability of new toxin-receptor analogs, administered paretenteraly or enterically to prevent EHEC disease. 2). Further test the ability of passively administered immunoglobulin with anti-toxic activity to prevent EHEC disease. 3). Further examine whether antibiotic therapy has beneficial or harmful effects on the course of disease. 4). Further develop strategies for active immunization against EHEC using the Stx toxins of EHEC. 5). Specific aim 5 is to utilize canine specific A/E

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strains to produce new STECcapable of infecting dogs, which are susceptible to renal vascular lesions. We will transfer our labeled Stx-1 encoding phage to dog-specific A/E strains of E. coli and test their ability to produce intestinal and renal disease. The clinical studies in dogs will be performed at Kansas State University by Dr. Brad Fenwick who has described the Cutaneous and Renal Glomerular Vasculopathy (CRGV) in greyhound dogs exposed to Stx. 6). Specific Aim 6 is to extend our rabbit and dog models to be able to test similar strategies against EBEC strains expressing Stx-2. We will label and transfer toxin converting phage encoding Stx-2 to rabbit and dog specific A/E strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISLET-KIDNEY TRANSPLANTS FOR TREATMENT OF DIABETIC ESRD Principal Investigator & Institution: Sachs, David H.; Senior Investigator; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Pancreatic islet transplantation is less efficient than whole organ pancreas transplantation in reversing the hyperglycemia of diabetes. One of the major reasons for this disparity is the loss of islets to ischemic injury during the time it takes for the islets to revascularize in the recipient. We have recently developed techniques for constructing composite "islet kidneys" (IK) by transplantation of autologous islets under the kidney capsule 2-3 months prior to transplantation of the composite organ into pancreatectomized miniature swine. Transplantation of IKs was found to restore euglycemia to pancreatectomized recipients immediately, and to maintain both renal and islet function long-term. Our preliminary data indicate further that a single living donor pancreas contains sufficient islets to support the insulin requirements of both the donor and recipient of such a prevascularized IK. The goal of this combined R21/R33 proposal is to perfect and optimize this approach in preclinical models (R21) and then to extend the procedure to the treatment of diabetic patients with end-stage renal disease. Specifically, in phase I (R21) we will: 1) Determine the optimal donor pancreatectomy requirements for clinical applicability; 2) Compare the efficacy of IK in maintaining euglycemia following tolerance induction vs. standard maintenance immunosuppression; 3) Establish an IK transplantation model in baboons and assess the ability of allogeneic IK transplantation to reverse hyperglycemia in diabetic baboons. In phase II (R33) we will: 1) Develop laparoscopic techniques for partial pancreatectomy, preparation of IK and IK removal for transplantation; and 2) Extend IK technology to the treatment of a major subset of patients with type 1 diabetes whose disease has progressed to end-stage renal failure. The research team assembled for this "bench-tobedside" approach includes: 1) basic scientists in the Transplantation Biology Research Center, who have been responsible for the preliminary data on which the application is based, 2) clinicians at the Massachusetts General Hospital involved in transplantation and diabetes research, and 3) consultants with outstanding expertise related to the techniques to be developed. We anticipate that the use of pre-vascularized islets as part of a composite islet-kidney transplant may provide a new and effective treatment modality for patients with class I diabetes and end-stage renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISOFLAVONES:ACUTE RESPONSE IN CHRONIC RENAL FAILURE Principal Investigator & Institution: Fanti, Paolo; Associate Professor; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506

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Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 31-DEC-2003 Summary: (provided by applicant): Up to 40 percent of ESRD patients suffer from a chronic inflammatory process which is not currently amenable to specific treatment and is associated with high morbidity and mortality. High circulating levels and production of pro-inflammatory cytokines are essential part of this ongoing acute-phase response and they are believed to exacerbate many of the clinical manifestations of ESRD, including renal osteodystrophy. Like in all other inflammatory processes that have undergone more extensive investigation, the nuclear factor, Nuclear Factor Kappa-B (NFKB) promises to be a critical cellular intermediate of this acute-phase response and to be both mediator and target of inflammatory cytokine effects. In the current search for agents that may be able to negate the ongoing acute-phase response of ESRD, the soy isoflavones genistein and daidzein have emerged as potentially useful. These isoflavones are present in many soyfoods, are available as over-the-counter nutritional supplements and have received growing attention due to their biological properties and potential as therapeutic agents. Inhibitory effects of the isoflavones on tyrosine kinase and NFKB activity, on inflammatory cytokine production and on oxidative stress have been demonstrated by this group and by many other investigators and they may be highly relevant to the renal failure population. Additionally, we have found recently that intake of soy food by ESRD patients results in very high blood levels of isoflavones and it is well tolerated. It is our working hypothesis that in chronic renal failure a variety of endogenous and exogenous factors trigger acute-phase response with activation of NFKB and production of pro-inflammatory cytokines, and that intervention with soy isoflavones inhibits NFKB activation and cytokines production, thus blocking the ongoing acute-phase response and affecting positively clinically relevant parameters of disease activity in ESRD. Specific objective of this proposal is to conduct a randomized, double-blinded dietary intervention trial in hemodialysis patients to determine whether: 1. Dietary intake of the soy isoflavones by ESRD patients with clinical signs of ongoing acute-phase response decreases the production of the proinflammatory cytokines TNF-alpha, IL-1 and IL-6 in peripheral blood, thus changing the balance between these cytokines and their antagonists sTNF RI, sTNF RII, and IL1ra. 2. Suppression of inflammatory cytokine production by soy isoflavones is associated with improvement of clinically relevant parameters of disease activity, including improvement of blood markers of acute-phase response, and decreased blood levels of markers of metabolic bone disease. 3. Intake of soy isoflavones suppresses NF-KB activity in peripheral blood monocytic cells of ESRD patients, in a manner consistent with change of cytokine levels and of clinical parameters of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF COMPENSATORY TISSUE REPAIR IN RENAL INJURY Principal Investigator & Institution: Mehendale, Harihara M.; Professor of Pharmacology & Toxicology; Toxicology; University of Louisiana at Monroe 700 University Ave Monroe, La 71209 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Renal tissue can respond to loss of tissue by toxic tissue injury by stimulating renal tissue repair. Although the importance of the nephrogenic repair response is generally accepted, biochemical characterization of this process with regard to dose-response relationships, temporal effects, molecular regulation, and effects of modulation of the repair on recovery from renal injury and survival have not been investigated. In spite of the enormous renal reserve capacity,

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toxic renal failure and death can occur due to renal insufficiency. Clinicians would welcome life saving therapies that may help them in restoring renal function by replacing the lost tissue with functional tissue. This proposal is to investigate the mechanism of renal tissue repair using a well-established murine model of nephrotoxicity induced by S-(trans 1,2-dichlorovinyl) L-cysteine (DCVC). Preliminary studies indicate that renal tissue repair is dose-dependent, increases up to a threshold, and is inhibited beyond this threshold dose causing progression of renal injury leading to renal failure and animal death. Ablation of cell division response by administration of colchicine, well after the initiation of renal injury from an ordinarily non-lethal dose of DCVC, leads to progression of injury and animal death indicating the pivotal importance of cell division in tissue repair and recovery from limited initial injury. Furthermore, administration of a low dose of DCVC (15 mg/kg) 72 h before giving a normally lethal dose of DCVC resulted in complete protection from mortality (autoprotection), suggesting that preplaced tissue repair can avert renal failure and death. In these experiments, the possibility of protection by induction of metallothionein and priming dose will be fully tested. Objective of this proposal is to test the hypothesis that timely and adequate stimulation of cell division and tissue repair determines the toxic outcome of renal injury. The specific aims are to: a) investigate the mechanism of autoprotection b) investigate if pretreatment by a low dose of mercuric chloride can protect mice (heteroprotection) from a lethal dose of DCVC; c) investigate if depletion of ATP underlies the reason for loss of cell division after a high dose and if restored ATP is the reason for autoprotection; and d) investigate molecular signaling mechanisms following a low dose, high dose, and also in the autoprotection group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF PHAGOCYTE MEDIATED ISCHEMIC RENAL INJURY Principal Investigator & Institution: Simon, Atkinson; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Taken directly from the application) Ischemia/reperfusion injury (IRI) is a major contributor to the organ damage that results in acute renal failure, one of the major causes of morbidity and mortality in hospitalized patients in the United States. IRI results in part from an inflammatory response in tissue following a period of ischemia (anoxia resulting from decreased vascular perfusion of the organ). Many factors are involved in ischemia/reperfusion injury, but considerable data points to an important role for phagocytes, and particularly neutrophils, as agents of injury in the kidney as well as other organs. The Rac2 GTPase is an important transducer of signals from cell surface receptors in neutrophils, and mice deficient in Rac2 exhibit numerous defects in neutrophil functions, including chemotaxis, adhesion and production of reactive oxygen species. We therefore propose that Rac2 deficient mice, as a consequence of defective phagocyte function, will be protected against ischemia/reperfusion injury. We propose to test this hypothesis using an experimental model of ischemia/reperfusion injury in the mouse, and to test the relative contribution of reactive oxygen species to injury using mice that lack NADPH-dependent phagocyte oxidase activity. We will exploit recent advances in gene therapy and imaging technologies to image neutrophil dynamics in live animals whose myeloid cells have been labeled with green fluorescent protein. We will use this system to investigate the effect of ischemia/reperfusion on leukocyte trafficking and apply this method to understanding alterations in neutrophil dynamics that result in attenuated ischemia/reperfusion injury in several knockout mouse

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models. These studies will provide a better understanding of the clinically important phenomenon of ischemia/reperfusion injury, and provide new methods for testing potential therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF RENAL CELL REPAIR FOLLOWING TOXICANT INJURY Principal Investigator & Institution: Schnellmann, Rick G.; Professor; Pharmaceutical Sciences; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 31-DEC-2003 Summary: The long term goal of this research is to understand how the kidney recovers from a xenobiotic insult though cell repair and regeneration. Numerous xenobiotics such as halocarbons and oxidants produce nephrotoxicity through renal proximal tubule cellular (RPTC) injury and death. The kidney can recover from renal failure through repair and regeneration of the non-injured and sublethally-injured RPTC; though the mechanisms of repair and regeneration are poorly understood. Recently, in vitro models of cell repair and regeneration using primary cultures of rabbit RPTC have been developed, and differences observed in the ability of injured RPTC to repair cellular functions and regenerate following exposure to the nephrotoxic halocarbon dichlorovinyl-L- cysteine (DCVC) and the oxidant t-butylhydroperoxide (TBHP). Extracellular matrix (ECM)-integrin interactions play a critical role in cell attachment and in triggering/transducing signals for cell proliferation and functions. Collagens are important ECM proteins and preliminary studies demonstrate that TBHP alters collagen Type IV mRNA expression in RPTC. The central hypothesis of this proposal is that repair of physiological functions and regeneration of RPTC following sublethal injury is dependent on the re-establishment of collagen production and collagen binding integrin levels and localization on the plasma membrane. Specific Aim I will determine the role of collagens I and IV in the promotion of RPTC physiological functions. Specific AIM II will determine the role of collagens and collagen binding integrins in the promotion of proliferation and repair of membrane polarity and physiological functions in RPTC following TBHP exposure. Specific AIM III will determine the role of collagens and collagen binding integrins in the lack of RPTC repair and regeneration following DCVC exposure. Completion of these aims will result in a better understanding of the mechanisms involved in renal cell regeneration and the repair of physiological functions following toxicant exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM OF RENAL TUBULAR CELL INJURY Principal Investigator & Institution: Schwartz, John H.; Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 31-MAY-2006 Summary: (provided by applicant): Goals: The overall goals of this application are to examine the role of a the 13-catenin-Lef signaling pathway in contributing to the alterations in gene expression associated with acute renal injury and to elucidate the role of this pathway in modulating events associated with recovery of renal function. Specific aims Each specific aims will test one of three interrelated hypotheses: Specific aim 1: To test the hypothesis that ATP depletion-repletion activates the Beta-catenin Lef pathway in cultured proximal tubular cells. Specific aim 2: To examine our hypothesis that ATP depletion-repletion results in beta-catenin-Lef mediated activation of gene

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expression. Specific aim 3: To test our hypothesis that the Beta-catenin-lef-1 pathway alone or in association with NF-kappB inhibits apoptosis induced by ATP depletionrepletion. Long-term goals: To elucidate the mechanisms involved in the process of recovery and repair from acute renal failure (ARF). Significance: Elucidation of the mechanisms involved in recovery and repair may lead to insight that facilitate the development of therapeutic interventions that promote recovery from ARF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF GLOMERULAR AND TUBULAR INJURY Principal Investigator & Institution: Wiggins, Roger C.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 31-JUL-2003 Summary: The major causes of chronic renal failure in the United States include conditions affecting the glomerulus (e.g. diabetes, FSGS, hypertension, and inflammatory glomerular disease), while those causing acute renal failure involve the renal tubule through toxic and ischemic mechanisms. Both types of renal failure are associated with high mortality and cost to the Nation. The human genome project offers enormous opportunities to understand and develop new strategies for manipulating signaling pathways and structural protein complexes that will have potential therapeutic and diagnostic utility in kidney diseases. To take advantage of these opportunities this Renal Center will have a Molecular/Morphology Core and four individual research projects. The individual projects are derived in part from prior work previously supported by the Renal Center, and will focus on newly discovered and cloned molecules which regulate glomerular structure and function (Wiggins, Wang and Margolis/Kershaw), on protein:protein: lipid interactions as they become uncontrolled and uncoordinated in the hypoxic tubule (Weinberg/Shayman), and on signaling systems involved in tubulogenesis that may be important in tubular regeneration following injury (Dressler/Dixon). A major role of the Molecular/Morphology core will be the production of high quality libraries of various types (e.g. RNA, cDNA, yeast two hybrid, full length cDNA for mammalian expression) for the dissection of protein interactions of importance in the glomerulus, tubule and developing kidney. In order to create this Core we have had to identify additional support ($400,000 over 5 years) from a private donor and the Institution. Our goal is that this Molecular/Morphology Core will be a resource that will serve both the Center projects and other investigators in our Institution as well as the renal community at large through rapid dissemination of the libraries that are developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF ISCHEMIC INJURY AND REPAIR Principal Investigator & Institution: Bonventre, Joseph V.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-SEP-1984; Project End 31-DEC-2002 Summary: (provided by applicant): The overall goal of the proposed studies remains to understand the mechanisms of ischemic kidney cell injury and repair with a long range goal to establish therapies that will be useful to prevent and treat acute renal failure (ARF) in man. Over the last support period we have developed and tested the hypothesis that ischemic ARF is a disease in which leukocyte-endothelial interactions, particularly in the outer medulla of the kidney, lead to congestion of the small vessels

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and impaired oxygen delivery with resultant tubule cell injury. The damaged tubule and activated endothelium contributes to additional vascular compromise by producing cytokines and chemokines which up regulate adhesion receptors and attract leukocytes. We have recently established three mouse models in which the kidney is protected against ischemic injury. These models will be exploited to evaluate the hypothesis and identify proteins that are candidates as important contributors to injury or endogenous processes of protection. In Specific Aim 1 we will use models of protection against ischemic injury to define the importance of outer medullary leukocyte and endothelial activation and interactions for the pathophysiology of ischemic acute renal failure. The state of differentiation and stress response of the S3 segment will be evaluated to put into context the potential importance of alterations in leukocyte-endothelial interactions relative to change in susceptibility to injury of the proximal tubule epithelial cell. Adhesion molecule and chemokine involvement will be studied as will the potential role of Kidney Injury Molecule-1 (KIM-I) in leukocyte-epithelial interactions. In Specific Aim 2 we will evaluate the role of nmb on leukocyte function and identify additional candidate genes implicated in inflammation that may be important for ischemic injury or inducible protective processes in the outer medulla of the kidney. We will determine the effect of nmb and three of its potential functional domains (the polycystic kidney [PKD] domain, and the YXXphi and di-leucine domains in the cytosolic tail) on binding of leukocytes to endothelial cells and on phagocytosis. Gene expression analyses will be performed by transcript profiling coupled to a gene database query. We will identify those genes that show coordinate up or down regulation under three conditions that we have identified to result in protection of the kidney against ischemic injury. Immunocytochemistry, in situ hybridization, laser capture microdissection and TaqMan real time RT-PCR will be used to identify that subgroup of genes whose expression pattern is differentially regulated in the postischemic outer medulla when comparing protected vs non-protected kidneys. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF RENAL TUBULAR EPITHELIAL CELL INJURY Principal Investigator & Institution: Shah, Sudhir V.; Professor & Director; Internal Medicine; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 21-AUG-2001; Project End 31-JUL-2006 Summary: OVERALL (Provided by the applicant) The overall mortality following acute renal failure has remained at approximately 50%. It is unlikely that this high mortality and associated cost will be reduced until we have a better understanding of the cellular and molecular mechanisms of cell injury and recovery. This program project grant application represents a multidisciplinary collaborative effort among basic scientists and clinician scientists around a central theme of elucidating the cellular and molecular basis of rental tubular epithelial cell injury, including concepts that have been learned from the study of apoptosis. Participating in the projects are members of six departments (Medicine, Pathology, Microbiology & Immunology, Geriatrics, Biochemistry and Physiology) and include several cell biologists with expertise with in vitro and in vivo models of acute renal failure (Shah, Portilla, Walker, Safirstein), investigators with expertise in molecular biology (Crew, Portilla, Haun, Price), clinician scientist who is a renal pathologist (Walker), and biochemists with particular expertise in protein purification (Kaushal, Basnakian). Additional strengths include: 1. Some of the original observations of the relevance of the concepts learned from the study of apoptosis to renal tubular injury were reported by participants in this application. 2. The program director, project leaders as well as other co-investigators have a history of professional

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association and publishing collaborative studies. The laboratories and offices of all project leaders are located in close proximity to each other allowing ready access and interaction between the participants. 3. Several of the investigators participating in the program project as well as other investigators at the institution in the Departments of Pharmacology, Physiology and the Division of Nephrology have ongoing projects that are directly related to the central theme of this grant application which further strengthens the environment to pursue the goals of the application. The program has attained a critical mass of investigators to address the pathogenesis of acute renal failure in a multifaceted, synergistic fashion thus matching the overall stated objectives of the program project guidelines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS PROGRESSION IN RENAL INSUFFICIENCY Principal Investigator & Institution: Meyer, Timothy W.; Professor of Medicine; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAY-2007 Summary: Nephrologists possess few treatments to prevent chronic glomerular disease from progressing to renal failure. The limited efficacy of these treatments prompts continuing efforts to identify the mechanisms responsible for disease progression. In chronic glomerular disease, the role of progression is strongly correlated with the amount of proteinuria. Recent studies have suggested that proteinuria causes tubular and then interstitial injury. The goal of the proposed studies is to better understand the mechanisms by which increasing glomerular protein filtration effects the tubule. Understanding of these mechanisms should ultimately facilitate design of therapies to slow renal disease progression. The first aim is to assess the effect of increased protein filtration on proximal tubule endocytic function. Filtered proteins are taken up into tubule cells by endocytosis. Endocytic function, however, has not been studied in proteinuric animals. The proposed studies will employ morphometric techniques to determine whether the tubule responds to increased glomerular protein filtration by increasing the rate of endocytic membrane cycling. Additional studies will examine the effect of increased protein filtration on key molecular components of the endocytic apparatus. The second aim is to examine whether tubular injury can be limited by blocking endocytosis of filtered proteins. At present, pharmacologic therapies to block endocytosis are not available. Studies to test the contribution of endocytosis in tubular injury will therefore be carried out in mice. The development of renal disease will be assessed in recently developed mouse strains in which tubular protein endocytosis has been reduced by gene knockouts. The third aim is to determine whether interstitial inflammation exacerbates tubular injury initiated by increased protein filtration. Tubular injury in proteinuric renal disease is invariably accompanied by interstitial infiltration of T cells and macrophages. The proposed studies will determine whether blocking chemokine signals responsible for cellular infiltration reduces the extent of tubular injury and interstitial fibrosis. These studies, like those of endocytosis, will employ knockout mice to assess the importance of potential mediators of injury which are not yet subject to pharmacologic manipulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDICAL MAINTENANCE OF HEMODIALYSIS VASCULAR ACCESS Principal Investigator & Institution: Vazquez, Miguel A.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105

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Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: End-stage renal disease (ESRD) is a devastating illness, and each year in the United States more than 80,000 new patients need initiation of therapy for ESRD. The majority of these patients will receive life-sustaining treatments in the form of hemodialysis. Unfortunately, the quality and duration of the lives of patients on hemodialysis are severely restricted by vascular access. Recent observations suggest that nearly 25% of hospitalizations in the ESRD population are related to vascular access, and problems that emanate from vascular access cost nearly $1 billion annually. Vascular access failure is arguably the most important reversible cause of morbidity in ESRD. This application is in response to RFA DK-00-012 and describes our competence to serve as a clinical center in the Hemodialysis Vascular Access Consortium. We have a strong track record in recruiting for and participating in similar multicenter trials in Nephrology, since we currently serve as large clinical sites for the African American Study of Kidney Disease and Hypertension (AASK) and the Morbidity and Mortality and in Hemodialysis (HEMO) trials. We propose a prevention trial with the cell cycle inhibitor Sirolimus (Rapamycin) in PTFE grafts. We will recruit from our pool of more than 2000 hemodialysis patients, and we will work with the Data Coordinating Center and the other sites to design and conduct a series of multicenter, randomized, placebocontrolled clinical trials of therapies to reduce the complication rate of AV grafts and fistulas in hemodialysis patients over a 5-year period. We anticipate that this consortium will be able to develop new approaches to managing hemodialysis vascular access, and that these new treatments can decrease the costs and complications of hemodialysis care of the US ESRD population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PROGRESSION

ASPECTS

OF

ALPORT

RENAL

DISEASE

Principal Investigator & Institution: Cosgrove, Dominic E.; Staff Scientist Iii & Associate Professo; Father Flanagan's Boys' Home Boys Town, Ne 68010 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAR-2003 Summary: Alport syndrome results from mutations in either the type IV collagen COL4A3, COL4A4, or COL4A5 genes. Pathology includes a juvenile onset progressive glomerulonephritis with glomerular basement membrane (GBM) rarefication and expansions of the mesangial matrix, culminating in death due to renal failure. A geneknockout mouse model for Alport syndrome was produced in this laboratory, the renal pathology of which is remarkably similar to that observed in humans. Deposition of specific extracellular matrix proteins in the GBM follows course with basement membrane rarefication. This must be due to changes in their synthesis and/or turnover. The aims of this proposal focus on clarifying the role of synthesis and degradation of basement membrane collagens and associated proteins in Aport GBM disease progression. The possible role of integrin receptors, transforming growth factor beta 1 (TGF-beta1), and metalloproteinases (and their inhibitors) will be explored. Quantitative analysis (employing material from isolated glomeruli) will be used to determine relative levels of specific mRNAs (by norther blot) and their corresponding proteins (by western blot). In situ hybridization studies will determine which glomerular cell types synthesize these proteins. Observations with potential mechanistic significance will be tested using human renal biopsy tissues from normal and Alport patients. Whether TGF-beta1 or proteinuria is linked to induction of genes encoding extracellular matrix molecules will be probed using a combination approach of TGF-beta type I and II receptor inhibitor (FK506) molecules will be probed using a combination approach of

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TGF-beta1. A double knockout of the COL4A3 and integrin alpha1 chain has been produced, and shows a marked reduction in the rate of Alport renal disease progression. The molecular mechanism of this surprising effect will be explored. Identification of the molecular mechanisms underlying the imbalance in GBM homeostasis in Alport syndrome may reveal potential targets for pharmacologic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS FOR MUSCLE PROTEIN LOSS IN CACHEXIA Principal Investigator & Institution: Lecker, Stewart H.; Assistant Professor of Medicine; Cell Biology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Muscle wasting, which occurs mainly by an activation of the ubiquitinproteasome degradative pathway, is a prominent, debilitating feature of many disease states, including diabetes mellitus and renal failure. Recently, using a newly established cell-free system, we have been able to demonstrate that rates of ubiquitin (Ub) conjugation increase in atrophying muscles from septic; tumor-bearing, diabetic and uremic rats, and that a subset of Ub conjugating enzymes, the N-end rule pathway, is responsible for most of the enhanced Ub conjunction in these atrophying muscles. This is an interesting, unexpected discovery because the N-end rule pathway has been viewed as a minor ubiquitination system that was only involved in the elimination of certain abnormal polypeptides. These results raise the possibility that in cachexia, muscle proteins may be modified to become substrates for this pathway. We propose to use our newly developed cell-free system to further characterize this process. We will measure the abundance and activity of the N-end rule pathway enzymes (E1, E2/14K, and E3alpha) to identify the ones which are responsible for the enhanced proteolysis, and identify the substrates in muscle for these enzymes. In collaborative studies, we will genetically produce animals in which these enzymes are deleted to directly show their requirement in muscle atrophy. Finally, since most of the loss of muscle protein during muscle atrophy is from myofibrillar components, we will begin to study how the myofibril may serve as a source of substrates of the Ub-proteasome pathway by developing an assay for myofibril disassembly. Defining the components of the Ubproteasome pathway and myofibril disassembly which are modulated in diabetes and renal failure should not only help to illuminate the regulation of muscle protein turnover, but also may allow the development of inhibitors that could combat the morbidity of these catabolic diseases. These studies will be performed in the laboratory of Dr. Alfred Goldberg, a leader in the fields of muscle proteolysis and the Ubproteasome pathway. The applicant is a graduate of the M.D./Ph.D. program at UCLA, completing a Nephrology fellowship at the Beth Israel Deaconess Medical Center and Harvard Medical School. His long-term goal is to develop a research program centered on problems of protein folding and degradation relevant to kidney disease. This proposal offers the unique opportunity for the applicant to obtain further cell biology training, gaining experience in animal physiology, DNA technology, and biochemistry, while studying clinically relevant problems in renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOUSE MODEL OF X-LINKED ALPORT SYNDROME Principal Investigator & Institution: Segal, Yoav; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070

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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Alport syndrome is the most common genetic disorder of the renal glomerulus, affecting an estimated 1 in 5,000 individuals. Roughly 85% of cases are X-linked, resulting from mutations in the COL4A5 gene, which encodes the c (IV) chain of basement membrane type IV collagen. There are currently no effective treatments for Alport syndrome. Males with X-linked disease suffer inexorable progression to end-stage kidney disease. Although female carriers generally have a benign course, an estimated 15% develop chronic renal failure. The premise of this application is that progress towards understanding X-linked Alport syndrome, as grounds for therapy, will be advanced immeasurably by the availability of mouse models. We are generating mouse lines with a Co14a5 point mutation, producing a premature stop, and corresponding to a known human mutation. As X-linked Alport syndrome is an archetypal basement membrane disorder, producing hematuria as a primary manifestation, we plan to build on existing knowledge of the glomerular capillary wall, to investigate the likelihood of its biomechanical failure in our model. Specific Aims are: 1) To complete generation of a transgenic mouse line with a Co14a5 point mutation; 2) To characterize basic structural and functional features of the mutant phenotype; and 3) To initiate comparison of glomerular capillary homeostasis in mutant and control mice.The Principal Investigator is an accomplished molecular biologist and physiologist with primary research interests in Alport syndrome. He joins researchers at the University of Minnesota responsible for historic contributions to this field. Additional collaborators at the University of Minnesota, with expertise in the areas of glomerular physiology and mouse genetics, will contribute to proposed efforts towards strengthening the foundations for effective therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MR ANGIOGRAPHY AND RENOGRAPHY FOR RENOVASCULAR DISEASE Principal Investigator & Institution: Lee, Vivian S.; Assistant Professor; Radiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Renovascular disease (RVD) is the most common potentially reversible cause of hypertension and renal failure in the US. Anatomic studies such as x-ray angiography are invasive, use nephrotoxic contrast agents, and do not accurately predict response to revascularization. Functional studies, such as angiotensin-converting enzyme (ACE) inhibitor (captopril) radionuclide renography, can predict response to revascularization, but do not provide important anatomic information for treatment planning. The lack of an accurate diagnostic test has also precluded definitive evaluation of optimal treatment strategies for RVD. Magnetic resonance (MR) imaging offers the unique potential to combine anatomic evaluation about RAS with functional information about renal ischemia and dysfunction in a single clinical examination. Broad, long-term objectives: To reduce the morbidity and mortality associated with hypertension and renal failure due to RVD by correctly diagnosing the disease and by determining which patients are likely to benefit from revascularization therapy and which patients should be treated with medication alone. Specific Aims/Methods: (1) To validate ultra-low dose 3D Gd-DTPA MR renography combined with T1 mapping for the measurement of single kidney GFR and other tracer kinetic parameters as compared with conventional nuclear medicine renography using 99mTcDTPA. Development and testing of a newly developed automated registration and semiautomated segmentation algorithm will also be completed. (2) To evaluate

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prospectively the accuracy of MRA combined with ACE-inhibitor MR renography, performed in a single exam, for the diagnosis of RVD, using hypertension and creatinine clearance as measures of response, as well as improvements in single kidney function (see Aim 3). A multi-compartmental tracer kinetic model will also be applied to renography results to identify more sensitive predictors of response to therapy. (3) To conduct a longitudinal study using MR renography to measure response to revascularization in terms of improvements in single kidney function as compared to global kidney function or creatinine clearance. At its conclusion, our study has a high likelihood of showing that the combination of MRA and MR renography, by uniquely providing both anatomic and functional information in a single examination, will accurately diagnose RVD and provide a comprehensive tool for measuring outcomes following therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEK1 PROTEIN KINASE AND POLYCYSTIC KIDNEY DISEASE Principal Investigator & Institution: Chen, Yumay; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Polycystic kidney disease (PKD) is the most common inherited disorder leading to chronic renal failure. Human pedigrees and several mouse models have led to cloning of genes linked to PKD. Characterization of two mice strains, kat and kat2J, both of which develop progressive PKD, has identified Nek1 (Aspergillus NIMA-related kinase 1) as a candidate protein involved in PKD. The mutations found in both kat and kat2J mice result in truncated Nekl without any coiled-coil domain at its carboxyl terminus. To date, little is known about Nekl other than its mRNA expression pattern in mice. In this proposal, Nek1 and its gene product will be characterized at molecular and cellular levels, and the potential role of Nek1 in PKD pathogenesis will be explored. In aim 1, the protein encoded by Nek1 will be characterized for its cell cycle-dependent expression pattern, kinase activity, subcellular localization, and role in kidney development. For this aim, cell and organ culture systems will be used to explore the consequences of wild type and mutant Nek1 expression via tetracycline-regulated and adenoviral vectors. Kidney tissue sections and individual cells will also be examined by immunohistochemistry. A dominant negative Nek1 mutant will be identified and used to examine its effect on kidney development in an organ culture system. In aim 2, a mouse strain in which Nek1 is specifically inactivated by gene targeting will be generated. Using the IRESbeta-geo as selection cassette, the expression of Nek1 will be monitored carefully during kidney development and cystogenesis in the nek1 null mice. Nek1 null kidney cells will be cultured from the mice and used ex vivo to examine the effects of Nek1 and nek1 mutants in a null background. Finally, in aim 3, the interaction between Nek1 and VDAC1, a mitochondrial ion channel potentially involved in apoptotic pathways, will be analyzed by molecular and physiological methods. The significance of the interaction in the pathogenesis of PKD will be explored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW ANIMAL MODEL FOR EHEC PATHOGENESIS AND PREVENTION Principal Investigator & Institution: Butterton, Joan R.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114

Assistant

Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005

Professor;

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Summary: (adapted from the application) Investigation of the gastrointestinal disease and renal injury caused by enterohemorrhagic Escherichia coli (EHEC) and the development and testing of interventions to prevent disease following infection have been hampered by the lack of a convenient animal model that effectively reproduces the typical human colonic disease that progresses to HUS. The Principal Investigator proposes to develop the use of a new mouse model of EHEC infection with the long term goal of increasing the ability to study disease pathogenesis and prevention. The new animal model will be compared with prior models in the evaluation of vaccine strategies against EHEC. This will be accomplished through the following two Specific Aims: 1. Evaluation of the use of Citrobacter rodentium expressing Stx in a mouse model of Shiga toxin-producing E. Coli (STEC) infection. C. rodentium, a naturally occurring pathogen of laboratory mice which causes transmissible murine colonic hyperplasia, binds to the mouse enterocyte by a specific attachment and effacement lesion similar to that of EHEC. Strategies have been developed to lysogenize C. rodentium with antibiotic-marked Stx1- and Stx2-expressing bacteriophages as well as to express toxin components from plasmid vectors. Toxin production, phage induction, and lysogen stability will be evaluated in vitro. Mice will be challenged with toxinproducing C. rodentium and evaluated for clinical and pathologic signs of disease. This model has the potential of reproducing both the gastrointestinal and renal injury seen in EHEC infection, allows the use of adult animals and the development of normal immune responses, utilizes the power of mouse genetics to investigate genetic factors in determining gastrointestinal (GI) and systemic disease expression, and provides a significant increase in the ease of identifying and testing new interventions compared to many other animal models. 2. Expression of nontoxic Stx1 and Stx2 antigens using a balanced lethal plasmid system in Vibrio cholerae vaccine strains. Vibrio cholerae will be used as a live oral attenuated vaccine vector to deliver immunogenic antigens of EHEC to stimulate a common mucosal immune response. A balanced lethal plasmid system will be used to provide stable expression of the heterologous antigens from the vaccine strains. The germfree mouse model of V. cholerae colonization will be used to examine mucosal and systemic immune responses to the toxin components expressed by the vector strains. The new mouse challenge model will be compared to prior mouse models in evaluating protection from disease in response to immunization with V. cholerae strains expressing the EHEC antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NITRIC OXIDE IN CHRONIC RENAL DISEASE Principal Investigator & Institution: Baylis, Christine; Professor; Physiology and Pharmacology; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 31-MAR-2005 Summary: (Applicant's abstract): There is considerable indirect evidence that in established chronic renal disease (CRD) of various causes, there is net renal and possibly systemic nitric oxide (NO) deficiency which probably contributes to both the progression of the renal disease and to the secondary hypertension. One factor which may make an important contribution to reduced NO synthesis (NOS) is accumulation of the endogenous NOS inhibitor ADMA. We propose a comprehensive series of studies, in rats, which will establish the relative contributions of different aspects of the NO system during the evolution of renal failure. These studies will include an investigation into the metabolism of ADMA. Two distinct models of CRD will be used, one of which (the 5/6th reduction of renal mass) will be employed with, and without, severe systemic hypertension. We will use in vivo functional studies to investigate renal function and

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blood pressure regulation in the conscious rat as well as regulation of the glomerular and peripheral microcirculation, using anesthetized preparations. Most studies will be in the Sprague Dawley rat, but in addition, rats will be studied who are susceptible to CRD (Dahl salt sensitive rats) and resistant to CRD (Wistar-Furth rats), to determine whether baseline NOS activity is related to the CRD susceptibility. Further, metabolic cage and in vitro studies will be conducted in various mice with targeted deletions of one or more of the NOS enzymes. In rats, interventions will be used to either ameliorate (L-arginine supplementation; angiotensin inhibition) or exacerbate (low dose NOS inhibition, urea supplementation) progression of CRD, and their impact on the NOS system will be evaluated. Harvested rat plasma will be bioassayed in vitro with cultured endothelial cells to determine its impact on NOS activity, based on our clinical observations which suggest that CRD plasma may contain NOS inhibitory elements. Cell culture studies will also explore the mechanism(s) by which uremic levels of urea inhibit L-arginine transport. These studies will, in aggregate, allow us to test the hypotheses 1) That NO production decreases progressively during CRD due to a series of alterations in the NOS system including increased levels of endogenous inhibitors. 2) That once established, the etiology of the disease is irrelevant to this progressive loss of NO function 3) That the severity and rate of development of CRD is determined in part by the initial level of NOS activity, 4) That uremic levels of urea impact on NO production via reducing substrate availability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL ADENOSINE A2A AGONISTS IN RENAL TISSUE PROTECTION Principal Investigator & Institution: Olsson, Ray A.; Professor of Medicine; Adenosine Therapeutics, Llc 310 4Th St Ne, Ste 201 Charlottesville, Va 22902 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (provided by applicant): The development of new treatments for the effective reduction of renal injury associated with acute renal failure and kidney transplantation will have a great impact on health care delivery to patients with renal disease. Acute ischemic renal failure affects 5 percent of hospitalized patients and has a mortality rate approaching 50 percent. At present, dialysis is the only FDA-approved treatment for acute renal failure. lschemia-reperfusion injury at the time of kidney transplantation causes delayed graft function and shortens graft survival. The long-term goal of this project is to evaluate the ability of a proprietary A2A adenosine receptor (A2A-AR) agonist, ATL146e to reduce renal injury in humans. The current proposal aims at completing the preclinical characterization of ATL 146e, a potent and selective A2A-AR agonist that has optimum pharmacological characteristics. Aim I addresses FDA requirements for toxicology, pharmacokinetics and metabolism. Aim 2 devises more efficient synthetic methods so that scale-up can support expanded preclinical studies and guide synthesis by certified Good Manufacturing Practices to support human studies. Aim 3 develops an in vivo assay for ATL 146e-mediated anti-inflammatory activity. Aim 4 tests the efficacy of ATL 146e in reducing injury in model of acute ischemia-reperfusion associated with kidney transplantation. PROPOSED COMMERCIAL APPLICATION: The incidence of azotemia, which includes all cases of acute renal failure (volume depletion, obstruction and intrinsic causes such as ischemia and toxins), was estimated in 1997 to be 275,000 patients per year. Additionally, it is estimated that all cases of azotemia are increasing at rate of 16,000 patients/year. The goal of this research is to develop a pharmaceutical product which will address this

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unmet medical need. All of the specific aims in this project are required by the FDA and ICH for drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL NON-HEART-BEATING DONOR KIDNEY STORAGE MEDIUM Principal Investigator & Institution: Chen, Sumi C.; Principal Investigator; Chen Laboratories, Inc. 13704 Killarney Court Phoenix, Md 21131 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-OCT-2002 Summary: Donor kidney cannot meet current demand for kidney transplantation, the most effective for end stage renal failure. Non-heart-beating (NHB) donor kidneys are under-utilized because current technology does not allow NHB donor organs to withstand unavoidable extended periods of warm and cold ischemia. Chen Medium (CM), a novel physiological preservation solution, is highly effective for human donor cornea storage and preservation. CM contains beta-hydroxybutyrate, a unique nonlactate-generating high-energy metabolite that enables tissues to generate high levels of ATP while suppressing intracellular acidosis. NHB donor organs undergo unique metabolic compromise, many aspects of which could be prevented by nicotinamide. Nicotinamide, an NAD+ precursor that is safe for humans, is idea for MHB donor organ preservation because it scavenges free radicals, preserves NDA+ levels through inhibition of poly(ADP-ribose) polymerase-mediated NAD+ catabolism, and inhibits both inducible nitric oxide synthase and expression of leukocyte-attracting molecules on human endothelial cells after injury. We propose to use physiological, biochemical and histological criteria with the isolated perfused pig kidney model to demonstrate that CM with nicotinamide is superior to UW and EC solutions for NHB donor organ preservation. Our aim is to advance transplant technology to allow effective utilization of under-utilized NHD donor organs. PROPOSED COMMERCIAL APPLICATIONS: The proposed research, if successful, will have potential commercial application. That is, CM will be able to be marked as a non-heart-beating kidney preservation medium. This is an Orphan product with a market size estimated about $20 million a year in the US and about $6-10 million for the foreign markers combined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL SAPK ACTIVATING KINASE IN RENAL EPITHELIAL STRESS Principal Investigator & Institution: Holzman, Lawrence B.; Associate Professor of Medicine; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2007 Summary: (provided by applicant): Acute renal failure secondary to tubular epithelial ischemic injury is a major cause of patient morbidity. Renal tubular epithelial cell injury results in dramatic cellular phenotypic changes including alterations in morphology and induction of genetic programs thought to be critical for regulating the cell's response to injury. Depending on the type or extent of injury, proximal tubular epithelial cells either sustain sublethal injury and recover, or die and are replaced. Investigating the proximal signaling pathways that regulate these responses should provide better understanding of the complex nature of these responses to injury. Stress activating protein kinases or cJun N-terminal kinases (JNK) are rapidly activated by multiple cellular stresses including renal ischemia/reperfusion injury and are implicated in regulating processes

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as diverse as cell proliferation, apoptosis, and development. We have identified, cloned from embryonic kidney, and initially characterized the protein kinase called DLK. DLK is a MAP kinase kinase kinase of the mixed lineage kinase family (MLK) that may be activated by cellular injury and is capable of activating JNK. In the kidney, DLK is uniquely expressed in the proximal tubular epithelium. Given these observations, we hypothesize that DLK represents a proximal component of a signaling pathway that participates in modulating the response to proximal tubular epithelial injury. In part, MLK-dependent JNK signaling might affect the tubular injury response by regulating Pax2 phosphorylation and activation. Critical for renal epithelial morphogenesis, the transcription factor Pax2 is re-expressed in proximal tubular epithelium following injury and may direct post-injury tubular regeneration. New data suggests that Pax2 transcriptional activity is regulated by JNK-mediated phosphorylation potentially via an MLK-dependent JNK pathway.This proposal seeks primarily to investigate the fundamental biochemistry and regulation of DLK within its JNK signaling complex or module. By using a combination of biochemical approaches and by characterizing a newly prepared DLK null mouse, this project will begin to investigate the role of DLKdependent signaling in the kidney. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUTRITION AND METABOLISM IN DIALYSIS PATIENTS Principal Investigator & Institution: Ikizler, Talat A.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-DEC-2007 Summary: (provided by applicant):This is a K24 application for Talat Alp Ikizler, M.D. The candidate is faculty at Vanderbilt University Medical Center (VUMC), Division of Nephrology in the "Physician-Scientist" track with 80 % effort commitment to research. The candidate has focused his research efforts on the elucidation of multiple aspects of nutrition and metabolism in renal failure patients. At the time of this application, the candidate is the principal investigator of 3 federally and 2 non-federally funded grant awards and published 31 manuscripts and 6 book chapters. He is involved in mentoring of 5 past trainees and 3 current trainees. The immediate and long-term objectives of this grant application are to provide protected time for the applicant to focus on research and mentoring activities, specifically facilitate the independence of the current trainees and recruit beginning investigators interested in a rigorous approach to clinical investigation. In addition, the candidate will take a leadership position in clinical research enterprise at the Division of Nephrology. VUMC provides excellent resources for clinical research and mentoring, including the Nephrology Training Grant, Master of Science in Clinical Investigation and Master of Public Health programs (2 current and 1 future trainee enrolled in these programs), General Clinical Research Center and Clinical Nutrition Research Unit. In this proposal, we will investigate three promising approaches to improve the nutritional status of chronic hemodialysis (CHD) patients. First, we will examine the nutritional effects of chronic inflammation on protein and energy metabolism in hemodialysis patients and test the potential beneficial effects of an anti-inflammatory agent on these parameters. Second, we will examine the comparative effectiveness of two nutritional supplementation regimens on protein and energy metabolism in malnourished patients. These protocols will incorporate detailed protein and energy balance studies utilizing stable isotope infusion techniques. In a third study, we will test the hypothesis that recombinant human growth hormone interacts with nutritional supplementation to improve nutritional parameters in 150 CHD patients

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with overt signs of malnutrition using a prospective, randomized, placebo-controlled study clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND SYMPATHETIC NERVE ACTIVITY Principal Investigator & Institution: Campese, Vito M.; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 24-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Hypertension is a common manifestation of renal disease and greatly contributes to its progression as well as to cardiovascular morbidity. Clearly, hypertension is an important etiology in the pathogenesis of renal failure. In the United States, hypertension is the primary cause of end-stage renal disease in approximately 29 percent of dialysis patients. In conjunction with other diseases such as diabetes and chronic glomerulonephritides, hypertension, when uncontrolled, hastens the progression of renal disease. Cardiovascular disease is the leading cause of death in patients receiving maintenance hemodialysis and hypertension is considered the most important factor responsible for cardiovascular events in these patients. Adequate BP control may reduce the progression of renal disease and cardiovascular morbidity in these patients, but often this is difficult to achieve with currently available drugs. The old paradigm is that hypertension in renal disease is the result of activation of the reninangiotensin system and/or volume expansion. Our studies strongly support the notion that a renal injury may result in activation of renal afferent pathways that integrate with the central nervous system, and lead to stimulation of efferent SNS activity and hypertension. Locally produced angiotensin II in the brain in response to these afferent stimuli seems to be responsible for SNS activation through inhibition of nitric oxide. Our hypothesis is that angiotensin-II activation of ROS may reduce NO availability in key brain region and result in increased SNS activity in a model of neurogenic hypertension caused by renal injury developed in our laboratory. To test this hypothesis we will pursue 3 specific Aims: 1. Test the hypothesis that locally produced Ang II mediates the activation of central SNS activity caused by phenol-renal injury. To this end, we will measure Ang II concentration in the dialysate collected from the PH using the microdialysis technique, and the expression of renin mRNA in the posterior hypothalamus. 2. Test the hypothesis that radical oxygen species (ROS) activated by Angiotensin II down-regulate nitric oxide production in the brain resulting in increased SNS activity. To this end, we will measure the concentration of reactive oxygen species (ROS) in the hypothalamus or rats with the phenol-renal injury or rats infused with Ang II in the lateral ventricle. In addition, we will evaluate the effects of anti-oxidants, or scavengers of ROS, and Ang II AT1 receptor antagonists on BP, sympathetic activation and ROS concentrations in the hypothalamic region. 3. Test the hypothesis that increased ROS production may result in NO inhibition and SNS activation in other forms of experimental hypertension, such as the DOCA-sait model, and the renovascular hypertension model. If our hypothesis were to be correct, administration of inhibitors of the renin-angiotensin system particularly if combined with antioxidants should result in better control of BP in these models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSPORT

PATHOPHYSIOLOGY

OF

ARPKD:

ROLE

OF

ABERRANT

Principal Investigator & Institution: Satlin, Lisa M.; Professor; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029

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Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2003 Summary: The hereditary forms of polycystic kidney disease (PKD) include the common autosomal dominant form (ADPKD), affecting 1 in approximately 1000 of the population, and the less common autosomal recessive form (ARPKD), affecting 1 in approximately 20,000 live births. Both diseases are characterized by the formation and expansion of cysts derived from specific segments of the nephron. In ADPKD, the gradual destruction of normal renal parenchyma by cysts arising in multiple nephron segments lead to renal failure in approximately 50% of patients by the sixth decade of life. ARPKD, a disease with high infant morbidity, is characterized by the progressive dilatation of collecting ducts, the nephron segment responsible for the final renal regulation of Na, K, acid-base and water balance. Three mechanisms have been implicated in the process of cyst formation and expansion: cell proliferation, abnormal extracellular matrix and adhesion, and net transepithelial fluid. Whereas data exists to implicate the former two processes in the pathogenesis of ARPKD, little is known about the regulation of transepithelial solute and water transport in this disease. Our long term goal is to identify alterations in the expression and regulation of epithelial cell transport pathways that contribute not only to cyst expansion, but also the early onset of hypertension and polyuria in APRKD. The hypotheses we propose to examine in this 5year application are focused on (I) characterizing the molecular and functional expression of ion channels, transporters, and receptors, and (II, III) exploring the mechanisms by which aberrant autocrine/paracrine signaling and/or cellular responses to biomechanical forces lead to dysregulated transepithelial transport in ARPKD collecting dust cysts. To best understand the pathogenesis of human disease, we propose to perform most studies described in this application in immortalized principal cell lines derived from human ARPKD collecting duct cysts or age-matched normal human kidney (NHK). Parallel studies will also be performed in the orpk murine model of ARPKD, whose microdissected tubules can be isolated and microperfused in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATIENT ORIENTED RESEARCH IN KIDNEY DISEASE Principal Investigator & Institution: Powe, Neil R.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-MAY-1999; Project End 31-MAR-2004 Summary: (adapted from the application) Neil R. Powe, M.D., is Associate Professor of Medicine and Director of the Welch Center at the Johns Hopkins University School of Medicine. He holds a joint appointment in the Department of Epidemiology at the Johns Hopkins School of Hygiene and Public Health where he is Director of the Clinical Epidemiology Program. He is seeking this Midcareer Award in Patient-Oriented Research to concentrate his effort in clinical research in kidney disease and build the training program in kidney disease research. Dr. Powe has conducted several clinical investigations in nephrology over the past 12 years including a study of the effectiveness of recombinant human erythropoietin for treatment of anemia of ESRD (end stage renal disease), a study of the incidence, risk factors and prognosis of septicemia in ESRD patients, a study of co-morbid cardiovascular disease in ESRD patients, a study of the natural history and risk factors for ESRD among patients with diabetes mellitus, a study of the impact of dialysis care deficiencies on patient mortality and hospitalization, a study comparing physical examination with color flow Doppler for detection of vascular access failure and a randomized clinical trial and observational studies of high versus low osmolality contrast media-induced nephrotoxicity. Dr. Powe directs the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study. This is a national prospective

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cohort study comparing peritoneal dialysis and hemodialysis and a large versus small dose of dialysis. The study now has over 1034 patients enrolled making it one of the largest and most representative prospective cohorts of dialysis patients ever studied in the U.S. Data on medical history, laboratory studies, co-morbidity and severity of disease and clinical outcomes are being collected. The study has also established a specimen bank which provides exciting opportunities for studies examining both the etiology and consequences of kidney disease or its treatment. Dr. Powe has mentored a cadre of trainees and junior faculty in clinical research in kidney disease. This award will permit Dr. Powe to make even a greater contribution to patient-oriented research in nephrology, concentrating his efforts and helping him produce future clinical scientists who are rigorously prepared to becomes independent investigators in kidney disease research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC TRAINING PROGRAM IN CHRONIC KIDNEY DISEASES Principal Investigator & Institution: Hruska, Keith A.; Professor of Pediatrics; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The objective of this application is to foster the growth and development of pediatric physician scientists in nephrology. There is a paramount need for individuals knowledgeable in this clinical area of pediatrics and skilled in modern scientific methods to provide new understanding and novel approaches to the treatment of childhood renal disease and hypertension. The Pediatric Nephrology Division at Washington University has new directorship under Keith A. Hruska, an established investigator in chronic renal failure. Under Dr. Hruska's leadership, a Renal Fellowship Training Program for physician scientists has been activated. Dr. Hruska has previously led an institutional NRSA. The Division has exciting opportunities in clinical, translational and basic research related to new potential therapies for chronic kidney disease. The training program will be targeted toward the development of physician/scientists armed with the necessary skills to bring forward new therapies for chronic kidney diseases, especially in the pediatric population. The program faculty includes experienced individuals in four research areas: molecular and cellular biology, skeletal biology, clinical research, and chronic renal failure/pathophysiology. These program areas, each of which includes faculty from the Department of Pediatrics, will serve to foster collaborative interactions among faculty within the University and the Pediatric Nephrology Division with a similar interest to provide trainees with the opportunity to develop their investigative careers and attack chronic kidney disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PODOCYTE DYSFUCTION IN DIABETIC GLOMERULOPATHY Principal Investigator & Institution: Chen, Sheldon C.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: Dr. Sheldon Chen is currently conducting his research in the laboratory of Dr. Faud N. Ziyadeh at the University of Pennsylvania, which boasts a world-renowned biomedical community and provides state- of- the-art facilities, superb human resources, and outstanding technical support. By completing the proposed project, Dr.

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Chen hopes to acquire new technical expertise, improve his ability to synthesize data into a credible paradigm, hone his critical thinking skills, and afterwards pursue novel or related research that expands upon his findings. After an additional year of mentored fellowship research training, he will join the faculty of the Renal Division at the University of Pennsylvania, where he hopes to mature into a fully-independent academic physician-scientist. Diabetic kidney disease remains the number one cause of renal failure in the United States. As the defining metabolic abnormality in diabetes mellitus, high blood glucose undoubtedly plays an important role in the pathogenesis of diabetic nephropathy. Our laboratory has discovered that Transforming Growth Factorbeta (TGF-beta) mediates much of the injuries effect of hyperglycemia, and the two metabolic factors may conspire to cause even greater renal damage. The podocyte is a highly specialized epithelial cell in the glomerulus that synthesizes part of the glomerular basement membrane (GBM) and regulates the macromolecular permeability across the glomerular filtration barrier. Podocyte dysfunction secondary to the deleterious environment of the diabetic milieu may contribute to the GBM thickening and increased macromolecular permeability leading to proteinuria in diabetic glomerulopathy. Recent cell culture advances have allowed us to study the in vitro podocyte in its fully differentiated state. We propose to examine the effects of high glucose and exogenous TGF-beta on the cultured, differentiated mouse podocyte with respect to the altered expression of type IV collagen and vascular endothelial growth factor (VEGF), two proteins that are likely involved in the pathophysiology of GBM thickening and diabetic proteinuria. Northern analysis will be used to quantitate the gene expression, and immunoblotting and ELISA will be used to measure the protein production of the component alpha chains of collagen IV and the isoforms of VEGF in response to high glucose and TGF-beta treatment. Whether high glucose and TGF-beta have synergistic effects will also be investigated. The cellular mechanisms underlying the high glucose-induced expression of the TGF-beta signaling receptor (preliminary data), which may explain the hypothesized high glucose/ TGF- beta synergy, will be elucidated by the nuclear runoff technique, analysis of promoter activity by luciferase reporter assay, and electrophoretic mobility shift assay. Lastly, specific inhibitors of TGF-beta will be used to determine whether some of the high glucose effects may be mediated by the TGF-beta system in the podocyte. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYAMINE METABOLISM IN HEART AND KIDNEY ISCHEMIC INJURY Principal Investigator & Institution: Soleimani, Manoocher; Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 06-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Conditions associated with ischemia/reperfusion injury (IRI) such as myocardial infarction and acute ischemic renal failure are among the major causes of morbidity and mortality. The pathophysiology of IRI is strikingly similar in heart and kidney, with enhanced production of toxic metabolites (i.e. H202), increased apoptosis, and cell death following reperfusion, raising the possibility that identical pathway(s) may mediate cell injury and dysfunction in both organs in IRI. In an attempt to identify the factors involved in the pathophysiology of IRI, suppression subtractive hybridization on RNA from normal rat kidneys and kidneys of animals subjected to 30 min of ischemia (renal artery ligation) followed by 12 hrs of reperfusion was performed. The results identified enhanced expression of Spermidine/Spermine N1 acetyltransferase (SSAT), the rate limiting enzyme involved in the catabolism of

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polyamines, in IRI. Interestingly, thirty (30) min of ischemia (left anterior descending artery ligation) followed by 6-12 hrs of reperfusion resulted in the induction of SSAT in the injury zone in myocardium, with SSAT expression being almost undetectable in normal myocardium and increasing by >50-fold at 6 hrs of reperfusion. Enhanced SSAT expression in kidney and heart in IRI was associated with increased concentrations of putrescine, a mediator of apoptosis and a phenomenon indicative of increased activity of SSAT. Conditional overexpression of SSAT in cultured cells resulted in decreased cell growth. The studies outlined in this proposal will test the hypothesis that SSAT is a biomarker of cell injury and its increased expression reflects the extent of tissue damage associated with IRI in heart and kidney. We further hypothesize that enhanced expression of SSA T in kidney or heart leads to cell damage through depletion of polyamines, production of toxic metabolites (e.g. H202, putrescine and various aldehydes) and induction of apoptosis. To test these hypotheses, we propose to: 1. Examine the expression and regulation of SSAT and polyamine pathway in renal and heart IRI, 2. Ascertain the role of SSAT over expression on cell survival and susceptibility to injury in renal and cardiac IRI, and 3. Ascertain the mechanism of SSAT-mediated cell injury in renal and cardiac IRI. Insight into the expression and regulation of SSAT and other enzymes involved in polyamine metabolism in IRI will shed new lights into the pathophysiology of IRI in heart and kidney and may provide basis for novel diagnostic tests and therapeutic options targeted at early detection, prevention or treatment of ischemic heart attack and acute ischemic renal failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF LEFT VENTRICULAR HYPERTROPHY AND RENAL FAILURE IN PKD Principal Investigator & Institution: Krugman, Richard D.; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-DEC-2000; Project End 31-MAR-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEIN KINASE C IN THE REPAIR OF CELLULAR FUNCTIONS Principal Investigator & Institution: Nowak, Grazyna; Pharmacology and Toxicology; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Adopted from the Applicant's Abstract): The long-term goal of this research is to elucidate the mechanisms that regulate the recovery of physiological functions in renal proximal tubular cells (RPTC) following toxicant-induced injury. Kidney exposure to a variety of drugs and toxicants results in acute renal failure (ARF). RPTC are the major target for many nephrotoxicants and the recovery of the kidney following injury occurs through the regeneration of the non-injured and repair of sublethally-injured RPTC. Therapeutic strategies used to treat ARF are often unsuccessful due to the poor understanding of the mechanisms regulating RPTC regeneration and repair. The goal of this proposal is to elucidate the role of 3 major isozymes of protein kinase C (PKCx, PKCo, and PKCc) in the repair of RPTC functions following toxicant-induced injury. In our in vitro model of cell regeneration and repair (primary cultures of rabbit RPTC grown in improved culture conditions) RPTC recover their mitochondrial and transport functions following exposure to an oxidant (tertbutylhydroperoxide, TBHP) but not a halocarbon (dichlorovinyl-L-cysteine, DCVC). Inhibition of these functions in

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sublethally-injured RPTC following TBHP exposure is accompanied with the decrease in protein kinase C (PKC) activity. Activation of PKC prior to TBHP exposure accelerates recovery while inhibition of PKC prevents the return of RPTC functions. Lack of RPTC repair after DCVC exposure is accompanied by sustained inhibition of PKC activity and PKC activation prior to DCVC exposure promotes recovery of RPTC functions. Therefore, the central hypothesis of this proposal is that PKCa, PKC6, and PKCc play a pivotal role in the repair of mitochondrial and transport functions of RPTC following toxicant injury and that the recovery of these functions depends on re-establishment of PKC-mediated signaling. Specific Aim I will examine the alterations in the activity, protein levels and subcellular localization of major PKC isozymes after toxicant injury and during recovery. Specific Aim II will demonstrate that the recovery of mitochondrial and transport functions following toxicant injury is mediated through PKCa, PKCS and/or PKCe. Specific Aim III will identify pathways that are involved in regulation of recovery of RPTC functions by PKC. Completion of these aims will result in a better understanding of the role of PKC isozymes in the repair of RPTC functions and may help to identify agents that protect against ARF or accelerate recovery from ARF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMIC ANALYSIS OF DIABETIC NEPHROPATHY Principal Investigator & Institution: Klein, Jon B.; Professor; Medicine; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 03-JUL-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Diabetics now account for more than 40% of patients with end-stage renal disease (ESRD) and the number of diabetics with renal failure is expected to grow in the coming years. Diabetic nephropathy occurs following alterations in all structures of the kidney including blood vessels, interstitium, tubules and glomeruli. To better understand the cellular mechanisms of diabetic nephropathy we will perform proteomic analysis of renal tissue in two very different models of diabetes, 0VE26 transgenic mice and db/db mice, both of which display characteristics of human ESRD. The db/db model is initially insulin resistant and resembles human Type II diabetes. 0VE26 mice are severely hypoinsulinemic and thus are more similar to human Type I diabetics. The intent of this two-model analysis is to distinguish proteins critical to the process of diabetic nephropathy from proteins that are merely characteristic of insulin deficiency or insulin resistance. In an initial analysis of 0VE26 diabetic kidneys, we have identified 80 proteins in the murine renal proteome and demonstrate increased expression of three groups of proteins:1.) Serine protease inhibitors;2.) Cell cycle regulatory proteins;3.) Smooth muscle contractile elements. Increased expression of these proteins is consistent with previous studies that described increased matrix and endothelial proliferation in diabetic nephropathy. However, these preliminary data also identify potential novel mechanisms by which diabetic nephropathy progresses. This suggests the hypothesis to be tested that proteomic analysis can identify novel mechanisms of diabetic nephropathy. The Specific Aims that will address this hypothesis are to: 1. Produce proteome maps of kidneys from diabetic mice with insulin resistance and hypoinsulinemia. 2. Produce proteome maps of glomeruli from diabetic mice with insulin resistance and hypoinsulinemia. We will produce proteome maps using high-resolution two-dimensional gel electrophoresis. Extracted renal proteins from our hypoinsulinemic transgenic 0VE206 mouse model and the obese hyperinsulinemic db/db mouse model will be resolved by electrophoresis and identified by peptide mass fingerprinting. Comparison of the renal and glomerular

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proteome in hypoinsulinemic and insulin resistance diabetes to normal kidney may reveal candidates for disease mechanisms, therapeutic targets and biomarkers whose validity can be tested in further hypothesis driven research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROXIMAL TUBULE ANGIOTENSINS--HEMOLYTIC UREMIC SYNDROME Principal Investigator & Institution: Ingelfinger, Julie R.; Professor of Pediatrics; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from the application) Most studies of hemolytic uremic syndrome (HUS), a leading cause of acute renal failure in children, have focused on mechanisms of thrombotic microangiopathy and endothelial injury. However, until recently, consideration of the renal tubule as a site for primary damage by shiga-like toxin [Stx] has been largely tangential. It has now been reported that human proximal tubule cells [PTCs] are exquisitely sensitive to damage by Stx. Much work on pathogenesis has shown that Stx-related disease leads to abnormalities in coagulation factors, increased shear forces, oxidant injury, platelet activation, rbc injury, with involvement of multiple cytokines and vasoactive substances. While much attention has focused on changes in endothelin, NO, and vasodilator substances, little has been paid to the potential role of the renin-angiotensin system [RAS] in modulating the severity of HUS. In recent years, the interaction of the RAS with coagulation factors and cytokines has been recognized as important in both normal and pathophysiologic states. This application will focus on the unique role of the PTC tissue RAS, hypothesizing that local angiotensins amplify the effects of Stx in PTC, resulting in further injury. Thus, we will define the roles of the local proximal tubular RAS in HUS. We hypothesize that Stx-induced proximal tubule cell [PTC] injury initiates a pathologic series of events in which the RAS and the coagulation cascade interact as follows: PTC injury results in heightened Ang II generation. Altered glomerular and tubular shear forces lead to impairment of tubular fluid flow, accumulation of debris with rbc and leukocytes with near stasis, and even hypoxia. Angiotensins in this milieu in the presence of Stx and leukocyte and PTderived cytokines [e.g., IL-1, TNF], favor PTC expression of tissue factor [TF, present in PT], PAI-1 and other pro-fibrotic factors. Furthermore, TF in the tubule may become further upregulated in view of exposure of PTC to blood products due to glomerular injury. Interrupting these interactions may abrogate or mitigate Stx-induced damage. The specific aims of this application are: 1. To demonstrate that Stx enhances the expression of the local RAS in proximal tubule cells [PTC], as well as in glomerular endothelial and mesangial cells, which, in turn, modulates tissue factor PAI-1, and cytokine production, contributing to tubular damage in HUS. Preliminary data suggest that Stx increases angiotensinogen and angiotensin converting enzyme (ACE) generation in PTCs, which are exquisitely sensitive to Stx 2. To demonstrate that Stxinduced RAS, in turn increases local TF, PAI-1 and cytokine production, contributing to tubular damage in HUS. We hypothesize that Stx-induced PTC injury is modulated by RAS, coagulation pathway and cytokine interaction, and influences PT functions. We will examine PTC under static and flow conditions, alone and in proximity to glomerular endothelial and mesangial cells; we will concomitantly study tissues from the baboon model of Stx-induced HUS using rheologic techniques and molecular studies. 3. To demonstrate abrogation of Stx-induced injury in PTC by blocking the interaction of angiotensins, shiga toxin, and the coagulation pathway. Using the same systems, the interaction of the RAS, coagulation factors and cytokines will be blocked

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sequentially and specifically in order to define the mechanism of these interactions. It is anticipated that specific blockade may lead to strategies with clinical relevance for the possible prevention or amelioration of HUS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REAL-TIME FLUORESCENCE-ACTIVATED RENAL MONITOR Principal Investigator & Institution: Rabito, Carlos A.; Diametrx, Inc. 1 Arcadia Rd Natick, Ma 01760 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JAN-2004 Summary: (adapted from the applicant's abstract): Real-time and accurate data of the renal function are needed to develop new approaches for the prevention and treatment of acute renal failure (ARF). Current techniques have neither the accuracy nor the resolution time required. A highly innovative approach, was recently developed for the real-time and accurate measurement of glomerular filtration rate (GFR). The technique determines, minute-to-minute, the rate of disappearance from the extracellular space (ES) of a radiolabeled GFR agent as measured with an external radioactivity counting device. Although the approach showed excellent results, the use of radioactivity, limit its application. As an alternative, this project proposes the use a GFR agent labeled with a laser fluorescent dye (FGFR). The project involves the synthesis of the agent, the design and assembly of an instrument to measure the laser-induced tissue fluorescence (LITF) and the initial validation of the technique in rats. The synthesis of the agent will be performed by labeling with a laser fluorescent dye a well established GFR agent. A laser photodiode will be used in the instrument for the excitation beam. The LITF will be measured and recorded for further processing. At a constant excitation, LITF should be proportional to the tissue concentration of FGFR. This concept will be validated in rats by comparing the LITF with direct tissue concentration after extraction of the dye. This alternative method should represent a significant advance, not only for immediate detection of renal dysfunction to avert ARF, but also for the instant evaluation of the response to therapy in patients with ARF. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF SKELETAL GROWTH IN RENAL FAILURE Principal Investigator & Institution: Sanchez, Cheryl P.; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Growth retardation occurs invariably in children with chronic renal failure; secondary hyperparathyroidism and tissue resistance to the actions of IGF-1 are major contributors to impaired growth. Calcitriol and recombinant human growth hormone are widely utilized to improve liner growth in children, but large intermittent doses of calcitriol have been shown to suppress bone formation and to induce adynamic lesions of bone; moreover, substantial reductions in linear growth have been reported during intermittent calcitriol therapy in children with renal therapy. These findings suggest that calcitriol can modify chondrocyte proliferation and/or differentiation in epiphyseal growth plate cartilage and may counteract the effect of recombinant human growth hormone to increase linear growth in children with chronic renal failure; the mechanisms responsible for these changes remain unknown. Parathyroid hormone related peptide (PTHrP) and the PTH/PTHrP receptor play critical roles in regulating chondrocyte differentiation in the epiphyseal growth plate, and PTH/PTHrP receptor

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expression is down- regulated in the growth plate cartilage of rats with renal failure; there is limited information, however, about the impact of renal bone disease per se or treatment with calcitriol or growth hormone is modifiers of the expression of PTH/PTHrP or other molecular markers of endochondral bone formation in renal failure. In the current project, chondrocyte proliferation will be assessed by bromodeoxyuridine (BrdU) incorporation and apoptosis of hypertrophic chondrocytes will be measured by the TUNEL assay in rats with renal failure and either secondary hyperparathyroidism or adynamic lesions of bone; the width of the growth plate will also be measured by quantitative histology. The technique of in situ hybridization will be used to quantify the expression of mRNAs for the PTH/PTHrP receptor, type II and type X collagen, alkaline phosphatase and IGF-1 in each disorder. The separate and combined effects of calcitriol and growth hormone on selected molecular markers on endochondral bone development will be examined in rats with adynamic renal bone disease, and the effect of continuous versus intermittent calcitriol therapy on the expression of these markers will be determined. The results of these studies will determine whether alterations in the regulation of chondrocyte proliferation and differentiation contribute to impaired linear growth in experimental renal failure and whether changes in the expression of known regulators of endochondral bone formation and chondrocyte differentiation account for these disturbances in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESISTANCE TRAINING DURING MAINTENANCE DIALYSIS Principal Investigator & Institution: Sceppa, Carmen C.; Nutrition Exercise Physiology Sarcopenla (Neps) Lab; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2005 Summary: (provided by applicant): There is a rising incidence of kidney failure in the US, with poor outcomes and high cost. End-stage renal disease (ESRD) affects almost 375,000 individuals in the US at a cost of more than $14 billion per year. Despite advances in dialysis and transplantation therapies, kidney failure leads to poor outcomes, poor prognosis and high health care costs. Malnutrition and the underlying systemic inflammatory response developed during the course of chronic kidney disease, worsen during ESRD, and leads to adverse outcomes, increased morbidity and mortality. Muscle wasting, impaired functional capacity and poor quality of life are the most important factors associated with malnutrition and inflammation in renal failure. We have shown in pre-dialysis patients with moderate chronic renal insufficiency that the anabolic effects of resistance exercise training result in significant improvements in protein utilization, nutritional status and functional capacity even in the context of anorexia and prescribed low protein diets. Thus, we propose to develop, test and implement a progressive resistance exercise routine for ESRD patients during the hemodialysis session. Our hypotheses are that the addition of 30-45 min of resistance exercise training during the dialysis session will counteract the burden of renal disease and will result in: 1) A feasible and safe exercise modality for ESRD patients (6-wk feasibility phase tested in 10 patients); 2) Net anabolism as evidenced by: improved nutritional status (i.e. increased protein catabolic rate, muscle mass and muscle strength); and reduced systemic inflammatory response (i.e. reduced C-reactive protein and interleukin-6, and increased serum albumin levels) compared to a randomly assigned control group on hemodilaysis but not exercise training (6-mo efficacy phase tested in 20 patients/group); and that 3) Improved self-reported physical function (i.e. increased SF-36 physical component scale) observed with resistance training will be associated with the improvements in nutritional status and inflammatory response. The

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long-term goal is to implement resistance exercise training routines during hemodialysis to overcome the underlying malnutrition and inflammation of ESRD and to improve disease outcome and prognosis. By implementing such intervention, we hope to offer a therapeutic strategy that can be incorporated to the standard of care of ESRD patients by working in conjunction with the dialysis unit staff. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS FOR CV DISEASE IN A DIALYSIS COHORT Principal Investigator & Institution: Coresh, Josef; Associate Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from Investigator's Abstract) Atherosclerotic cardiovascular disease (ASCVD) is a leading contributor to the high morbidity and mortality among end-stage renal disease (ESRD) patients, accounting for 36 percent of ESRD deaths (total annual mortality of 23 percent). This application tests the hypothesis that higher levels of several novel risk factors (Lp(a) levels and apo(a) isoforms; homocysteine and related vitamins; Chlamydia pneumoniae and cytomegalovirus; and C-reactive protein and fibrinogen) and traditional risk factors predict higher risk of ASCVD in a prospective study of 925 incident dialysis patients recruited within three months of starting dialysis. Although these factors have been implicated in the etiology of ASCVD in ESRD patients, little prospective data exist. Cross-sectional studies are susceptible to large survival bias because of the high mortality of patients with renal disease. This cohort has already been recruited through a collaboration between Johns Hopkins and 80 Dialysis Clinics Incorporated (DCI) clinics; many of the important predictors and possible confounders have been measured. This application proposes to obtain long term followup (extending mean followup of 2.4 years by four more years) and conduct laboratory assays. The investigators will: 1) extend specimen collection, and follow-up, and institute standardized review of ASCVD events; 2) characterize baseline associations of novel and traditional factors with each other, dialysis modality and dose, nutritional status, and ASCVD prevalence in the full cohort using a cross-sectional design; 3) determine whether baseline levels of risk factors predict subsequent incidence of ASCVD events, and total mortality using a prospective cohort study design and test a priori hypothesized interactions between risk factors and the risk of ASCVD; 4) study the variability of risk factors over time using annual measurements in a random subset of 180 patients (subcohort) using a longitudinal design; and lastly, 5) use a case-cohort design, utilizing the subcohort, to test whether the most recent level before an ASCVD event, the baseline level, or the mean level of each risk factor is most predictive of ASCVD risk. Baseline data collection will include a patient health questionnaire and a standardized review of comorbidity using dialysis chart records. Serum, plasma and DNA will be stored at -80 degrees C. from patient visits at recruitment (month 0), and followup (months 1,2,3,6,12,8,24, etc.). ASCVD will be assessed by review of hospital charts, patients and care providers questionnaires, and HCFA death forms. The investigators state that this study will use state-of-the-art epidemiologic and laboratory methods to identify modifiable risk factors, answer the call of an NKF task force for prospective studies of risk factors for ASCVD in the dialysis population, and lay the essential groundwork for future preventive interventions to reduce the burden of ASCVD in persons with ESRD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLES OF KIM-1 IN RENAL INJURY AND REPAIR Principal Investigator & Institution: Han, Won K.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The applicant proposes a program of research to prepare him for a career in the academic medicine. The research will be conducted in the laboratory of Dr. Joseph Bonventre at the Massachusetts General Hospital. Dr. Bonventre is an established senior investigator with an interest in acute renal failure who has successfully trained research fellows with a variety of interests. The long-term objective of the applicant is to independently investigate mechanisms of acute renal failure and improve the therapy and outcome of patients with this disease. The proximal tubule is particularly sensitive to ischemic injury and the surviving cells in this segment undergo an active process of dedifferentiation and proliferation after ischemia ultimately resulting in the reconstitution of a well differentiated polarized morphology. However the mechanisms by which the tubular epithelial cells are restored are not fully understand. Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane protein and an epithelial cell adhesion molecule, which expresses predominantly in the injured kidney. After ischemia/reperfusion KIM-1 is coexpressed with vimentin, a marker of epithelial cell dedifferentiation. KIM-1 is also expressed in renal cell carcinoma, which state is associated with a dedifferentiated epithelial cell phenotype. The cleaved ectodomain of KIM-1 can be detected in the urine of patients with ischemic acute renal failure. In pilot experiments, we have found that tumor necrosis factor-alpha (TNFalpha) enhanced the shedding of KIM-1 and, meanwhile, inhibitors of MEK-1, secretory phospholipase A2, and cyclooxygenase diminished the TNF-alpha induced shedding of KIM-1 in 769-P cells, which express abundant level of endogenous KIM-I under normal culture condition and constitively shed into culture media. This project's broad objectives are to define the functional role of KIM-1 and specific signaling mechanisms controlling cytokine mediated-shedding of KIM-1 in renal epithelial cells. The studies proposed in this application will provide important new insights regarding understanding functional role of KIM-1 in injury and repair of the renal tubular epithelium and may lead to new therapeutic approaches in acute diseases affecting the kidney. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SHIGA TOXIN MODE OF ACTION IN BACTERIAL DISEASE Principal Investigator & Institution: Obrig, Tom G.; Research Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-APR-1990; Project End 31-DEC-2007 Summary: (provided by applicant): Shiga toxin-producing E. coil (STEC) is an emerging infectious pathogen that causes in excess of 30,000 cases of disease per year in the United States. STEC, including E. coil O157:H7, is also the leading cause of acute renal failure, hemolytic uremic syndrome (HUS), in young children. No effective preventive modality or therapeutic intervention is currently available for this disease. This project is designed to more fully describe a "window of opportunity" available for treatment and prevention of STEC-associated acute renal failure. In most cases, a three to nine day period of renal inflammation takes place between the appearance of bloody diarrhea and the onset of acute renal failure. It is believed that STEC virulence factors such as Shiga toxin (Stx2) and lipopolysaccharide (LPS) are the primary initiators of the renal disease. These factors elicit production of pro-inflammatory host cytokines and

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chemokines. This study utilizes a murine model to define the cytokines and chemokines involved and describe how these agents cause migration and accumulation of inflammatory cell types in the kidney. These cell types include neutrophils, monocytes/macrophages and platelets. Mice with mutated cytokine, chemokine, or adherence factor genes are to be employed to determine which of these factors are required in the disease process. In addition, adherence of these cell types to isolated endothelial cells under flow conditions is included to define the inflammatory action of Stx2 and LPS. Studies are also included to show how host cytokines and chemokines further sensitize endothelial cells to Stx2 by activation of intracellular signal transduction pathways. The goal of these studies is to reveal the opportunities available for effective application of therapeutic agents in STEC-associated renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING BY GAB1 IN EPITHELIAL MORPHOGENESIS Principal Investigator & Institution: Cantley, Lloyd G.; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: The ability of kidney epithelial cells to regulate their morphology is critical for developmental nephrogenesis and tubular repair following renal injury, suggesting that understanding how epithelial cell morphologic events are regulated will provide us with unique tools for enhancing recovery from acute renal failure and potentially modifying the course of chronic renal tubular diseases. This proposal focuses on a newly discovered cytosolic signaling protein, Gab 1, which has been found to associate in a regulated fashion with the receptors known to mediate morphogenesis and to directly initiate renal epithelial cell tubulogenesis in cell culture. We have found that one region of Gab1, the met-binding domain (MBD), can associate in a phosphorylation- specific manner with both ERK2 and ERK1, downstream effectors of the MAPK signaling cascade. We have further found that an inhibitor of MAPK signaling dramatically inhibits renal epithelial cell migration and branching morphogenesis. Thus, we believe that a novel interaction between Gabl and the MAPK signaling cascade regulates epithelial morphogenesis. We propose to investigate this hypothesis by first utilizying bacterially expressed Gab1 met binding domain to determine how ERK phosphorylation regulates the MBD-ERK association (Specific Aim la). A degenerate phosphopeptide library will be utilized to examine the possibility that the MBD represents a novel phosphoamino acid binding domain for regulating signaling protein interactions, and to determine the preferred MBD-binding sequence and thus potentially identify novel target signaling proteins for Gabl binding (Specific Aim lb). The regulation of the MBDERK2 interaction in the intact cell will next be examined by determining how growth factor addition alters Gabl-ERK2 association (Specific Aim 1c). The results of Specific Aim 1 will then be used to determine how the Gabl-MAPK interaction affects cell signaling. The ability of Gabl to regulate ERK2 kinase activity and/or specificity will be examined (Specific Aim 2a), as will the possibility that Gab1 phosphorylation by ERK2 regulates Gab1 mediated signaling protein interactions (Specific Aim 2b). Finally, the phenotypic outcome of the regulation of signaling proteins by the Gab1-ERK interaction as identified in Specific Aim 2 will be investigated utilyzing the cell lines developed in Specific Aims 1 and 2 to perform cell migration and tubulogenesis assays aimed at determining how these signaling cascades mediate renal epithelial morphogenesis (Specific Aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOCIAL SUPPORT AND DEPRESSION AMONG DIALYSIS PATIENTS Principal Investigator & Institution: Brown, Stephanie L.; Survey Research Center; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The proposed three-year research and training plan is designed to foster the academic development of the candidate in preparation for her career as a translation research scientist. Specifically, the plan is intended to (a) foster the candidate's transition from conducting experimental research on interpersonal relationships to conducting pre-intervention research on depression in chronically ill populations and (b) enable the candidate to design an intervention for depression that is informed by her program of research. The research plan is described below. The purpose of the proposed research project is to identify malleable factors that influence depression among patients undergoing dialysis therapy for renal failure. We direct special focus on the exchange of emotional and practical support between dialysis patients and their caregivers in order to isolate the unique effects of giving and receiving. We intend to examine whether giving has beneficial effects for the giver, and whether receiving has adverse effects for recipients who feel like a burden. These possibilities have typically been overlooked. Instead, investigations have focused on the benefits of receiving support from relationship partners (House, Landis, & Umberson, 1988). A longitudinal study consisting of two waves of data collection--baseline and an eight-month follow-up-is proposed to examine the unique effects of giving and receiving social support, feeling like a burden, and a number of other personality and relationship measures on depression, health, and well-being. 160 dialysis patients within the University of Michigan Health Care System will be invited to participate in two 1hour interviews over the course of eight months. Participants will be asked to respond to questions about their current mental health status (e.g., depression, anxiety), and about their relationship to a caregiver (e.g., social bonds, the exchange of social support). In addition, caregiver reports and medical records indicating patient health and compliance will be correlated with interpersonal relationship measures. The results of this project will be used to develop and test a mental health intervention for dialysis patients that takes into consideration the potential risks and benefits of social support. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND FUNCTION OF BETA2 INTEGRIN Principal Investigator & Institution: Arnaout, M Amin.; Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-MAR-2006 Summary: (provided by applicant): beta2 integrins are the major integrins expressed on leukocytes. They mediate the divalent-cation dependent adhesion functions of these cells including leukocyte homing, firm adhesion, migration, and clearance of pathogens through phagocytosis and cell-mediated killing. beta2 integrins also contribute to injury in many noninfectious diseases where the receptors are pathologically activated; these include heart attacks renal failure, allograft rejection, strokes and diabetic complications. beta2 integrins have thus become very important therapeutic targets in inflammation, autoimmunity and transplantation. The divalent cation-dependent interaction of b2 integrins with their physiologic ligands is tightly regulated by an "inside-out" activation process triggered intracellularly. It results through poorly

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understood extracellular conformational changes, in making these receptors ligandcompetent. We have traced a component of this conformational change to a major ligand-binding A-domain present in one-half of al integrin alpha subunits, including all beta integrins. We first isolated this domain in a functionally active state determined the crystal structure of its two conformations and showed that these correspond to the low and high affinity states of this domain. More recently, stable and soluble low and high affinity forms of the domain were produced and shown to interact differentially with novel ligands: interaction of the domain with some ligands required activation but that with others did not. The structural basis of these interactions is unknown. We have also solved the crystal structure of a smaller integrin (lacking the aA-domain). We now propose to structurally characterize the interaction of the low and high affinity states of the aA-domain ir complex with activation-dependent and independent ligands and begin to put this information in the wide structural context of a whole integrin by deriving the crystal structure of an integrin containing the A-domain. The beta2 integrin CD11b/CD18, the most abundant integrin of phagocytes, will continue to be the focus of our studies. Results from these studies will have profound impact on understanding the inner workings of A domain containing integrins, and consequently on the regulation of cell adhesion-dependent functions. It should also facilitate rational drug design for this class of therapeutic targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUB-OPTIMAL PRE-ESRD CARE AND ITS IMPACT ON OUTCOMES Principal Investigator & Institution: Kausz, Annamaria T.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-DEC-2004 Summary: (adapted from the application) The prevalence of end-stage renal disease (ESRD) continues to increase, and mortality among ESRD patients remains high. The principal hypothesis of this proposal is that care of patients with chronic renal failure prior to ESRD (pre-ESRD) is sub-optimal, and this adversely influences outcomes after initiation of ESRD therapy, such as morbidity, mortality and cost. The research will include a macro viewpoint using data from large databases such as the United States Renal Data System (USRDS) and Health Care Financing Administration (HCFA), and a micro viewpoint using detailed primary data collection at a single tertiary care hospital-New England Medical Center (NEMC). USRDS and HCFA files will be used to determine the prevalence and predictors of malnutrition, anemia, late initiation of dialysis and delayed referral to the nephrologist, and their impact on subsequent clinical variables. Separate analyses of pediatric and transplant patients will be undertaken, and compared with dialysis patients. NEMC data will be used to study the impact of delayed nephrology referral and delayed vascular access placement on hospitalization and cost. The results of this proposal are expected to provide important information regarding pre-ESRD care, and for the development of strategies to improve ESRD outcomes. The principal investigator has designed a comprehensive series of studies to evaluate the hypotheses enunciated in this proposal, and is well qualified to carry them through to completion. In addition to a combined fellowship in Adult and Pediatric Nephrology, she holds a Master's degree in Epidemiology. She is mentored by investigators with extensive experience in clinical investigation and advised by a panel of world leaders in epidemiology, clinical trials and health services research. Within a limited time, she and her mentor have put together an infrastructure tailored to achieve the goals of this proposal. The practical experience from the research proposed, and the comprehensive education program outlined are expected to build on the candidate's

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current skills and experience, and facilitate her transition to an independent investigator in Pediatric and Adult Renal epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TAKE CONTROL OF YOUR BLOOD PRESSURE (TCYB) STUDY Principal Investigator & Institution: Bosworth, Hayden B.; Associate Research Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The goal of this study is to improve patients' management of their hypertension. We will examine the impact of a nurse administered tailored intervention and home blood pressure (BP) monitor on BP control. This 5-year randomized controlled trial will occur in a primary care setting among diagnosed hypertensive patients. The nurse-administered intervention is based on the principles of the Health Decision Model and is designed to increase awareness, yet be easily implemented in patient care so as to enhance adherence with the prescribed regimen. The use of home BP monitors has been found to be associated with increased self management, adherence, and improved BP control. Elevated BP levels are a major risk factor for stroke, CAD, CHF, and renal disease. However, stroke rates are no longer improving and CHF and renal failure continue to increase in the U.S. Despite the high prevalence of hypertension, only approximately 25 percent of all hypertensive patients have adequate BP control. This study will be an important step in testing the effectiveness of both a nurse and self-administered intervention to improve BP control in a community sample of hypertensive patients. We will obtain consent from 570 hypertensive patients from 2 large primary care clinics and randomly assign them to receive the nurse intervention alone, home monitoring alone, bothinterventions, or usual care. Based on baseline needs assessment, patients randomized to the nurseadministered tailored intervention will receive a telephone behavioral education intervention to promote adherence with medication, including support and reminders, information on the risks of hypertension, health behaviors, patient/provider communication, literacy, and side effects at periodic telephone contacts. Patients will receive continuous patient education and will be monitored and supported to enhance adherence. Patients assigned to the home BP monitors will record their BP every other day and mail this material to the investigators. The primary outcome will be dichotomous, representing whether or not the patient's BP is > 140/90 mm/Hg (nondiabetic) and >130/85 mm/Hg (diabetics) at six month interval outpatient measurements over 24 months (5 total measurements). Descriptive statistics will be computed for all study variables stratified by treatment group. Because each patient may have a different number of observations over time, we will model the responses and evaluate the interventions using a mixed effects model for dichotomous outcomes. Based upon preliminary data, this study is expected to improve patients' management of their hypertension, decrease health care utilization and subsequently improve BP control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TGF-BETA1, RENAL DISEASE AND HYPERTENSION Principal Investigator & Institution: August, Phyllis; Professor of Medicine; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005

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Summary: Dr. Phyllis August's application for a K24 is based on her accomplishments as an investigator in patient oriented research, her significant track record of mentoring young investigators, and the research plan that explores an exciting new area of investigation in hypertension and renal disease in humans. Dr. August's past research has focused on hypertension and renal disease, especially hypertensive disorders in pregnancy. She has made original and significant discoveries with respect to regulation of blood pressure and calcium metabolism in normal and hypertensive pregnancy, and recently discovered that transforming growth factor-beta1 (TGF-beta1) is hyperexpressed in hypertensives. Also, TGF- beta1 was hyperexpressed in Africa Americans with hypertension and/or renal disease compared to their Caucasian counterparts. The research proposed for this award explores the role of TGF-beta1 hyperexpression in the pathogenesis of renal disease and hypertension. The objective of this research is to test the hypothesis that hyperexpression of TGF-beta1, a multifunctional cytokine clearly shown to induce renal disease in experimental models, is a risk factor for the progression of renal disease to end stage renal disease (ESRD) in humans. That TGF-beta1 overexpression is more frequent in African Americans, a population at greater risk for ESRD than Caucasians, and that TGF-beta1 expression is determined by TGF-beta1 DNA polymorphisms will be explored in this study with conceptually interrelated clinical and laboratory studies. Dr. August will have the primary responsibility for these studies in the next 5 years. Studies suitable for beginning investigators to develop research careers are also proposed and include, 1) investigation of TGF-beta1 as a therapeutic target for angiotensin II receptor blockade, 2) characterization of placental cytokine gene expression profiles in normal and hypertensive pregnancy, 3) clinical studies of human renovascular hypertension. Further goals include obtaining additional training in research methodology, biostatistics, and genetic epidemiology. A long-term goal is to further develop the research program in hypertensive disorders of pregnancy by training young investigators. The resources and environment at Cornell including the laboratory expertise of Dr. Suthanthiran, the broad based patient population available via the Hypertension Center and by the applicant's joint appointment in Obstetrics, the established clinical research programs (including GCRC) together provide the necessary environment to conduct the proposed research and provide mentoring to new investigators. The K24 award will provide invaluable protected time for the development of the above research protocols, for obtaining new research skills, and for ensuring the mentoring of new investigators who will continue to conduct patient oriented research in the field of kidney disease, hypertension, and hypertension in pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TISSUE SPECIFIC NUTRITIONAL ADAPTATIONS IN RENAL FAILURE Principal Investigator & Institution: Price, S Russ.; Associate Professor; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAY-2004 Summary: The essential branched-chain amino acids (BCAA) play critical roles in maintaining normal protein homeostasis and they influence critical intracellular signaling pathways that regulate metabolic functions. In normal individuals, nutritional adaptations to a reduced dietary protein intake (e.g., fasting, a low protein diet prescription) decrease the irreversible degradation of BCAA. Catabolic conditions like chronic renal failure (CRF) or acute diabetes impair these adaptive responses that

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preserve protein mass, thus contributing to the loss of lean body mass. The goals of Dr. Price and colleagues are to understand the mechanisms that regulate the activity of branched-chain alpha-ketoacid dehydrogenase (BCKAD), the rate-limiting enzyme in BCAA degradation, in the major tissues where BCAA are catabolized, and to determine if there are common signals in different catabolic states that regulate BCKAD activity, and hence, BCAA levels. To address these goals, the investigators will evaluate three hypotheses: 1) Acidification and glucocorticoids influence transcription of BCKAD subunit genes through specific cis-acting response elements. The investigators will identify specific DNA promoter elements in the BCKAD E2 gene that confer responses to acidification and glucocorticoids. 2) Abnormalities in BCAA utilization in rats with CRF result from tissue-specific alterations in BCKAD activity at both genetic and biochemical levels. The investigators will define how CRF influences the activities of BCKAD and BCKAD kinase, a unique kinase that inhibits BCKAD activity, in muscle, liver and kidney in a well-established rat model. They will measure BCKAD activity, BCKAD subunit and kinase proteins and amounts of subunit and kinase mRNAs 3) Insulin modulates BCKAD and/or BCKAD activities in different tissues by a mechanism requiring the critical signaling enzyme phosphatidylinositol 3-kinase. The investigators will determine the biochemical mechanism(s) that increase BCKAD activity in rat muscle, liver and kidney in response to acute diabetes mellitus (i.e., insulin insufficiency) and then examine the signaling mechanisms by which insulin regulates BCKAD and BCKAD kinase in cultured L6 muscle cells. The investigators findings will define cellular mechanisms regulating BCAA degradation in uremia, acute diabetes and other catabolic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOWARDS RENAL REGENERATION Principal Investigator & Institution: Little, Melissa; University of Queensland Cumbrae Stewart Building Brisbane, Queensland, 4072 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Chronic renal failure is both devastating to the individual and expensive to treat. In 1998, there were 87,000 new cases of end-stage renal disease (ESRD) in the US, taking the total patient number to 400,000. This resulted in 63,000 deaths and cost $US16.74 billion. Current treatment options for ESRD are dialysis and renal transplantation. Dialysis is expensive (($USD15-25,000/year/patient), results in a poor quality of life and a high yearly mortality rate ((16%). Kidney transplantation, although requiring immunosuppression, is preferable to dialysis, but due to a decrease in cadaveric donors worldwide only a quarter of patients awaiting transplantation will receive this treatment. Compounding the problem is a steady increase in the rate of ESRD worldwide primarily due to an increase in Type II diabetes. Several alternative treatment options are being investigated to treat chronic renal disease, including pig xenotransplantation and bioartificial kidney devices. In this application we will investigate the ability to treat chronic renal disease using stem cells. Two long-term approaches to renal regeneration will be investigated: de novo renal generation and endogenous renal repair. Both of these will require the induction of embryonic or adult stem cells to adopt a renal progenitor fate and then the isolation of these cells via specific markers. De novo generation of a replacement organ would then involve aggregation of renal progenitors and implantation of these aggregates into the omentum for vascularisation, together with reconnection to the excretory tract via a replacement ureter. Endogenous renal repair would involve the reintroduction and integration of induced and isolated renal progenitor cells into the damaged kidney. To

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reach these clinical objectives, we propose the following basic research objectives: (1) Use expression profiling to further dissect the processes of commitment to a renal fate during normal development;(2) Examine the potential for embryonic and adult stem cells to be differentiated into the lineages necessary for renal regeneration; (3) Identify novel renal progenitor cell markers and growth factors to assist in the identification, isolation and / or reactivation of renal stem cells; and (4) Utilize pathological and functional assays to determine the in vivo outcomes of de novo organ generation and renal repair. Human ES cell work will be performed using ES01, 02, 03, 04, 05 & 06 listed on the NIH ES cell line registry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “renal failure” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for renal failure in the PubMed Central database: •

Acid --base status of critically ill patients with acute renal failure: analysis based on Stewart --Figge methodology. by Rocktaeschel J, Morimatsu H, Uchino S, Goldsmith D, Poustie S, Story D, Gutteridge G, Bellomo R.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=270700

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Acute Renal Failure in an Infant Associated with Cytotoxic Aeromonas sobria Isolated from Patient's Stool and from Aquarium Water as Suspected Source of Infection. by Filler G.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88758

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Acute renal failure induced by topical ketoprofen. by Krummel T, Dimitrov Y, Moulin B, Hannedouche T.; 2000 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27256

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Acute, rapidly progressive renal failure with simultaneous use of amphotericin B and pentamidine. by Antoniskis D, Larsen RA.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171617

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Cardiac troponin T levels in patients with renal failure. by Chen BH.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122035

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

CARDIOGENIC ACUTE RENAL FAILURE (CARF) FOLLOWING OPEN-HEART SURGERY. by Barcenas CG, Jones P, Solomon S, Van Reet R, Cooley DA.; 1979 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287798

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Evaluation of cefoxitin nephrotoxicity in experimentally induced renal failure. by Ormrod DJ, Miller TE.; 1981 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181350

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Hepatocyte Growth Factor Prevents Acute Renal Failure of Accelerates Renal Regeneration in mice. by Kawaida K, Matsumoto K, Shimazu H, Nakamura T.; 1994 May 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43784

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Hypoxanthine-arabinoside pharmacokinetics after adenine arabinoside administration to a patient with renal failure. by Aronoff GR, Szwed JJ, Nelson RL, Marcus EL, Kleit SA.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283968

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Inactivation of amikacin and gentamicin by carbenicillin in patients with end-stage renal failure. by Blair DC, Duggan DO, Schroeder ET.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183751

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Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. by Jankowski J, van der Giet M, Jankowski V, Schmidt S, Hemeier M, Mahn B, Giebing G, Tolle M, Luftmann H, Schluter H, Zidek W, Tepel M.; 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164281

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Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats. by NouailleDegorce B, Veau C, Dautrey S, Tod M, Laouari D, Carbon C, Farinotti R.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105402

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Influence of Renal Failure on Intestinal Clearance of Ciprofloxacin in Rats. by Dautrey S, Rabbaa L, Laouari D, Lacour B, Carbon C, Farinotti R.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89180

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Kinetic disposition of intravenous ceftriaxone in normal subjects and patients with renal failure on hemodialysis or peritoneal dialysis. by Ti TY, Fortin L, Kreeft JH, East DS, Ogilvie RI, Somerville PJ.; 1984 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185440

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Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure. by Level C, Chauveau P, Guisset O, Cazin MC, Lasseur C, Gabinsky C, Winnock S, Montaudon D, Bedry R, Nouts C, Pillet O, Benissan GG, Favarel-Guarrigues JC, Castaing Y.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=374372

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Ofloxacin pharmacokinetics in renal failure. by Fillastre JP, Leroy A, Humbert G.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174682

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Pathogenetic Role of Arg-Gly-Asp-Recognizing Integrins in Acute Renal Failure. by Goligorsky MS, DiBona GF.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46789

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Pharmacokinetic-Pharmacodynamic Modeling of Electroencephalogram Effect of Imipenem in Rats with Acute Renal Failure. by Dupuis A, Limosin A, Paquereau J, Mimoz O, Couet W, Bouquet S.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90879

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Pharmacokinetics of a New Carbapenem, DA-1131, after Intravenous Administration to Rats with Uranyl Nitrate-Induced Acute Renal Failure. by Kim SH, Shim HJ, Kim WB, Lee MG.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105781

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Pharmacokinetics of cefaclor in renal failure: effects of multiple doses and hemodialysis. by Spyker DA, Gober LL, Scheld WM, Sande MA, Bolton WK.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181873

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Pharmacokinetics of ceftriaxone in patients with renal failure and in those undergoing hemodialysis. by Cohen D, Appel GB, Scully B, Neu HC.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185368

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Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration. by Krueger WA, Schroeder TH, Hutchison M, Hoffmann E, Dieterich HJ, Heininger A, Erley C, Wehrle A, Unertl K.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105844

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Pharmacokinetics of moxalactam in patients with renal failure and during hemodialysis. by Srinivasan S, Neu HC.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181708

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Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis. by Giron JA, Meyers BR, Hirschman SZ, Srulevitch E.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181409

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Pharmacokinetics of teicoplanin in renal failure. by Falcoz C, Ferry N, Pozet N, Cuisinaud G, Zech PY, Sassard J.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174914

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Pharmacokinetics, protein binding, and predicted extravascular distribution of moxalactam in normal and renal failure subjects. by Peterson LR, Bean B, Fasching CE, Korchik WP, Gerding DN.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181704

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Pharmacology of Cefaclor in Normal Volunteers and Patients with Renal Failure. by Santoro J, Agarwal BN, Martinelli R, Wenger N, Levison ME.; 1978 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352368

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Piperacillin pharmacokinetics in subjects with chronic renal failure. by Thompson MI, Russo ME, Matsen JM, Atkin-Thor E.; 1981 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181452

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Potential Benefit of Plasma Exchange in Treatment of Severe Icteric Leptospirosis Complicated by Acute Renal Failure. by Tse KC, Yip PS, Hui KM, Li FK, Yuen KY, Lai KN, Chan TM.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119963

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Questionnaire study and audit of use of angiotensin converting enzyme inhibitor and monitoring in general practice: the need for guidelines to prevent renal failure. by Kalra PA, Kumwenda M, MacDowall P, Roland MO.; 1999 Jan 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27706

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Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure. by Konishi K, Suzuki H, Saruta T, Hayashi M, Deguchi N, Tazaki H, Hisaka A.; 1991 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245229

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Role of Glutathione in an Animal Model of Myoglobinuric Acute Renal Failure. by Abul-Ezz SR, Walker PD, Shah SV.; 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52815

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Shiga Toxin-Producing Escherichia coli-Associated Kidney Failure in a 40-Year-Old Patient and Late Diagnosis by Novel Bacteriologic and Toxin Detection Methods. by Teel LD, Steinberg BR, Aronson NE, O'Brien AD.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165378

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The lack of a functional p21 WAF1 /CIP1 gene ameliorates progression to chronic renal failure. by Megyesi J, Price PM, Tamayo E, Safirstein RL.; 1999 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17968

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Variations in the lipid profile of patients with chronic renal failure treated with pyridoxine. by de Gomez Dumm NT, Giammona AM, Touceda LA.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=222990

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals.

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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To generate your own bibliography of studies dealing with renal failure, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “renal failure” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for renal failure (hyperlinks lead to article summaries): •

A 67 year old woman with renal failure and sinus bradycardia. Author(s): Williams SG, Bird M, Currie P. Source: Postgraduate Medical Journal. 2004 January; 80(939): 46, 48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760183

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A 74-year-old man with bilateral pulmonary opacities and rapidly progressive renal failure. Author(s): Maimon N, Abu-Shakra M, Sion-Vardi N, Almog Y. Source: Chest. 2003 December; 124(6): 2384-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665525

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A case of acute renal failure, rhabdomyolysis and disseminated intravascular coagulation associated with scrub typhus. Author(s): Lee S, Kang KP, Kim W, Kang SK, Lee HB, Park SK. Source: Clinical Nephrology. 2003 July; 60(1): 59-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872861

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A case of exercise-induced acute renal failure in a patient with idiopathic renal hypouricemia developed during antihypertensive therapy with losartan and trichlormethiazide. Author(s): Ito O, Hasegawa Y, Sato K, Mitsui H, Yuda F, Sato H, Ito S, Kudo K. Source: Hypertens Res. 2003 June; 26(6): 509-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12862209

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A patient with classical polyarteritis nodosa evolving into end stage renal failure. Author(s): Kamali S, Gul A, Poyanli A, Cefle A, Sayarlioglu M, Inanc M, Aral O, Konice M. Source: Renal Failure. 2003 November; 25(6): 1037-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14669863

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A prisoner with acute renal failure. Author(s): Chan D, Sinniah R, Irish A. Source: Lancet. 2004 January 10; 363(9403): 126. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726166

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Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure. Author(s): Scholze A, Rinder C, Beige J, Riezler R, Zidek W, Tepel M. Source: Circulation. 2004 January 27; 109(3): 369-74. Epub 2004 Jan 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732754

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Acute generalized pustular psoriasis presenting with erythroderma associated with shock and acute renal failure. Author(s): Takedai T, Yamamoto I, Tokeshi J. Source: Hawaii Med J. 2003 December; 62(12): 278-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964911

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Acute renal failure associated with legionellosis. Author(s): Brewster UC. Source: Annals of Internal Medicine. 2004 March 2; 140(5): 406-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996690

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Acute renal failure associated with tenofovir treatment in a patient with acquired immunodeficiency syndrome. Author(s): Schaaf B, Aries SP, Kramme E, Steinhoff J, Dalhoff K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): E41-3. Epub 2003 July 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884188

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Acute renal failure due to carnitine palmitoyltransferase II deficiency. Author(s): Uzel B, Altiparmak MR, Ataman R, Serdengecti K. Source: The Netherlands Journal of Medicine. 2003 December; 61(12): 417-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025419

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Acute renal failure due to hypertension: malignant hypertension in an adolescent. Author(s): Tanaka H, Tateyama T, Suzuki K, Nakahata T, Kudo M, Takahashi Y, Ito E, Waga S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 June; 45(3): 342-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828593

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Acute renal failure in a hypothyroid patient with rhabdomyolysis. Author(s): Kar PM, Hirani A, Allen MJ. Source: Clinical Nephrology. 2003 December; 60(6): 428-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690261

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Acute renal failure in coronary artery bypass surgery: independent effect of cardiopulmonary bypass. Author(s): Stallwood MI, Grayson AD, Mills K, Scawn ND. Source: The Annals of Thoracic Surgery. 2004 March; 77(3): 968-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992908

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Acute renal failure in patients with glomerular diseases: a consequence of tubular cell damage caused by haematuria? Author(s): Feith GW, Assmann KJ, Wetzels JF. Source: The Netherlands Journal of Medicine. 2003 April; 61(4): 146-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12852725

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Acute renal failure in Plasmodium vivax malaria. Author(s): Prakash J, Singh AK, Kumar NS, Saxena RK. Source: J Assoc Physicians India. 2003 March; 51: 265-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839348

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Acute renal failure on immune reconstitution in an HIV-positive patient with miliary tuberculosis. Author(s): Jehle AW, Khanna N, Sigle JP, Glatz-Krieger K, Battegay M, Steiger J, Dickenmann M, Hirsch HH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 February 15; 38(4): E32-5. Epub 2004 January 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765361

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Acute renal failure. Author(s): Weinmann ME. Source: Emerg Med Serv. 2003 December; 32(12): 71-4, 76-8, 80-2; Quiz 84. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710558

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Acute renal failure: recognition and treatment in ward patients. Author(s): Redmond A, McDevitt M, Barnes S. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2004 February 11-17; 18(22): 46-53; Quiz 54-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999985

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Atherosclerosis in renal failure. Author(s): Shoji T, Nishizawa Y. Source: Intern Med. 2003 November; 42(11): 1061-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686741

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Behcet's disease and renal failure. Author(s): Akpolat T, Diri B, Oguz Y, Yilmaz E, Yavuz M, Dilek M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 May; 18(5): 88891. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686660

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Beneficial effects of continuous overnight catheter drainage in children with polyuric renal failure. Author(s): Montane B, Abitbol C, Seeherunvong W, Chandar J, Strauss J, Gonzalez R, Zilleruelo G. Source: Bju International. 2003 September; 92(4): 447-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930438

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Benign intracranial hypertension in a patient with chronic renal failure, precipitated by hemodialysis. Author(s): Shaw D, Priestman W, McIntyre CW. Source: Clinical Nephrology. 2002 December; 58(6): 458-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508970

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Best evidence in anesthetic practice. Prevention: dopamine does not prevent death, acute renal failure, or need for dialysis. Author(s): Bracco D, Parlow JL. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 April; 49(4): 417-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927484

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Beta-2 microglobulin and serum creatinine for differentiating between immunoactivation and renal failure after liver transplantation. Author(s): Erez E, Ben-Ari Z, Sharoni E, Aravot D, Sahar G, Tur-Kaspa R, Vidne BA, Erman A. Source: Transplantation Proceedings. 2001 September; 33(6): 2920-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11543790

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Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure. Author(s): McGregor DO, Dellow WJ, Robson RA, Lever M, George PM, Chambers ST. Source: Kidney International. 2002 March; 61(3): 1040-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11849459

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Bilateral giant macular hole in a patient with chronic renal failure. Author(s): Ozdek SC, Pehlivanli Z, Sari A, Hasanreisoglu B. Source: Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. 2003 November-December; 34(6): 480-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620755

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Bilateral hydroureter and hydronephrosis causing renal failure due to a procidentia uteri: a case report. Author(s): Sudhakar AS, Reddi VG, Schein M, Gerst PH. Source: Int Surg. 2001 July-September; 86(3): 173-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996075

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Bilateral renal oncocytosis with renal failure. Author(s): Campodonico F, Carmignani G, Toncini C. Source: Archives of Pathology & Laboratory Medicine. 2002 June; 126(6): 648-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087966

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Biochemical screening for Down syndrome in renal failure. Author(s): Lam CM, Wong SF, Chow KM. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 597; Author Reply 597. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592277

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Bismuth subcitrate nephrotoxicity. A reversible cause of acute oliguric renal failure. Author(s): Sarikaya M, Sevinc A, Ulu R, Ates F, Ari F. Source: Nephron. 2002 April; 90(4): 501-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961412

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BK and JC polyomavirus infection in a patient with chronic lymphocytic leukaemia and renal failure. Author(s): Fogazzi GB, Furione M, Saglimbeni L, Gatti M, Cantu M, Tarantino A. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 August; 17(8): 1534-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147812

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BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation. Author(s): Iwamoto S, Azuma E, Hori H, Hirayama M, Kobayashi M, Komada Y, Nishimori H, Miyahara M. Source: Pediatric Hematology and Oncology. 2002 June; 19(4): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12051592

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91

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Blood pressure and melatonin in chronic renal failure. Author(s): Viljoen M, Levay PF, van Rensburg BW. Source: Clinical Nephrology. 2001 August; 56(2): 177-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522098

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Blood pressure response to conventional and low-dose enalapril in chronic renal failure. Author(s): Elung-Jensen T, Heisterberg J, Kamper AL, Sonne J, Strandgaard S. Source: British Journal of Clinical Pharmacology. 2003 February; 55(2): 139-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580985

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Blood volume monitoring in intermittent hemodialysis for acute renal failure. Author(s): Tonelli M, Astephen P, Andreou P, Beed S, Lundrigan P, Jindal K. Source: Kidney International. 2002 September; 62(3): 1075-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164893

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Body proportions before and during growth hormone therapy in children with chronic renal failure. Author(s): de Graaff LC, Mulder PG, Hokken-Koelega AC. Source: Pediatric Nephrology (Berlin, Germany). 2003 July; 18(7): 679-84. Epub 2003 May 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734746

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Bone alkaline phosphatase isoforms in chronic renal failure. Author(s): Torres PU. Source: Kidney International. 2002 March; 61(3): 1178-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11849476

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Bone density and heel ultrasound testing do not identify patients with dialysisdependent renal failure who have had fractures. Author(s): Jamal SA, Chase C, Goh YI, Richardson R, Hawker GA. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 April; 39(4): 843-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11920352

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Bronchiectasis-related amyloidosis as a cause of chronic renal failure. Author(s): Akcay S, Akman B, Ozdemir H, Eyuboglu FO, Karacan O, Ozdemir N. Source: Renal Failure. 2002 November; 24(6): 815-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472203

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Carbonic adsorbent AST-120 retards progression of renal failure by additive effect with ACEI and protein restriction diet. Author(s): Imai E, Takenaka M, Isaka Y, Moriyama T, Akagi Y, Kakuchi J, Fujii T, Ito T, Hori M, Horio M, Syoji T, Tsubakihara Y. Source: Clinical and Experimental Nephrology. 2003 June; 7(2): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586729

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Cardiac surgery in end-stage renal failure patients. Author(s): Sirch J, Weyand M, Pfeiffer S. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 November; 42(5): 1105-6; Author Reply 1106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582061

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Causes of renal failure in patients with type 2 diabetes mellitus. Author(s): Onuigbo MA. Source: Jama : the Journal of the American Medical Association. 2003 October 8; 290(14): 1855; Author Reply 1855-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532312

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Causes of renal failure in patients with type 2 diabetes mellitus. Author(s): Kida Y. Source: Jama : the Journal of the American Medical Association. 2003 October 8; 290(14): 1855; Author Reply 1855-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532311

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Cell cycle regulation: repair and regeneration in acute renal failure. Author(s): Price PM, Megyesi J, Safirstein RL. Source: Semin Nephrol. 2003 September; 23(5): 449-59. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680534

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Cholesterol metabolism in patients with chronic renal failure on hemodialysis. Author(s): Igel-Korcagova A, Raab P, Brensing KA, Poge U, Klehr HU, Igel M, von Bergmann K, Sudhop T. Source: Journal of Nephrology. 2003 November-December; 16(6): 850-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736012

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Choosing not to dialyse: evaluation of planned non-dialytic management in a cohort of patients with end-stage renal failure. Author(s): Smith C, Da Silva-Gane M, Chandna S, Warwicker P, Greenwood R, Farrington K. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 95(2): C40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610329

Studies

93

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Chronic nephropathies: individual risk for progression to end-stage renal failure as predicted by an integrated probabilistic model. Author(s): Dimitrov BD, Ruggenenti P, Stefanov R, Perna A, Remuzzi G. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 95(2): C47-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610330

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Chronic renal failure after transplantation of a nonrenal organ. Author(s): Campo A. Source: The New England Journal of Medicine. 2003 December 25; 349(26): 2563-5; Author Reply 2563-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699646

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Chronic renal failure after transplantation of a nonrenal organ. Author(s): Kida Y. Source: The New England Journal of Medicine. 2003 December 25; 349(26): 2563-5; Author Reply 2563-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699645

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Chronic renal failure after transplantation of a nonrenal organ. Author(s): Parikh CR, McSweeney PA. Source: The New England Journal of Medicine. 2003 December 25; 349(26): 2563-5; Author Reply 2563-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699644

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Chronic renal failure after transplantation of a nonrenal organ. Author(s): Gonwa TA, Mai ML, Klintmalm GB. Source: The New England Journal of Medicine. 2003 December 25; 349(26): 2563-5; Author Reply 2563-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695420

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Chronic renal failure in children. Author(s): Hari P, Singla IK, Mantan M, Kanitkar M, Batra B, Bagga A. Source: Indian Pediatrics. 2003 November; 40(11): 1035-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660834

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Chronic renal failure: a nonmalignant late effect of allogeneic stem cell transplantation. Author(s): Vincent F, Costa MA, Rondeau E. Source: Blood. 2003 October 1; 102(7): 2695; Author Reply 2695-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504068

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Chronic renal failure: assessing the Fatigue Severity Scale for use among caregivers. Author(s): Schneider RA. Source: Journal of Clinical Nursing. 2004 February; 13(2): 219-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723674

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Clinical management of anaemia pre-endstage renal failure. Author(s): Stevens PE, Flossmann O. Source: Clinical Medicine (London, England). 2003 November-December; 3(6): 503-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703026

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Clinical microbiological case: a necrotic skin lesion in a patient with renal failure. Author(s): Grill F, Munoz P, Jofre R, Bouza E. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 June; 9(6): 538-9, 580-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848730

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Cold visceral perfusion improves early survival in patients with acute renal failure after thoracoabdominal aortic aneurysm repair. Author(s): Hassoun HT, Miller CC 3rd, Huynh TT, Estrera AL, Smith JJ, Safi HJ. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2004 March; 39(3): 506-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981439

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Conservative management of end-stage renal failure: masterly inactivity or benign neglect? See Smith et al., pp. c40-c46. Author(s): Burns A. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 95(2): C37-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610333

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Coping with chronic renal failure in Hong Kong. Author(s): Mok E, Lai C, Zhang ZX. Source: International Journal of Nursing Studies. 2004 February; 41(2): 205-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725785

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Decreased expression of calcium receptor in parathyroid tissue in patients with hyperparathyroidism secondary to chronic renal failure. Author(s): Martin-Salvago M, Villar-Rodriguez JL, Palma-Alvarez A, Beato-Moreno A, Galera-Davidson H. Source: Endocrine Pathology. 2003 Spring; 14(1): 61-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746564

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Decreased phenobarbital absorption with charcoal administration for chronic renal failure. Author(s): Tanaka C, Yagi H, Sakamoto M, Koyama Y, Ohmura T, Ohtani H, Sawada Y. Source: The Annals of Pharmacotherapy. 2004 January; 38(1): 73-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742799

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Defining acute renal failure: physiological principles. Author(s): Bellomo R, Kellum JA, Ronco C. Source: Intensive Care Medicine. 2004 January; 30(1): 33-7. Epub 2003 November 15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618231

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Depressed cerebral oxygen metabolism in patients with chronic renal failure: a positron emission tomography study. Author(s): Kanai H, Hirakata H, Nakane H, Fujii K, Hirakata E, Ibayashi S, Kuwabara Y. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 October; 38(4 Suppl 1): S129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576938

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Determinants of arterial distensibility in patients with renal failure. Author(s): Beerenhout CM, Konings CJ, Dammers R, Rensma PL, Hoeks AP, Gladziwa U, Nieman FH, van der Sande FM, Leunissen KM, Kooman JP. Source: Nephron. Physiology [electronic Resource]. 2003; 95(3): P43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646357

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Diabetic renal failure in Texas: influence of ethnicity and household income. Author(s): Pazmino PA, Pazmino AK. Source: Tex Med. 2003 October; 99(10): 57-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14650814

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Diagnosis and therapy of coronary artery disease in renal failure, end-stage renal disease, and renal transplant populations. Author(s): Logar CM, Herzog CA, Beddhu S. Source: The American Journal of the Medical Sciences. 2003 April; 325(4): 214-27. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695727

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Dialysis membrane and modality in acute renal failure: understanding discordant meta-analyses. Author(s): Teehan GS, Liangos O, Lau J, Levey AS, Pereira BJ, Jaber BL. Source: Seminars in Dialysis. 2003 September-October; 16(5): 356-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969380

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Dialysis modalities in patients with acute renal failure. Author(s): Ozdemir FN, Akcay A, Haberal M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001; 16 Suppl 6: 1820. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11568230

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Dialysis strategies in critically ill acute renal failure patients. Author(s): Van Biesen W, Vanholder R, Lameire N. Source: Current Opinion in Critical Care. 2003 December; 9(6): 491-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639068

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Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. Author(s): Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, Baliga S, Vassalotti JA, Vlassara H. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 September; 42(3): 532-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955681

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Diuretics in critically ill patients with acute renal failure. Author(s): Emmett M. Source: Jama : the Journal of the American Medical Association. 2003 March 19; 289(11): 1379; Author Reply 1380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636450

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Diuretics in critically ill patients with acute renal failure. Author(s): Unnikrishnan D, Lanewala A, Krishnan S. Source: Jama : the Journal of the American Medical Association. 2003 March 19; 289(11): 1379-80; Author Reply 1380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636449

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Does plasma leptin concentration predict the nutritional status of hemodialyzed patients with chronic renal failure? Author(s): Chudek J, Adamczak M, Kania M, Holowiecka A, Rozmus W, Kokot F, Wiecek A. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 August; 9(8): Cr377-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942035

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Does recombinant growth hormone improve adult height in children with chronic renal failure? Author(s): Haffner D, Schaefer F. Source: Semin Nephrol. 2001 September; 21(5): 490-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559890

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Donor calculi induced acute renal failure. Author(s): Qazi YA, Ali Y, Venuto RC. Source: Renal Failure. 2003 March; 25(2): 315-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739839

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Donor lymphocyte infusion for late relapse followed by kidney transplantation for end-stage renal failure after allogeneic bone marrow transplantation for chronic myeloid leukemia. Author(s): Humblet-Baron S, Baron F, Beguin Y, Chachati A, Bury J, Morelon E, Kreis H. Source: Transplantation. 2003 November 27; 76(10): 1531-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657702

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Dosing guidelines for fluconazole in patients with renal failure. Author(s): Cousin L, Berre ML, Launay-Vacher V, Izzedine H, Deray G. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 November; 18(11): 2227-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551347

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Drug metabolism in chronic renal failure. Author(s): Pichette V, Leblond FA. Source: Current Drug Metabolism. 2003 April; 4(2): 91-103. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678690

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Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Author(s): Perazella MA. Source: The American Journal of the Medical Sciences. 2003 June; 325(6): 349-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811231

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Ear and kidney malformations with renal failure in an infant: what is the link? Author(s): Schiff M, Parchoux B, Cochat P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 August; 18(8): 1673-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897115

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Effect of chronic renal failure on nitric oxide metabolism. Author(s): Vaziri ND. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 October; 38(4 Suppl 1): S74-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576927

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Effects of manidipine and nifedipine on blood pressure and renal function in patients with chronic renal failure: a multicenter randomized controlled trial. Author(s): Bellinghieri G, Mazzaglia G, Savica V, Santoro D. Source: Renal Failure. 2003 September; 25(5): 681-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575277

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Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate. Author(s): Chung W, Kim EJ, Lee I, Kim SG, Lee MG, Kim SH. Source: Life Sciences. 2003 June 6; 73(3): 253-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757833

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Efficacy of GM-CSF as an adjuvant to hepatitis B vaccination in patients with chronic renal failure--results of a prospective, randomized trial. Author(s): Singh NP, Mandal SK, Thakur A, Kapoor D, Anuradha S, Prakash A, Kohli R, Agarwal SK. Source: Renal Failure. 2003 March; 25(2): 255-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739832

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Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis. Author(s): Yamada S, Muraoka I, Kato K, Hiromi Y, Takasu R, Seno H, Kawahara H, Nabeshima T. Source: Biological & Pharmaceutical Bulletin. 2003 June; 26(6): 872-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808303

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Enalapril-induced acute renal failure in a newborn infant. Author(s): Dutta S, Narang A. Source: Pediatric Nephrology (Berlin, Germany). 2003 June; 18(6): 570-2. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698328

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Endoscopic findings and the prevalence of Helicobacter pylori in chronic renal failure patients with dyspepsia. Author(s): Karari EM, Lule GN, McLigeyo SO, Amayo EO. Source: East Afr Med J. 2000 August; 77(8): 406-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12862061

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Endothelin antagonists in the treatment of renal failure. Author(s): Pollock DM. Source: Curr Opin Investig Drugs. 2001 April; 2(4): 513-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566009

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Endothelin-1 in chronic renal failure and hypertension. Author(s): Lariviere R, Lebel M. Source: Canadian Journal of Physiology and Pharmacology. 2003 June; 81(6): 607-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839272

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Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease. Author(s): Annuk M, Zilmer M, Fellstrom B. Source: Kidney International. Supplement. 2003 May; (84): S50-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694308

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End-stage renal failure in Lowe syndrome. Author(s): Tricot L, Yahiaoui Y, Teixeira L, Benabdallah L, Rothschild E, Juquel JP, Satre V, Grunfeld JP, Chauveau D. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 September; 18(9): 1923-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937245

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Endstage renal failure in primary antiphospholipid syndrome--case report and review of literature. Author(s): Dayal NA, Isenberg DA. Source: Rheumatology (Oxford, England). 2003 September; 42(9): 1128-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923280

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Enoxaparin in unstable angina patients with renal failure. Author(s): Collet JP, Montalescot G, Choussat R, Lison L, Ankri A. Source: International Journal of Cardiology. 2001 August; 80(1): 81-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575265

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Epidemiology of chronic renal failure in children: data from the ItalKid project. Author(s): Ardissino G, Dacco V, Testa S, Bonaudo R, Claris-Appiani A, Taioli E, Marra G, Edefonti A, Sereni F; ItalKid Project. Source: Pediatrics. 2003 April; 111(4 Pt 1): E382-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671156

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Epstein-Barr virus-associated acute renal failure: diagnosis, treatment, and follow-up. Author(s): Tsai JD, Lee HC, Lin CC, Liang DC, Chen SH, Huang FY. Source: Pediatric Nephrology (Berlin, Germany). 2003 July; 18(7): 667-74. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750978

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Epstein-Barr virus-associated intravascular large T-cell lymphoma presenting as acute renal failure in a patient with acquired immune deficiency syndrome. Author(s): Merchant SH, Viswanatha DS, Zumwalt RE, Foucar K. Source: Human Pathology. 2003 September; 34(9): 950-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562294

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Erythropoietin and renal failure. Author(s): Macdougall IC. Source: Curr Hematol Rep. 2003 November; 2(6): 459-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561389

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Evaluating the changes in alveolar permeability and lung ventilation in patients with chronic renal failure after haemodialysis using 99mTc-DTPA radioaerosol inhalation lung scan. Author(s): Kao MT, Shiau YC, Tsai JJ, Wang JJ, Ho ST, Kao A. Source: Nuclear Medicine Communications. 2003 July; 24(7): 825-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12813202

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Excellent outcome of Lamivudine treatment in patients with chronic renal failure and hepatitis B virus infection. Author(s): Schmilovitz-Weiss H, Melzer E, Tur-Kaspa R, Ben-Ari Z. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 64-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811212

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Factors affecting progression of renal failure in patients with type 2 diabetes. Author(s): Ueda H, Ishimura E, Shoji T, Emoto M, Morioka T, Matsumoto N, Fukumoto S, Miki T, Inaba M, Nishizawa Y. Source: Diabetes Care. 2003 May; 26(5): 1530-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716817

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Failed peritoneal dialysis in a dehydrated nephrotic child, in acute renal failure: a case report. Author(s): Olowu WA. Source: Niger Postgrad Med J. 2002 September; 9(3): 158-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12501270

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Familial clustering of rifampin-induced acute renal failure. Author(s): Chau CH, Yew WW, Chan CK. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2003 December; 7(12): 1210. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677899

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Familial phosphoglycerate kinase deficiency associated with rhabdomyolysis and acute renal failure: abnormality in mRNA splicing? Author(s): Spanu C, Oltean S. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 February; 18(2): 445-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12543909

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Fanconi syndrome and renal failure induced by tenofovir: a first case report. Author(s): Verhelst D, Monge M, Meynard JL, Fouqueray B, Mougenot B, Girard PM, Ronco P, Rossert J. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 December; 40(6): 1331-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12460055

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Fatal dyspnea in a patient with renal failure. Author(s): DePalo LR. Source: The Mount Sinai Journal of Medicine, New York. 2002 May; 69(3): 113-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035070

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Fatal granulomatous bronchopneumonia complicated by acute renal failure. Author(s): Onuigbo M, Hise M, Ramos E, Traong N, Amelung P, Drachenberg C. Source: Southern Medical Journal. 2002 August; 95(8): 947-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190246

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Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing didanosine. Author(s): Murphy MD, O'Hearn M, Chou S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 15; 36(8): 1082-5. Epub 2003 Apr 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684925

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Fatigue among caregivers of chronic renal failure patients: a principal components analysis. Author(s): Schneider RA. Source: Nephrology Nursing Journal : Journal of the American Nephrology Nurses' Association. 2003 December; 30(6): 629-33, 664. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730783

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Fibrinogen, inflammation and concentric left ventricular hypertrophy in chronic renal failure. Author(s): Zoccali C, Benedetto FA, Mallamaci F, Tripepi G, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Nicocia G, Buemi M. Source: European Journal of Clinical Investigation. 2003 July; 33(7): 561-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814392

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Fibrinogen, mortality and incident cardiovascular complications in end-stage renal failure. Author(s): Zoccali C, Mallamaci F, Tripepi G, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Stancanelli B, Nicocia G, Buemi M. Source: Journal of Internal Medicine. 2003 August; 254(2): 132-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859694

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Fibrinolysis in chronic renal failure, dialysis and renal transplantation. Author(s): Opatrny K Jr, Zemanova P, Opatrna S, Vit L. Source: Ann Transplant. 2002; 7(1): 34-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221902

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Final height in children with chronic renal failure who have not received growth hormone. Author(s): Andre JL, Bourquard R, Guillemin F, Krier MJ, Briancon S. Source: Pediatric Nephrology (Berlin, Germany). 2003 July; 18(7): 685-91. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750982

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Flutamide-induced acute renal failure in a patient with metastatic prostate cancer. Author(s): Altiparmak MR, Bilici A, Kisacik B, Ozguroglu M. Source: Medical Oncology (Northwood, London, England). 2002; 19(2): 117-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180480

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Folate metabolism in renal failure. Author(s): Teschner M, Kosch M, Schaefer RM. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002; 17 Suppl 5: 247. Review. Erratum In: Nephrol Dial Transplant. 2002 October; 17(10): 1862. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091603

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For debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure. Author(s): Hales CN, Ozanne SE. Source: Diabetologia. 2003 July; 46(7): 1013-9. Epub 2003 June 21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827239

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Fractional excretion of magnesium of chronic renal failure patients in Lagos, Nigeria. Author(s): Oladipo OO, Onubi J, Awobusuyi O, Afonja OA. Source: Niger Postgrad Med J. 2003 September; 10(3): 131-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692052

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Fractional excretion of sodium--a simple test for the differential diagnosis of acute renal failure. Author(s): Bhargava S, Jain A, Gupta V. Source: Clinical Nephrology. 2002 July; 58(1): 79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12141413

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Fundamental role of heme oxygenase in the protection against ischemic acute renal failure. Author(s): Akagi R, Takahashi T, Sassa S. Source: Japanese Journal of Pharmacology. 2002 February; 88(2): 127-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11928711

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Further considerations of retinopathy with renal failure. Author(s): Mohamed MD, McKibbin MA. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 659. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714427

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Gadolinium arteriography complicated by acute pancreatitis and acute renal failure. Author(s): Schenker MP, Solomon JA, Roberts DA. Source: Journal of Vascular and Interventional Radiology : Jvir. 2001 March; 12(3): 393. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11287523

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Gadolinium enhancement of cerebrospinal fluid in a patient with renal failure. Author(s): Erbay SH, Bhadelia RA. Source: Neuroradiology. 2001 November; 43(11): 1001-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11760790

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Gadolinium-based coronarography in a patient with renal failure: first clinical report. Author(s): Sarkis A, Badaoui G, Slaba S, Moussalli A, Jebara VA. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2001 September; 54(1): 68-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11553951

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Gastric emptying in renal failure patients using the 13C-octanoic acid breath test: facts and artifacts. Author(s): Maes BD, Evenepoel P, Geypens B, Rutgeerts P, Ghoos Y. Source: Perit Dial Int. 2002 November-December; 22(6): 732-3; Author Reply 734-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556082

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Gastroesophageal reflux and hyperacidity in chronic renal failure. Author(s): Fallone CA, Mayrand S. Source: Perit Dial Int. 2001; 21 Suppl 3: S295-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11887839

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Gastroesophageal reflux disease in chronic renal failure patients with upper GI symptoms: multivariate analysis of pathogenetic factors. Author(s): Cekin AH, Boyacioglu S, Gursoy M, Bilezikci B, Gur G, Akin ED, Ozdemir N, Yilmaz U. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1352-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094849

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Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Author(s): Norden AG, Lapsley M, Lee PJ, Pusey CD, Scheinman SJ, Tam FW, Thakker RV, Unwin RJ, Wrong O. Source: Kidney International. 2001 November; 60(5): 1885-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11703607

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Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure. Author(s): Yamashita Y, Tanase T, Terada Y, Tamura H, Akiba T, Inoue H, Ida T, Sasaki S, Marumo F, Nakamoto Y. Source: Intern Med. 2001 May; 40(5): 424-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11393416

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Gonadoblastoma and dysgerminoma associated with XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of Frasier syndrome. Author(s): Joki-Erkkila MM, Karikoski R, Rantala I, Lenko HL, Visakorpi T, Heinonen PK. Source: Journal of Pediatric and Adolescent Gynecology. 2002 June; 15(3): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12106750

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Grade of chronic renal failure, and acute and long-term outcome after percutaneous coronary interventions. Author(s): Reinecke H, Trey T, Matzkies F, Fobker M, Breithardt G, Schaefer RM. Source: Kidney International. 2003 February; 63(2): 696-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631136

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Granulocyte macrophage colony stimulating factor (GM-CSF) induced seroprotection in end stage renal failure patients to hepatitis B in vaccine non-responders. Author(s): Jha R, Lakhtakia S, Jaleel MA, Narayan G, Hemlatha K. Source: Renal Failure. 2001 September; 23(5): 629-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11725909

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Growth factor insensitivity in renal failure. Author(s): Rabkin R. Source: Renal Failure. 2001 May-July; 23(3-4): 291-300. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499545

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Growth hormone for children with chronic renal failure. Author(s): Vimalachandra D, Craig JC, Cowell C, Knight JF. Source: Cochrane Database Syst Rev. 2001; (4): Cd003264. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687179

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Growth hormone therapy in chronic renal failure induces catch-up of head circumference. Author(s): Van Dyck M, Proesmans W. Source: Pediatric Nephrology (Berlin, Germany). 2001 August; 16(8): 631-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11519892

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Growth hormone treatment enhances bone mineralisation in children with chronic renal failure. Author(s): Van Dyck M, Gyssels A, Proesmans W, Nijs J, Eeckels R. Source: European Journal of Pediatrics. 2001 June; 160(6): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11421415

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Growth hormone treatment in children with chronic renal failure: a meta-analysis of randomized controlled trials. Author(s): Vimalachandra D, Craig JC, Cowell CT, Knight JF. Source: The Journal of Pediatrics. 2001 October; 139(4): 560-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11598604

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Growth in children with chronic renal failure on intermittent versus daily calcitriol. Author(s): Schmitt CP, Ardissino G, Testa S, Claris-Appiani A, Mehls O. Source: Pediatric Nephrology (Berlin, Germany). 2003 May; 18(5): 440-4. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687466

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Guanine nucleotides and acute renal failure. Author(s): Weinberg JM, Venkatachalam MA. Source: The Journal of Clinical Investigation. 2001 November; 108(9): 1279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11696571

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Guideline for the management of acute renal failure. Author(s): Davison AM. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 August; 16(8): 1535. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11477148

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Halting progression of renal failure: consideration beyond angiotensin II inhibition. Author(s): Salahudeen AK. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 November; 17(11): 1871-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401837

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Hemofiltration and peritoneal dialysis in infection-associated acute renal failure. Author(s): Bazari H. Source: The New England Journal of Medicine. 2003 February 27; 348(9): 858-60; Author Reply 858-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608400

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Hemofiltration and peritoneal dialysis in infection-associated acute renal failure. Author(s): Fruchter O. Source: The New England Journal of Medicine. 2003 February 27; 348(9): 858-60; Author Reply 858-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608399

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Hemofiltration and peritoneal dialysis in infection-associated acute renal failure. Author(s): Casserly LF. Source: The New England Journal of Medicine. 2003 February 27; 348(9): 858-60; Author Reply 858-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608398

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Hemofiltration and peritoneal dialysis in infection-associated acute renal failure. Author(s): Rao PS, Modi KS. Source: The New England Journal of Medicine. 2003 February 27; 348(9): 858-60; Author Reply 858-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606745

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Hepatitis B and C and renal failure. Author(s): Zacks SL, Fried MW. Source: Infectious Disease Clinics of North America. 2001 September; 15(3): 877-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570146

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Hepatitis C virus and renal failure. Author(s): Jain AK, Fung JJ. Source: Transplantation Proceedings. 2003 February; 35(1): 416-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591467

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High levels of hCG in choriocarcinoma can result in renal failure and a false-negative pregnancy test in men. Author(s): Meyer T, Cole LA, Richman PI, Mitchell HD, Myers J, Rustin GJ. Source: Clin Oncol (R Coll Radiol). 2001; 13(4): 301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554631

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High serum concentrations of the acyclovir main metabolite 9carboxymethoxymethylguanine in renal failure patients with acyclovir-related neuropsychiatric side effects: an observational study. Author(s): Hellden A, Odar-Cederlof I, Diener P, Barkholt L, Medin C, Svensson JO, Sawe J, Stahle L. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18(6): 1135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748346

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Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin. Author(s): Naruszewicz M, Klinke M, Dziewanowski K, Staniewicz A, Bukowska H. Source: Metabolism: Clinical and Experimental. 2001 February; 50(2): 131-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11229418

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Homocysteine, folate, vitamin B12 levels, and C677T MTHFR mutation in children with renal failure. Author(s): Canepa A, Carrea A, Caridi G, Dertenois L, Minniti G, Cerone R, Canini S, Calevo MG, Perfumo F. Source: Pediatric Nephrology (Berlin, Germany). 2003 March; 18(3): 225-9. Epub 2003 February 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644913

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How acute renal failure puts the brakes on kidney function. Author(s): Campbell D. Source: Nursing. 2003 January; 33(1): 59-63; Quiz 64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544567

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Human immunodeficiency virus infection and renal failure. Author(s): Rao TK. Source: Infectious Disease Clinics of North America. 2001 September; 15(3): 833-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570144

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Hydroxyethylstarch as a risk factor for acute renal failure: is a change of clinical practice indicated? Author(s): Boldt J. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(12): 837-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12241125

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Hyperhomocysteinemia and protein damage in chronic renal failure and kidney transplant pediatric patients--Italian initiative on uremic hyperhomocysteinemia (IIUH). Author(s): Perna AF, Ingrosso D, Molino D, Galletti P, Montini G, Zacchello G, Bellantuono R, Caringella A, Fede C, Chimenz R, De Santo NG. Source: Journal of Nephrology. 2003 July-August; 16(4): 516-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696753

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Hyperkalemia, renal failure, and converting-enzyme inhibition: an overrated connection. Author(s): Garcia NH, Baigorria ST, Juncos LI. Source: Hypertension. 2001 September; 38(3 Pt 2): 639-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566947

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Hyperphosphataemia in renal failure: causes, consequences and current management. Author(s): Albaaj F, Hutchison A. Source: Drugs. 2003; 63(6): 577-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656655

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Hypertriglyceridemia in patients with chronic renal failure: possible mechanisms. Author(s): Prinsen BH, de Sain-van der Velden MG, de Koning EJ, Koomans HA, Berger R, Rabelink TJ. Source: Kidney International. Supplement. 2003 May; (84): S121-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694325

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Hypervitaminosis A and the redistribution of calcium in the neutrophil of chronic renal failure patients on maintenance hemodialysis treatment. Author(s): Koorts AM, Potgieter CD, Viljoen M. Source: Clinical Nephrology. 2002 September; 58(3): 249-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356198

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Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure. Author(s): Nagai T, Imamura M, Iizuka K, Mori M. Source: Diabetes Research and Clinical Practice. 2003 March; 59(3): 191-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590015

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Ibuprofen and acute renal failure in a toddler. Author(s): Moghal NE, Hegde S, Eastham KM. Source: Archives of Disease in Childhood. 2004 March; 89(3): 276-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977711

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Imaging of bone in the diagnostics of renal osteodystrophy in children with chronic renal failure. Author(s): Ziolkowska H, Panczyk-Tomaszewska M, Majkowska Z, Rajkowski T, Debinski A, Przedlacki J, Sawicki A, Ostrowski K, Marcinski A, Roszkowska-Blaim M. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 September-October; 7(5): 1034-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535955

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Immune response of intradermal hepatitis B vaccination at lower dose versus intramuscular vaccination at double standard dose in predialytic chronic renal failure patients. Author(s): Somboonsilp W, Eiam-Ong S, Tungsanga K, Tirawatanapong T. Source: J Med Assoc Thai. 2003 December; 86(12): 1122-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14971519

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Immunologic defects and vaccination in patients with chronic renal failure. Author(s): Pesanti EL. Source: Infectious Disease Clinics of North America. 2001 September; 15(3): 813-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570143

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Impact of serum creatinine measurement error on dose adjustment in renal failure. Author(s): Schneider V, Henschel V, Tadjalli-Mehr K, Mansmann U, Haefeli WE. Source: Clinical Pharmacology and Therapeutics. 2003 November; 74(5): 458-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586386

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Impaired tubulointerstitial expression of endothelin-1 and nitric oxide isoforms in donor kidney biopsies with postischemic acute renal failure. Author(s): Mitterbauer C, Schwarz C, Hauser P, Steininger R, Regele HM, Rosenkranz A, Oberbauer R. Source: Transplantation. 2003 August 27; 76(4): 715-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973116

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Incidence and outcome of acute renal failure complicating autologous stem cell transplantation for AL amyloidosis. Author(s): Fadia A, Casserly LF, Sanchorawala V, Seldin DC, Wright DG, Skinner M, Dember LM. Source: Kidney International. 2003 May; 63(5): 1868-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12675865

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Incidence of gallstones in chronic renal failure patients undergoing hemodialysis: experience of a center in Turkey. Author(s): Altiparmak MR, Pamuk ON, Pamuk GE, Celik AF, Apaydin S, Cebi D, Mihmanli I, Erek E. Source: The American Journal of Gastroenterology. 2003 April; 98(4): 813-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738461

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Increase in putrescine, amine oxidase, and acrolein in plasma of renal failure patients. Author(s): Sakata K, Kashiwagi K, Sharmin S, Ueda S, Irie Y, Murotani N, Igarashi K. Source: Biochemical and Biophysical Research Communications. 2003 May 23; 305(1): 143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732208

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Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. Author(s): Jankowski J, van der Giet M, Jankowski V, Schmidt S, Hemeier M, Mahn B, Giebing G, Tolle M, Luftmann H, Schluter H, Zidek W, Tepel M. Source: The Journal of Clinical Investigation. 2003 July; 112(2): 256-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865413

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Increased platelet-monocyte aggregates and cardiovascular disease in end-stage renal failure patients. Author(s): Ashman N, Macey MG, Fan SL, Azam U, Yaqoob MM. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 October; 18(10): 2088-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679485

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Indinavir nephropathy revisited: a pattern of insidious renal failure with identifiable risk factors. Author(s): Reilly RF, Tray K, Perazella MA. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 October; 38(4): E23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576910

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Influence of dialysis membranes on outcomes in acute renal failure. Author(s): Tonelli M, Pannu N, Manns B. Source: Kidney International. 2003 May; 63(5): 1957-8; Author Reply 1958. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12675882

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Influence of glucose in dialyzing fluid on purine concentrations in hemodialyzed patients with chronic renal failure. Author(s): Bober J, Kedzierska K, Safranow K, Kwiatkowska E, Jakubowska K, Herdzik E, Dolegowska B, Domanski L, Ciechanowski K. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 95(1): C31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520019

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Insulin is protein-anabolic in chronic renal failure patients. Author(s): Lim VS, Yarasheski KE, Crowley JR, Fangman J, Flanigan M. Source: Journal of the American Society of Nephrology : Jasn. 2003 September; 14(9): 2297-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937306

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Intermittent high permeability hemofiltration in septic patients with acute renal failure. Author(s): Morgera S, Rocktaschel J, Haase M, Lehmann C, von Heymann C, Ziemer S, Priem F, Hocher B, Gohl H, Kox WJ, Buder HW, Neumayer HH. Source: Intensive Care Medicine. 2003 November; 29(11): 1989-95. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955174

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Intermittent or continuous treatment of acute renal failure? Author(s): Ronco C, Pohlmeier R, Tetta C. Source: Critical Care Medicine. 2003 September; 31(9): 2417. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501985

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Interrelationship between plasma leptin concentration and severity of metabolic acidosis in haemodialysed patients with chronical renal failure. Author(s): Kokot F, Chudek J, Adamczak M, Wiecek A. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109(7): 370-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573148

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Iron management in renal failure patients--how do we achieve the best results? Author(s): De Vos JY. Source: Edtna Erca J. 2003 October-December; 29(4): 215-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14748433

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Isometric exercise increases the size of forearm veins in patients with chronic renal failure. Author(s): Leaf DA, MacRae HS, Grant E, Kraut J. Source: The American Journal of the Medical Sciences. 2003 March; 325(3): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640286

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JAMA patient page. Acute renal failure. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2002 November 27; 288(20): 2634. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444873

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Jugular vein placement of a small-caliber dual-lumen catheter in patients with chronic renal insufficiency or chronic renal failure. Author(s): McGraw JK, Silber JS, Patzik SB. Source: Journal of Vascular and Interventional Radiology : Jvir. 2001 April; 12(4): 550. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11287550

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Karyomegalic nephropathy: an uncommon cause of progressive renal failure. Author(s): Bhandari S, Kalowski S, Collett P, Cooke BE, Kerr P, Newland R, Dowling J, Horvath J. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 November; 17(11): 1914-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401846

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Kidney protection in preventing post-ischaemic renal failure during thoracoabdominal aortic aneurysm repair: does prostaglandin E1 together with cooling provide more protection than cooling alone? Author(s): Reiher L, Vosberg H, Sandmann W. Source: Vasa. Zeitschrift Fur Gefasskrankheiten. Journal for Vascular Diseases. 2001 February; 30(1): 21-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11284085

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Kidney transplantation for end-stage renal failure in liver transplant recipients with hepatitis C viral infection. Author(s): Molmenti EP, Jain AB, Shapiro R, Scantlebury V, Lee R, Totsuka E, Flohr J, Rakela J, Fung JJ. Source: Transplantation. 2001 January 27; 71(2): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213072

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Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure. Author(s): Lubrano R, Scoppi P, Barsotti P, Travasso E, Scateni S, Cristaldi S, Castello MA. Source: Pediatric Nephrology (Berlin, Germany). 2001 November; 16(11): 848-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685586

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Lack of seronegative hepatitis C virus infections in patients with chronic renal failure. Author(s): Kelley VA, Everett-Kitchens J, Brannon LE, Connor K, Martinez EJ, Pearson TC, Nolte FS. Source: Transplantation. 2002 November 27; 74(10): 1473-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451251

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Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Author(s): Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Source: Circulation. 2003 February 18; 107(6): 864-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591757

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Less is better: why venepuncture practice should be reviewed for those with endstage renal failure. Author(s): Hewart C. Source: Prof Nurse. 2003 February; 18(6): 344-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630247

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Linear IgA bullous dermatosis in a diabetic patient with chronic renal failure. Author(s): Serwin AB, Mysliwiec H, Laudanska H, Chodynicka B. Source: International Journal of Dermatology. 2002 November; 41(11): 778-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453003

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Lipid abnormalities in chronic renal failure, nephrotic syndrome and dialysis. Author(s): Kes P. Source: Acta Med Croatica. 2001; 55(4-5): 177-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398021

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Live donor renal allograft in end-stage renal failure patients from immunoglobulin A nephropathy. Author(s): Kim YS, Moon JI, Jeong HJ, Kim MS, Kim SI, Choi KH, Lee HY, Han DS, Park K. Source: Transplantation. 2001 January 27; 71(2): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213065

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Living with chronic renal failure: patients' experiences of their physical and functional capacity. Author(s): Heiwe S, Clyne N, Dahlgren MA. Source: Physiotherapy Research International : the Journal for Researchers and Clinicians in Physical Therapy. 2003; 8(4): 167-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730721

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Long-term outcome after percutaneous transluminal coronary angioplasty in patients with chronic renal failure with and without diabetic nephropathy. Author(s): Matzkies FK, Reinecke H, Regetmeier A, Breithardt G, Kerber S, Hohage H, Schaefer RM. Source: Nephron. 2001 September; 89(1): 10-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11528225

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Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure. Author(s): Reddy KS, Stablein D, Taranto S, Stratta RJ, Johnston TD, Waid TH, McKeown JW, Lucas BA, Ranjan D. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 February; 41(2): 464-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552511

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Loop diuretics for patients with acute renal failure: helpful or harmful? Author(s): Lameire N, Vanholder R, Van Biesen W. Source: Jama : the Journal of the American Medical Association. 2002 November 27; 288(20): 2599-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444868

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Low erythropoietin level can cause anemia in patients without advanced renal failure. Author(s): Ahn SH, Garewal HS. Source: The American Journal of Medicine. 2004 February 15; 116(4): 280-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969659

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Low incidence of end-stage renal disease and chronic renal failure in type 2 diabetes: a 10-year prospective study. Author(s): Bruno G, Biggeri A, Merletti F, Bargero G, Ferrero S, Pagano G, Perin PC. Source: Diabetes Care. 2003 August; 26(8): 2353-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882861

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Low molecular weight heparins in renal failure. Author(s): Von Visger J, Magee C. Source: Journal of Nephrology. 2003 November-December; 16(6): 914-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736021

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Low protein diet and ketosteril in predialysis patients with renal failure. Author(s): Tzekov VD, Tilkian EE, Pandeva SM, Nikolov DG, Kumchev EP, Manev EI, Dimitrakov DJ. Source: Folia Med (Plovdiv). 2000; 42(2): 34-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11217281

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Low response to HBsAg vaccine in chronic renal failure patients is not due to intrinsic defect of B cells. Author(s): Krishnamurthy G, Kher V, Naik S. Source: Scandinavian Journal of Urology and Nephrology. 2002; 36(5): 377-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487744

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Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal failure patients on dialysis therapy. Author(s): O'Byrne D, Devaraj S, Islam KN, Collazo R, McDonald L, Grundy S, Jialal I. Source: Metabolism: Clinical and Experimental. 2001 February; 50(2): 207-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11229431

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Lumbar muscle rhabdomyolysis as a cause of acute renal failure after Roux-en-Y gastric bypass. Author(s): Wiltshire JP, Custer T. Source: Obesity Surgery : the Official Journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. 2003 April; 13(2): 306-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740145

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Malignant hypertension presenting as hemolysis, thrombocytopenia, and renal failure. Author(s): Khanna A, McCullough PA. Source: Reviews in Cardiovascular Medicine. 2003 Fall; 4(4): 255-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674379

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Management of mild to moderate chronic renal failure. Author(s): Cairns HS. Source: Clinical Medicine (London, England). 2003 November-December; 3(6): 499-503. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703025

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Mannitol-induced acute renal failure. Author(s): Doi K, Ogawa N, Suzuki E, Noiri E, Fujita T. Source: The American Journal of Medicine. 2003 November; 115(7): 593-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599652

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Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure. Author(s): Level C, Chauveau P, Guisset O, Cazin MC, Lasseur C, Gabinsky C, Winnock S, Montaudon D, Bedry R, Nouts C, Pillet O, Benissan GG, Favarel-Guarrigues JC, Castaing Y. Source: Critical Care (London, England). 2003 December; 7(6): R160-6. Epub 2003 October 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624691

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Massive amoxycillin crystalluria causing anuric acute renal failure. Author(s): Labriola L, Jadoul M, Daudons M, Pirson Y, Lambert M. Source: Clinical Nephrology. 2003 June; 59(6): 455-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834178

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Metformin lactic acidosis, acute renal failure and rofecoxib. Author(s): Price G. Source: British Journal of Anaesthesia. 2003 December; 91(6): 909-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633764

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Metformin-associated lactic acidosis and acute renal failure in a type 2 diabetic patient. Author(s): Chu CK, Chang YT, Lee BJ, Hu SY, Hu WH, Yang DY. Source: J Chin Med Assoc. 2003 August; 66(8): 505-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604317

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Minimal change nephrotic syndrome presenting as acute renal failure. Author(s): Ahmed M. Source: Indian Pediatrics. 2003 July; 40(7): 676-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12881627

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Mobile components associated with rapidly developing mitral annulus calcification in patients with chronic renal failure: review of mobile elements associated with mitral annulus calcification. Author(s): Willens HJ, Ferreira AC, Gallagher AJ, Morytko JA. Source: Echocardiography (Mount Kisco, N.Y.). 2003 May; 20(4): 363-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848880

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Multifactorial uptake of Tc-99m methylene diphosphonate in chronic renal failure. Author(s): Taylor RE. Source: Clinical Nuclear Medicine. 2003 November; 28(11): 939-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578718

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Nanobacteria-caused mitral valve calciphylaxis in a man with diabetic renal failure. Author(s): Jelic TM, Malas AM, Groves SS, Jin B, Mellen PF, Osborne G, Roque R, Rosencrance JG, Chang HH. Source: Southern Medical Journal. 2004 February; 97(2): 194-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982274

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Natriuretic peptides and acute renal failure. Author(s): Vesely DL. Source: American Journal of Physiology. Renal Physiology. 2003 August; 285(2): F16777. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842858

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Neonatal acute renal failure secondary to maternal exposure to telmisartan, angiotensin II receptor antagonist. Author(s): Pietrement C, Malot L, Santerne B, Roussel B, Motte J, Morville P. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2003 April-May; 23(3): 254-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732865

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Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure. Author(s): Swartz RD, Crofford LJ, Phan SH, Ike RW, Su LD. Source: The American Journal of Medicine. 2003 May; 114(7): 563-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753880

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Nephroquiz: a woman with renal failure, ureteric obstruction and vasculitic rash. Author(s): Alexander JL, Rustom R, Herrington CS, Kingston RE, Bone JM. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 November; 18(11): 2439-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551383

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Nitric oxide synthesis in chronic renal failure. Are plasma S-nitrosothiol levels elevated? Author(s): Tsikas D, Frolich JC, Kielstein JT. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2004 January; 339(1-2): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687910

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Non-secretory multiple myeloma with hypercalcemic acute renal failure. Author(s): Prakash MS, Baliga KV, Singh AP, Mishra DK. Source: J Assoc Physicians India. 2002 October; 50: 1330-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12568228

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Not so acute renal failure with crystals in the urine. Author(s): Dehmel B, Schneider W, Kettritz R, Luft FC. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 January; 18(1): 209-11. Erratum In: Nephrol Dial Transplant. 2003 March; 18(3): 627. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480987

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Novel approaches to the treatment of acute renal failure. Author(s): Venkataraman R, Kellum JA. Source: Expert Opinion on Investigational Drugs. 2003 August; 12(8): 1353-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882621

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Nutrition in patients with acute renal failure. Author(s): Bozfakioglu S. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001; 16 Suppl 6: 212. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11568231

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Observations with regard to the National Kidney Foundation K/DOQI clinical practice guidelines concerning serum transthyretin in chronic renal failure. Author(s): Kopple JD, Mehrotra R, Suppasyndh O, Kalantar-Zadeh K. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 December; 40(12): 1308-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553435

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Office and ambulatory blood pressure elevation in children with chronic renal failure. Author(s): Mitsnefes MM, Kimball TR, Daniels SR. Source: Pediatric Nephrology (Berlin, Germany). 2003 February; 18(2): 145-9. Epub 2002 December 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579404

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Origin and characteristics of an unusual pyridine nucleotide accumulating in erythrocytes: positive correlation with degree of renal failure. Author(s): Carrey EA, Smolenski RT, Edbury SM, Laurence A, Marinaki AM, Duley JA, Zhu L, Goldsmith DJ, Simmonds HA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 September; 335(1-2): 117-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927693

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Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference? Author(s): Van Den Noortgate N, Mouton V, Lamot C, Van Nooten G, Dhondt A, Vanholder R, Afschrift M, Lameire N. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 April; 18(4): 732-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637642

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Outcome in severe acute renal failure associated with malaria. Author(s): Naqvi R, Ahmad E, Akhtar F, Naqvi A, Rizvi A. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 September; 18(9): 1820-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937230

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Outcomes in patients with normal serum creatinine and with artificial renal support for acute renal failure developing after coronary artery bypass grafting. Author(s): Leacche M, Rawn JD, Mihaljevic T, Lin J, Karavas AN, Paul S, Byrne JG. Source: The American Journal of Cardiology. 2004 February 1; 93(3): 353-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759390

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Outcomes research in acute renal failure. Author(s): Mehta RL. Source: Semin Nephrol. 2003 May; 23(3): 283-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838497

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Overuse of acid suppressant drugs in patients with chronic renal failure. Author(s): Strid H, Simren M, Bjornsson ES. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 March; 18(3): 570-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584281

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Overview of pediatric renal replacement therapy in acute renal failure. Author(s): Goldstein SL. Source: Artificial Organs. 2003 September; 27(9): 781-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940899

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Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane. Author(s): Westhuyzen J, Saltissi D, Stanbury V. Source: Ann Clin Lab Sci. 2003 Winter; 33(1): 3-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661892

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Patients with chronic renal failure have abnormal small intestinal motility and a high prevalence of small intestinal bacterial overgrowth. Author(s): Strid H, Simren M, Stotzer PO, Ringstrom G, Abrahamsson H, Bjornsson ES. Source: Digestion. 2003; 67(3): 129-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853724

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Peritoneal dialysis in children with acute renal failure after open heart surgery. Author(s): Lin MC, Fu YC, Fu LS, Jan SL, Chi CS. Source: Acta Paediatr Taiwan. 2003 March-April; 44(2): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845849

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Pharmacodynamic population analysis in chronic renal failure using artificial neural networks--a comparative study. Author(s): Gaweda AE, Jacobs AA, Brier ME, Zurada JM. Source: Neural Networks : the Official Journal of the International Neural Network Society. 2003 June-July; 16(5-6): 841-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850042

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Pharmacologic treatment of acute renal failure in sepsis. Author(s): De Vriese AS, Bourgeois M. Source: Current Opinion in Critical Care. 2003 December; 9(6): 474-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639066

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Prevalence of hepatitis B and C viruses in pre-dialysis patients with chronic renal failure. Author(s): Salako BL, Ayodele OE, Kadiri S, Arije A. Source: Afr J Med Med Sci. 2002 December; 31(4): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027769

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Prevention and nondialytic treatment of acute renal failure. Author(s): Lameire NH, De Vriese AS, Vanholder R. Source: Current Opinion in Critical Care. 2003 December; 9(6): 481-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639067

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Prevention of chronic renal failure at the community level. Author(s): Mani MK. Source: Kidney International. Supplement. 2003 February; (83): S86-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12864881

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Progression of chronic renal failure in focal segmental glomerulosclerosis: consequence of podocyte damage or of tubulointerstitial fibrosis? Author(s): Kriz W. Source: Pediatric Nephrology (Berlin, Germany). 2003 July; 18(7): 617-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879860

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Protein Z, a vitamin K-dependent protein in patients with renal failure. Author(s): Malyszko J, Skrzydlewska E, Malyszko JS, Mysliwiec M. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 January; 1(1): 195-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871562

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Pulmonary hypertension in patients with chronic renal failure: role of parathyroid hormone and pulmonary artery calcifications. Author(s): Amin M, Fawzy A, Hamid MA, Elhendy A. Source: Chest. 2003 December; 124(6): 2093-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665485

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QTc interval in children with chronic renal failure and with renal transplants. Author(s): Butani L, Berg G, Makker SP. Source: Pediatric Nephrology (Berlin, Germany). 2002 January; 17(1): 6-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793127

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Quality of life and dialysis decisions in critically ill patients with acute renal failure. Author(s): Maynard SE, Whittle J, Chelluri L, Arnold R. Source: Intensive Care Medicine. 2003 September; 29(9): 1589-93. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819880

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Rapidly progressive irreversible renal failure in patients with pancreatic insufficiency. Author(s): Hill P, Karim M, Davies DR, Roberts IS, Winearls CG. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 October; 42(4): 842-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520637

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Recognizing chronic renal failure.the sooner, the better. Author(s): Cannon JD. Source: Nursing. 2004 January; 34(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722435

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Reduction in natural death and renal failure from a systematic screening and treatment program in an Australian Aboriginal community. Author(s): Hoy WE, Wang Z, Baker PR, Kelly AM. Source: Kidney International. Supplement. 2003 February; (83): S66-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12864878

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Removal of expression of concern: Schiffl H, et Al. Daily hemodialysis and the outcome of acute renal failure. N Engl J Med 2002;346:305-10. Author(s): Drazen JM, Ingelfinger JR, Curfman GD. Source: The New England Journal of Medicine. 2003 November 13; 349(20): 1965. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614172

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Renal assist device therapy for acute renal failure. Author(s): Dirkes SM, Kozlowski C. Source: Nephrology Nursing Journal : Journal of the American Nephrology Nurses' Association. 2003 December; 30(6): 611-4, 619-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730781

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Renal failure and renal replacement therapy. Author(s): Maxvold NJ, Bunchman TE. Source: Critical Care Clinics. 2003 July; 19(3): 563-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848321

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Renal failure with the use of zoledronic acid. Author(s): Chang JT, Green L, Beitz J. Source: The New England Journal of Medicine. 2003 October 23; 349(17): 1676-9; Discussion 1676-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573746

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Renal replacement therapy for acute renal failure on the ICU: coming of age? Author(s): van der Klooster JM. Source: The Netherlands Journal of Medicine. 2003 December; 61(12): 430; Author Reply 431. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025421

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Renal replacement therapy for acute renal failure on the intensive care unit: coming of age? Author(s): van Bommel EF. Source: The Netherlands Journal of Medicine. 2003 August; 61(8): 239-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628958

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Retroperitoneal paraganglioma presenting with renal failure: findings on computed tomography with pathologic correlation. Author(s): Moore C, Sheth S, Steinberg D, Fishman E. Source: Critical Reviews in Computed Tomography. 2003; 44(3): 137-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877438

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Safety of new phosphate binders for chronic renal failure. Author(s): Loghman-Adham M. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(15): 1093-115. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640773

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Serum cardiac troponin and subclinical cardiac status in pediatric chronic renal failure. Author(s): Lipshultz SE, Somers MJ, Lipsitz SR, Colan SD, Jabs K, Rifai N. Source: Pediatrics. 2003 July; 112(1 Pt 1): 79-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837871

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Severe rhabdomyolysis and acute renal failure following recent Coxsackie B virus infection. Author(s): Fodili F, van Bommel EF. Source: The Netherlands Journal of Medicine. 2003 May; 61(5): 177-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916546

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Silent stroke in a case of beta-thalassemia major associated with chronic renal failure and diabetes mellitus. Author(s): Caksen H, Odabas D, Akbayram S, Faik Oner A, Arslan S, Cesur Y, Uner A. Source: Journal of Child Neurology. 2003 November; 18(11): 798-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696909

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Simultaneous hemodialysis during coronary angiography fails to prevent radiocontrast-induced nephropathy in chronic renal failure. Author(s): Frank H, Werner D, Lorusso V, Klinghammer L, Daniel WG, Kunzendorf U, Ludwig J. Source: Clinical Nephrology. 2003 September; 60(3): 176-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14524580

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Skeletal muscle and nutritional assessment in chronic renal failure patients on a protein-restricted diet. Author(s): Cupisti A, Licitra R, Chisari C, Stampacchia G, D'Alessandro C, Galetta F, Rossi B, Barsotti G. Source: Journal of Internal Medicine. 2004 January; 255(1): 115-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687247

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Small ruptured abdominal aortic aneurysm with renal failure: endovascular treatment--a case report. Author(s): Melissano G, Moura MR, Tshomba Y, Marone EM, Chiesa R. Source: Vascular and Endovascular Surgery. 2003 July-August; 37(4): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894371

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Special characteristics of atherosclerosis in chronic renal failure. Author(s): Amann K, Tyralla K, Gross ML, Eifert T, Adamczak M, Ritz E. Source: Clinical Nephrology. 2003 July; 60 Suppl 1: S13-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940530

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Successful treatment with micafungin of invasive pulmonary aspergillosis in acute myeloid leukemia, with renal failure due to amphotericin B therapy. Author(s): Yokote T, Akioka T, Oka S, Fujisaka T, Yamano T, Hara S, Tsuji M, Hanafusa T. Source: Annals of Hematology. 2004 January; 83(1): 64-6. Epub 2003 August 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14661114

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Susceptibility genes for hypertension and renal failure. Author(s): Freedman BI. Source: Journal of the American Society of Nephrology : Jasn. 2003 July; 14(7 Suppl 2): S192-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819327

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The change in renal replacement therapy on acute renal failure in a general intensive care unit in a university hospital and its clinical efficacy: a Japanese experience. Author(s): Hirayama Y, Hirasawa H, Oda S, Shiga H, Nakanishi K, Matsuda K, Nakamura M, Hirano T, Moriguchi T, Watanabe E, Nitta M, Abe R, Nakada T. Source: Therap Apher Dial. 2003 October; 7(5): 475-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708903

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The effect of hemodialysis on visual field test in patients with chronic renal failure. Author(s): Pelit A, Zumrutdal A, Akova Y. Source: Current Eye Research. 2003 May; 26(5): 303-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854059

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The longitudinal chronic kidney disease study: a prospective cohort study of predialysis renal failure. Author(s): Perlman RL, Kiser M, Finkelstein F, Eisele G, Roys E, Liu L, Burrows-Hudson S, Port F, Messana JM, Bailie G, Rajagopalan S, Saran R. Source: Seminars in Dialysis. 2003 November-December; 16(6): 418-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629599

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The pathogenesis of septic acute renal failure. Author(s): Wan L, Bellomo R, Di Giantomasso D, Ronco C. Source: Current Opinion in Critical Care. 2003 December; 9(6): 496-502. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639069

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The use of solid-state polydimethylsiloxane in the management of vesico-ureteric reflux in patients with renal failure prepared for renal transplantation. Author(s): Wadie BS, Refaie AF, Ghoneim MA. Source: Bju International. 2003 November; 92(7): 818-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616473

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Thymidine rescue: an antidote for pemetrexed-related toxicity in the setting of acute renal failure. Author(s): Castro M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 November 1; 21(21): 4066. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581433

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Tolerability and efficacy of multidose epoetin beta (Reco-Pen) for subcutaneous administration in patients with anemia due to renal failure. Author(s): Kleophas W, Kult J, Kreusser W, Piper C, Plache H, Wunderle P, Fiegel V, Hartl W; Collaborative Study Group. Source: Kidney & Blood Pressure Research. 2003; 26(3): 192-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886047

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Treatment of a patient with chronic renal failure with rituximab for a follicular lymphoma: safe and successful option of rituximab therapy. Author(s): Abdelkefi A, Mellouli F, Bejaoui M. Source: European Journal of Haematology. 2003 August; 71(2): 128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890153

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Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure. Author(s): Young PC, Hae CC, Lee KH, Hoon CJ. Source: Korean J Intern Med. 2003 December; 18(4): 248-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717236

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Twenty-eight-year-old female with primary amenorrhea and chronic renal failure: a case of Frasier syndrome? Author(s): Onyemekeihia R, Oviasu E. Source: Journal of the National Medical Association. 2004 February; 96(2): 256-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977287

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Ulcerating subcutaneous nodules and advanced renal failure: is it time for a new liver? Author(s): Karakousis PC, Tomaszewski JE. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 October; 16(10): 2095-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11572906

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Update on dialytic management of acute renal failure. Author(s): Teehan GS, Liangos O, Jaber BL. Source: Journal of Intensive Care Medicine. 2003 May-June; 18(3): 130-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984631

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Update on interleukin-6 and its role in chronic renal failure. Author(s): Pecoits-Filho R, Lindholm B, Axelsson J, Stenvinkel P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18(6): 1042-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748331

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Upper extremity bypass grafting for limb salvage in end-stage renal failure. Author(s): Chang BB, Roddy SP, Darling RC 3rd, Maharaj D, Paty PS, Kreienberg PB, Ozsvath KJ, Mehta M, Shah DM. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 December; 38(6): 1313-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681634

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Use of antibacterial agents in renal failure. Author(s): Livornese LL Jr, Slavin D, Benz RL, Ingerman MJ, Santoro J. Source: Infectious Disease Clinics of North America. 2001 September; 15(3): 983-1002, Xi. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570149

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Use of immunosuppressive drugs and lamivudine in a patient with nephrotic syndrome, severe renal failure, and HBV cirrhosis: case report. Author(s): Balal M, Seyrek N, Karayaylali I, Paydas S, Gonlusen G. Source: Adv Ther. 2003 July-August; 20(4): 191-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14669814

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Use of thalidomide in patients with myeloma and renal failure may be associated with unexplained hyperkalaemia. Author(s): Harris E, Behrens J, Samson D, Rahemtulla A, Russell NH, Byrne JL. Source: British Journal of Haematology. 2003 July; 122(1): 160-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823359

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Useful biochemical markers for diagnosing renal osteodystrophy in predialysis endstage renal failure patients. Author(s): Bervoets AR, Spasovski GB, Behets GJ, Dams G, Polenakovic MH, Zafirovska K, Van Hoof VO, De Broe ME, D'Haese PC. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 May; 41(5): 997-1007. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12722034

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Usefulness of tachycardic-stress perfusion imaging to predict coronary artery disease in high-risk patients with chronic renal failure. Author(s): Worthley MI, Unger SA, Mathew TH, Russ GR, Horowitz JD. Source: The American Journal of Cardiology. 2003 December 1; 92(11): 1318-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636911

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Usefulness of technetium-99m hexamethylpropylene amine oxime lung scan to detect subclinical lung injury in patients with chronic renal failure. Author(s): Chang CH, Wu HC, Tsai JJ, Lin CC, Lee CC, Kao A. Source: Lung. 2003; 181(2): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953148

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Valvular heart operation is an independent risk factor for acute renal failure. Author(s): Grayson AD, Khater M, Jackson M, Fox MA. Source: The Annals of Thoracic Surgery. 2003 June; 75(6): 1829-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12822624

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Variation at the beta-1 adrenoceptor gene locus affects left ventricular mass in renal failure. Author(s): Stanton T, Inglis GC, Padmanabhan S, Dominiczak AF, Jardine AG, Connell JM. Source: Journal of Nephrology. 2002 September-October; 15(5): 512-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455717

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Variations in the lipid profile of patients with chronic renal failure, treated with folic acid. Author(s): de Gomez Dumm NT, Giammona AM, Touceda LA. Source: Int J Vitam Nutr Res. 2003 May; 73(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847999

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Varicella vaccination in children with chronic renal failure. A report of the Southwest Pediatric Nephrology Study Group. Author(s): Furth SL, Hogg RJ, Tarver J, Moulton LH, Chan C, Fivush BA; Southwest Pediatric Nephrology Study Group. Source: Pediatric Nephrology (Berlin, Germany). 2003 January; 18(1): 33-8. Epub 2002 November 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488988

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Vascular calcification in chronic renal failure. Author(s): Tomson C. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 93(4): C124-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759580

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Vasoactive mediators and renal haemodynamics in exertional heat stroke complicated by acute renal failure. Author(s): Lin YF, Wang JY, Chou TC, Lin SH. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 March; 96(3): 193201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615983

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Vitamin C improves resistance but not conduit artery endothelial function in patients with chronic renal failure. Author(s): Cross JM, Donald AE, Nuttall SL, Deanfield JE, Woolfson RG, Macallister RJ. Source: Kidney International. 2003 April; 63(4): 1433-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631359

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Vitamin D deficiency: a neglected aspect of disturbed calcium metabolism in renal failure. Author(s): Cannata-Andia JB, Gomez Alonso C. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 November; 17(11): 1875-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401838

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Vitamin D receptor: mechanisms for vitamin D resistance in renal failure. Author(s): Dusso AS. Source: Kidney International. Supplement. 2003 June; (85): S6-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753256

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Vitamin K status in relation to bone metabolism in patients with renal failure. Author(s): Malyszko J, Wolczynski S, Skrzydlewska E, Malyszko JS, Mysliwiec M. Source: American Journal of Nephrology. 2002 September-December; 22(5-6): 504-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381951

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Waldenstrom's macroglobulinaemia and acute renal failure: isoosmolal non-ionic contrast medium is not an absolute contraindication. Author(s): Scarpioni R, Cristinelli L, Quaretti P, Imberti D, Cavallotti P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 May; 16(5): 1083-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328931

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Wall shear stress assessment in the common carotid artery of end-stage renal failure patients. Author(s): Samijo SK, Barkhuysen R, Willigers JM, Leunissen KM, Ledoux LA, Kitslaar PJ, Hoeks AP. Source: Nephron. 2002; 92(3): 557-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372937

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Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure. Author(s): Stemmler J, Weise A, Hacker U, Heinemann V, Schalhorn A. Source: Onkologie. 2002 February; 25(1): 60-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893885

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What is the optimal strategy to intensify blood pressure control and prevent progression of renal failure? Author(s): Epstein M, Tobe S. Source: Current Hypertension Reports. 2001 October; 3(5): 422-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11551378

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When your patient needs peritoneal dialysis. Brush up on this necessary but infrequently used skill that you may need if your patient has chronic renal failure. Author(s): Zabat E. Source: Nursing. 2003 August; 33(8): 52-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900672

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Why is there so much end-stage renal failure of undetermined cause in UK IndoAsians? Author(s): Ball S, Lloyd J, Cairns T, Cook T, Palmer A, Cattell V, Taube D. Source: Qjm : Monthly Journal of the Association of Physicians. 2001 April; 94(4): 187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11294961

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CHAPTER 2. NUTRITION AND RENAL FAILURE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and renal failure.

Finding Nutrition Studies on Renal Failure The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “renal failure” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on renal failure: •

Nutritional strategies for the treatment of chronic renal failure in children. Source: Georgalas, A. Goffi, J. Dwyer, J. Nutrition-today (USA). (August 1993). volume 28(4) page 24-28.

Additional consumer oriented references include: •

A fiber-rich diet for the treatment of diabetic patients with chronic renal failure. Source: Rivellese, A Parillo, M Giacco, A De Marco, F Riccardi, G Diabetes-Care. 1985 Nov-December; 8(6): 620-1 0149-5992

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Aluminum toxicity in children with chronic renal failure. Source: Nutrition-and-the-M.D (USA). (March 1986). volume 12(3) page 3-4. aluminium toxicity urinary tract diseases children dialysis phosphates chelating agents 0732-0167

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Effect of intensive treatment of diabetes of the risk of death or renal failure in NIDDM and IDDM. Author(s): Heart of America Diabetes Research Foundation, North Kansas City, MO 64116, USA. Source: Hellman, R Regan, J Rosen, H Diabetes-Care. 1997 March; 20(3): 258-64 01495992

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Effect of keto acid diets in chronic renal failure. Source: Anonymous Nutr-Revolume 1987 October; 45(10): 305-9 0029-6643

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Nutrition in renal failure. Source: Kurtzweil, P. Young, T.A. Nutr-Res-Rev. Cambridge [England] : Cambridge University Press. 1989. volume 2 page 1-16. 0954-4224

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Nutritional management of infants and toddlers with chronic renal failure. Author(s): Department of Paediatrics, United Medical School, Guy's Hospital, London, U.K. Source: Rigden, S P Start, K M Rees, L Nutr-Health. 1987; 5(3-4): 163-74 0260-1060

The following information is typical of that found when using the “Full IBIDS Database” to search for “renal failure” (or a synonym): •

Acute renal failure during dextran-40 antithrombotic prophylaxis: report of two microsurgical cases. Author(s): Department of Plastic and Reconstructive Surgery at Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Source: Vos, Sanne C B Hage, J Joris Woerdeman, Leonie A E Noordanus, Robert P AnnPlast-Surg. 2002 February; 48(2): 193-6 0148-7043

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Advanced glycation end products in children with chronic renal failure and type 1 diabetes. Author(s): Klinikum der FSU, Klinik fur Kinder- und Jugendmedizin, Kochstrasse 2, 07745 Jena, Germany. [email protected] Source: Misselwitz, Joachim Franke, Sybille Kauf, Eberhard John, Ulrike Stein, Gunter Pediatr-Nephrol. 2002 May; 17(5): 316-21 0931-041X

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Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases. Author(s): Department of Nephrology, Tel Aviv Medical Center, Israel. [email protected] Source: Silverberg, D S Wexler, D Blum, M Sheps, D Schwartz, D Yachnin, T Baruch, R Tchebiner, J Zubkov, A Shaked, M Steinbruch, S Keren, G Iaina, A Perit-Dial-Int. 2001; 21 Suppl 3: S236-40 0896-8608

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Circadian serum melatonin profiles in patients suffering from chronic renal failure. Author(s): Laboratory of Electron Microscopy, Chair of Pathomorphology, Medical University of Lodz, Lodz, Poland. [email protected] Source: Karasek, M Szuflet, A Chrzanowski, W Zylinska, K Swietoslawski, J Neuroendocrinol-Lett. 2002 April; 23 Suppl 1: 97-102 0172-780X

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Comparison of two micronutrient supplements in children with chronic renal failure. Author(s): Department of Dietetics and Nutrition, Nottingham City Hospital NHS Trust, Nottingham, UK. Source: Coleman, J E Watson, A R Chowdhury, S Thurlby, D Wardell, J J-Ren-Nutr. 2002 October; 12(4): 244-7 1051-2276

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Continuous haemofiltration in acute renal failure with prostacyclin as the sole antihaemostatic agent. Author(s): Dipartimento di Clinica Medica, Nefrologia & Scienze della Prevenzione, Universita degli Studi di Parma, Via Gramsci 14, 43100 Parma, Italy. [email protected] Source: Fiaccadori, E Maggiore, U Rotelli, C Minari, M Melfa, L Cappe, G Cabassi, A Intensive-Care-Med. 2002 May; 28(5): 586-93 0342-4642

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Effect of the correction of metabolic acidosis on nutritional status in elderly patients with chronic renal failure. Author(s): Department of Nephrology, Dunkerque General Hospital, Dunkerque, France. Source: Verove, C Maisonneuve, N El Azouzi, A Boldron, A Azar, R J-Ren-Nutr. 2002 October; 12(4): 224-8 1051-2276

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Effects of low-protein diet supplemented with ketoacids and erythropoietin in chronic renal failure: a long-term metabolic study. Author(s): Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine and Chain of Nephrology, Postgraduate Medical School, Prague, Czech Republic. [email protected] Source: Teplan, V Schuck, O Knotek, A Hajny, J Horackova, M Skibova, J Maly, J AnnTransplant. 2001; 6(1): 47-53 1425-9524

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Effects of the anti-ulcer agents ecabet sodium, cimetidine and sucralfate on acetylsalicylic acid-induced gastric mucosal damage deteriorated by renal failure in rats. Source:

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Endocrine abnormalities in chronic renal failure. Author(s): Department of Internal Medicine, Division of Nephrology, University of Michigan Health System, B1911 Clinical Faculty Office Building, Ann Arbor, MI 481090704, USA. [email protected] Source: Leavey, S F Weitzel, W F Endocrinol-Metab-Clin-North-Am. 2002 March; 31(1): 107-19 0889-8529

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Experimental renal failure and iron overload: a histomorphometric study in the alveolar bone of rats. Author(s): Department of Histology, School of Dentistry, University of Buenos Aires, Argentina. [email protected] Source: Mandalunis, P Gibaja, F Ubios, A M Exp-Toxicol-Pathol. 2002 August; 54(2): 8590 0940-2993

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High salt intake inhibits nitric oxide synthase expression and aggravates hypertension in rats with chronic renal failure. Author(s): Department of Medicine, Keck School of Medicine University of Southern California, Los Angeles, USA. [email protected] Source: Campese, V M Mozayeni, P Ye, S Gumbard, M J-Nephrol. 2002 Jul-August; 15(4): 407-13 1120-3625

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Hydroxyethylstarch as a risk factor for acute renal failure: is a change of clinical practice indicated? Author(s): Department of Anaesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany. [email protected] Source: Boldt, J Drug-Saf. 2002; 25(12): 837-46 0114-5916

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Immobilization-related hypercalcemia after renal failure in burn injury. Author(s): Division of Endocrinology and Metabolism, Loyola University Medical Center, Maywood, Illinois 60153, USA. Source: Peralta, M C Gordon, D L Endocr-Pract. 2002 May-June; 8(3): 213-6 1530-891X

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Increase in urea in conjunction with L-arginine metabolism in the liver leads to induction of cytochrome P450 2E1 (CYP2E1): the role of urea in CYP2E1 induction by acute renal failure. Author(s): National Research Laboratory, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, South Korea. Source: Chung, H C Kim, S H Lee, M G Kim, S G Drug-Metab-Dispos. 2002 June; 30(6): 739-46 0090-9556

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Information and counselling for patients approaching end-stage renal failure in selected centres across Europe. Author(s): Renal Unit, Lister Hospital, Stevenage, UK. Source: Da Silva Gane, Maria Goovaerts, Tony Elseviers, Monique M Lindley, Elizabeth J EDTNA-ERCA-J. 2002 Jan-Mar; 28(1): 49-55 1019-083X

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Intermediate-dose (25mg/m2) IV melphalan for multiple myeloma with renal failure. Author(s): Services of Nephrology, Edouard Herriot Hospital, Lyon, France. [email protected] Source: Vigneau, C Ardiet, C Bret, M Laville, M Fiere, D Tranchand, B Fouque, D JNephrol. 2002 Nov-December; 15(6): 684-9 1120-3625

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Isoniazid-induced seizures with secondary rhabdomyolysis and associated acute renal failure in a dog. Author(s): Ocean Avenue Veterinary Hospital, San Francisco, CA 94112, USA. Source: Haburjak, J J Spangler, W L J-Small-Anim-Pract. 2002 April; 43(4): 182-6 00224510

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Nutritional aspects of acute renal failure. Author(s): Dietetic Department, Meander Medical Centre, Amersfoort, The Netherlands. [email protected] Source: Hoogerwerf, M EDTNA-ERCA-J. 2002; Suppl 2: 54-5, 58 1019-083X

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Olfactory function in chronic renal failure. Author(s): [email protected] Source: Frasnelli, J A Temmel, A F Quint, C Oberbauer, R Hummel, T Am-J-Rhinol. 2002 Sep-October; 16(5): 275-9 1050-6586

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Oxidative stress and chronic renal failure: markers and management. Author(s): Division of Nephrology, CH Beauvais, INSERM U507, Necker Hospital, Paris, France. [email protected] Source: Massy, Z A Nguyen Khoa, T J-Nephrol. 2002 Jul-August; 15(4): 336-41 1120-3625

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Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats. Author(s): Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan. Source: Takaoka, Masanori Ohkita, Mamoru Kobayashi, Yutaka Yuba, Mikihiro Matsumura, Yasuo Clin-Exp-Pharmacol-Physiol. 2002 March; 29(3): 189-94 0305-1870

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Recombinant human growth hormone in patients with acute renal failure. Author(s): Division of Nephrology, Maine Medical Center, Portland, ME 04102, USA. Source: Saadeh, E Ikizler, T A Shyr, Y Hakim, R M Himmelfarb, J J-Ren-Nutr. 2001 October; 11(4): 212-9 1051-2276

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Reduction of plasma homocysteine by folic acid in children with chronic renal failure. Author(s): Department of Pediatrics, Seoul National University Medical School, Clinical Research Institute, Seoul National University Hospital, Korea. Source: Kang, H G Lee, B S Hahn, H Lee, J H Ha, I S Cheong, H I Choi, Y PediatrNephrol. 2002 July; 17(7): 511-4 0931-041X

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Severe chronic renal failure in association with oxycodone addiction: a new form of fibrillary glomerulopathy. Author(s): Department of Anatomical Pathology, St. Vincent's Hospital, Fitzroy, Victoria, Australia. Source: Hill, P Dwyer, K Kay, T Murphy, B Hum-Pathol. 2002 August; 33(8): 783-7 00468177

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Time-course of iodine elimination by hemodialysis in patients with renal failure after angiography. Author(s): Department of Medicine, Division of Nephrology and Dialysis, Social Insurance Chuo General Hospital, Tokyo, Japan. [email protected] Source: Shinoda, T Hata, T Nakajima, K Yoshimoto, H Niwa, A Ther-Apher. 2002 December; 6(6): 437-42 1091-6660

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Use of vitamin D analogs in chronic renal failure. Author(s): Division of Nephrology, Department of Medicine, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, IL 60201, USA. Source: Kim, G Sprague, S M Adv-Ren-Replace-Ther. 2002 July; 9(3): 175-83 1073-4449

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to renal failure; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Niacin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,892,00.html

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Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com •

Minerals Biotin Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Calcium Acetate Source: Healthnotes, Inc.; www.healthnotes.com Chromium Source: Healthnotes, Inc.; www.healthnotes.com Chromium Source: Prima Communications, Inc.www.personalhealthzone.com Chromium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10018,00.html Naproxen/Naproxen Sodium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com

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Potassium Chloride Source: Healthnotes, Inc.; www.healthnotes.com Vitamin H (Biotin) Source: Integrative Medicine Communications; www.drkoop.com •

Food and Diet Diabetes Source: Healthnotes, Inc.; www.healthnotes.com The Zone Diet Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. DISSERTATIONS ON RENAL FAILURE Overview In this chapter, we will give you a bibliography on recent dissertations relating to renal failure. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “renal failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on renal failure, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Renal Failure ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to renal failure. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Acute Renal Failure Following Nonmyeloablative Hematopoietic Cell Transplantation by Parikh, Chirag Rohit; PhD from University of Colorado Health Sciences Center, 2003, 99 pages http://wwwlib.umi.com/dissertations/fullcit/3086280

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Acute Renal Failure: Cost-effectiveness Analysis and Expert Probability Predictions of Prevention and Treatment Strategies by Durtschi, Amy Jean; PhD from The Ohio State University, 2003, 254 pages http://wwwlib.umi.com/dissertations/fullcit/3093643

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Chronic Renal Failure: a Study of Death Anxiety in Dialysis and Kidney Transplant Patients by Blakely, Karen B; PhD from The University of Manitoba (Canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK35825

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Chronic Renal Failure and School Performance: The Effects of Kidney Function on Academic Achievement by Steil, Dennis Alan, PhD from The University of Iowa, 1985, 77 pages http://wwwlib.umi.com/dissertations/fullcit/8611145

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Diphenylhydantoin-Protein Binding in Chronic Renal Failure by Kinniburgh, David William; PhD from University of Calgary (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK52397

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Effect of Chronic Renal Failure on Cytochrome P450 Catalytic Activities by Rege, Bhaskar Mahesh; PhD from Virginia Commonwealth University, 2003, 259 pages http://wwwlib.umi.com/dissertations/fullcit/3082012

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Micropuncture Studies on the Remnant Kidney of a Dog: a Model of Chronic Renal Failure by Wong, Norman Lok Man; PhD from McGill University (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK14595

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Renal Failure: a Sociocultural Investigation of an Illness by Faber, Shawna Marie; PhD from The University of British Columbia (Canada), 1999, 231 pages http://wwwlib.umi.com/dissertations/fullcit/NQ46342

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Renal Hemodynamic Studies in Acute Renal Failure by Fung, Henry Yiu-Ming; PhD from The University of Manitoba (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK11471

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Selective Alterations of Cadherin/Catenin Complexes during Mercuric ChlorideInduced Acute Renal Failure Are Related to the Spatial Pattern of Expression in Mouse Kidney by Jiang, Jing; PhD from Texas A&M University, 2003, 90 pages http://wwwlib.umi.com/dissertations/fullcit/3088151

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The Process of Adjustment in Chronic Renal Failure and Hemodialysis by Blodgett, Christopher Jay; PhD from The University of Manitoba (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK54475

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Use of Isolated Perfusion System in the Study of Noradrenaline-induced Acute Renal Failure in the Dog by Strand, Linda Margaret; PhD from The University of Manitoba (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK47244

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 4. CLINICAL TRIALS AND RENAL FAILURE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning renal failure.

Recent Trials on Renal Failure The following is a list of recent trials dedicated to renal failure.8 Further information on a trial is available at the Web site indicated. •

A clinical study to assess the safety of PEG-hirudin (SPP200) compared to heparin in patients who are on haemodialysis Condition(s): Chronic Kidney Failure; Vascular Graft Occlusion Study Status: This study is currently recruiting patients. Sponsor(s): Speedel Bio; Quintiles Purpose - Excerpt: The study will look at the safety profile (unwanted effects) of the long-lasting anticoagulant PEG-hirudin (SPP200) and compare these unwanted effects to those of unfractionated heparin, commonly used in haemodialysis to avoid clotting of the graft and of the haemodialysis machine. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074620

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Combined Bone Marrow and Kidney Transplant for Multiple Myeloma with Kidney Failure Condition(s): Kidney Failure, Chronic; Multiple Myeloma Study Status: This study is currently recruiting patients.

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These are listed at www.ClinicalTrials.gov.

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Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance Network Purpose - Excerpt: The purpose of this study is to determine whether a combined bone marrow and kidney transplant will be effective in treating stage II or greater multiple myeloma and associated kidney failure. This study will determine whether transplant rejection and the need for immunosuppressive drugs are decreased with this combined transplant approach. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062621 •

Comparison of daily nocturnal hemodialysis with daily hemodialysis Condition(s): Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Hemodialysis remains associated with a high mortality (approximately 22% per year) and many complications despite improvements over the last twenty years. Several nephrologists have suggested that increasing the frequency and amount of dialysis will result in improved outcomes. In fact, various forms of daily dialysis have been performed in over 300 patients in the last 30 years with improvements in blood pressure, quality-of-life, bone disease, and other complications of renal failure. Whether this form of treatment can be expanded to the 220,000 Americans on hemodialysis is unknown. The primary outcome of this study is to determine the effectiveness of nocturnal dialysis in hemodialysis patients in St. Louis. If the pilot study is effective, then participation in a larger, multicenter trial is expected. The endpoints measured are use of antihypertension medications, improvement in secondary hyperparathyroidism and use of phosphorus binders, quality-of-life measured by SF-36 surveys, and improvement in physical function as measured by maximal oxygen uptake. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012441

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Patient-Provider Trust Among Individuals with End-Stage Kidney Disease Condition(s): Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will examine communication and trust between patients in the kidney transplant process and their health care providers. It will assess patients' perception of trust in their physician and nurse coordinator; determine the patients' level of trust in the areas of competence, compassion, control, communication, and confidentiality; and determine how the trust level varies as patients progress in the transplant process. Patients 18 years of age and older who are in various stages of the kidney transplant process at Walter Reed Army Medical Center and the NIH Clinical

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Center may be eligible for this study. Candidates include individuals who: -are on dialysis but not on a transplant waiting list -are on the organ waiting list and are also on dialysis -are on the organ waiting list but are not on dialysis -have had a kidney transplant within the last year. Participants will be interviewed by someone who is not their direct health care provider about the doctor/patient, primary provider/patient, or nurse/patient relationship, their health history, medical condition, and ideas about their care. With the patient's permission, parts of the interview will be tape-recorded. The interview will take about 30 to 40 minutes. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00075036 •

Phase I Study of Alpha-Melanocyte Stimulating Hormone in Patients with Acute Renal Failure Condition(s): Acute Renal Failure Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; University of Texas Purpose - Excerpt: Objectives: I. Determine the maximum tolerated dose and safety of alpha-melanocyte stimulating hormone (alpha-MSH) in patients with acute renal failure. II. Determine the safety and pharmacokinetics of alpha-MSH in patients at high risk of acute renal failure after renal transplantation. III. Determine the safety and pharmacokinetics of alpha-MSH in patients with established ischemic acute renal failure. IV. Determine the effect of alpha-MSH on interleukin-10 pharmacokinetics. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004496

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Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis) Condition(s): Fibrosis; Focal Glomerulosclerosis; Kidney Failure; Nephrotic Syndrome; Proteinuria Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will examine the effectiveness of the drug pirfenidone in treating focal segmental glomerulosclerosis (FSGS). Patients with this disease have kidney fibrosis (scarring) and proteinuria (excessive excretion of protein in the urine). About half of patients with FSGS eventually require kidney dialysis or transplant. Steroids, which are currently used to treat the disease, are effective in only a minority of patients. Other drugs, such as cyclosporin and cyclophosphamide, improve proteinuria in a very small percentage of patients and have serious side effects. Patients with FSGS who wish to participate in this study will undergo pre-study evaluation with blood and urine tests. Patients must be on a stable dose of an ACE inhibitor (a drug that lowers blood pressure and reduces proteinuria) for at list 6 months before starting pirfenidone therapy. (Patients who are not already taking an ACE inhibitor will be started on the drug; those who cannot tolerate ACE inhibitors will be given a different drug.) Patients with elevated cholesterol will take a cholesterol-lowering drug. A diet containing

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approximately 1 gram of protein per kilogram of body weight per day will be recommended. Patients will take pirfenidone by mouth 3 times a day for 12 months. Blood and urine will be tested once a month, either at NIH or by the patient's local kidney specialist. They will collect two 24-hour urine samples at the beginning of the treatment period, at 2-month intervals throughout the study, and at a 6-month followup. Patients will also be asked to give three to five tubes of blood and urine samples for analysis during the study. In animal studies, pirfenidone improved kidney function and proteinuria and reduced kidney scarring in rats with a disease similar to FSGS. In human studies, pirfenidone improved breathing and survival in patients with lung fibrosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001959 •

Prospective Controlled Study of Posttransplant Diabetes Condition(s): Diabetes Mellitus; Kidney Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Research participants will be asked to undergo complete medical history, physical examination and blood tests. The purpose of these tests is to determine whether persons are predisposed to develop diabetes mellitus after kidney transplantation and also to make an early diagnosis if a patient develops diabetes mellitus. Medical information collected as part of the standard transplant evaluation and posttransplant medical care may be incorporated into this study. It is important to realize that research subjects will not be given an experimental drug as part of this study. After kidney transplantation, research subjects will be followed in the posttransplant clinic visits. The study will last up to 6 months. During this time the subjects may be asked to participate in clinical assessment visits (medical history and physical examination), and also during the third or fourth month after transplant will be asked to do a repeat glucose tolerance test. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006331

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Randomized Study of Recombinant Human Growth Hormone in Patients on Chronic Hemodialysis or Peritoneal Dialysis Condition(s): Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Vanderbilt University Medical Center Purpose - Excerpt: Objectives: I. Assess the clinical safety and long term effects of recombinant human growth hormone on a defined range of nutritional indices in malnourished chronic hemodialysis and continuous ambulatory peritoneal dialysis patients.

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004429 •

Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant Condition(s): Kidney Failure; Bone Marrow Transplantation; Kidney Transplantation; Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance Network Purpose - Excerpt: This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063817

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Renal Study Condition(s): Acute Renal Failure Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: ATN is a multi-center, prospective, randomized, parallel-group trial of an intensive strategy versus conventional strategy of renal replacement therapy for the treatment of acute renal failure (ARF) secondary to acute tubular necrosis in critically ill patients. The primary hypothesis is that the intensive strategy will reduce 60-day all cause mortality by 10% compared to the conventional strategy - i.e., a reduction from 55% in the conventional arm to 45% in the intensive arm. Secondary outcomes are 60-day in-hospital all-cause mortality, 1-year all cause mortality, and recovery of renal function by day 28. The study will recruit 1164 patients over a period of 3 years and each patient will be actively followed for 60 days. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00076219

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Resistance Training and Diet in Patients with Chronic Renal Failure Condition(s): Kidney Failure, Chronic

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Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study will examine the effects of long-term adherence to a low protein diet (LPD) of 0.6 g/kg-1/d-1 with and without progressive resistance exercise training in patients with impaired renal function on body composition, renal function (glomerular filtration rate), nitrogen balance, muscle strength and size, and functional capacity. The hypothesis is that adherence to a LPD will result in a reduction in skeletal muscle mass and reduced strength and functional capacity while those patients who adhere to the LPD and exercise will demonstrate a similar preservation of renal function but will have greater fat free mass, muscle mass and strength. The intervention trial will last 18 months in which patients with moderate renal failure will be randomly assigned to one of 4 interventions: standard care, standard care + exercise, LPD, and LPD with exercise. In this way the independent and combined effects of diet and exercise on the progression of renal disease and body composition will be monitored. This study will have important implications for the treatment of patients with chronic renal failure. New strategies of combining exercise with recommendations of a low protein diet may slow the progression of renal disease and improve strength and functional capacity in these at-risk patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018317 •

Screening for Patients Needing Kidney, Kidney-Pancreas, or Islet-Cell Transplant Condition(s): Diabetes Mellitus; Kidney Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Kidney transplantation is the preferred treatment for most end-stage kidney disease. This procedure is limited, however, by two major factors: 1) a shortage of donor organs and 2) organ rejection by the recipient. The National Institute of Diabetes and Digestive and Kidney Diseases is screening patients with kidney failure or diabetes who may be eligible for kidney, kidney and pancreas, or islet cell transplantation. Patients in this screening study are not offered treatment. When the screening is complete, patients will be offered an opportunity to participate in another institute study, or, if there are no active studies appropriate for the patient, other options will be suggested to the primary or referring physician. Patients found eligible for a study are not obligated to participate. Screening for all patients typically consists of blood tests, urinalysis, electrocardiogram, PPD tuberculosis screen and pregnancy test. Chest and kidney X-rays and other studies may be done on patients determined eligible for a particular study, including transplantation. A summary of all test results will be sent to the referring physician unless the patient requests otherwise. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001859

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Search for New Methods to Detect Acute Renal Failure Condition(s): Kidney Failure

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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The purpose of this study is to find substances in the blood and urine that indicate that a person has kidney damage. It will identify proteins found only in patients with acute kidney failure but not in normal healthy people or in patients with volume depletion. Adults and children who are at least 3 years old who fall into one of the following four categories may be eligible for this study: 1. Are healthy and have normal kidney function 2. Have volume depletion (this condition differs from acute kidney failure in that it is easily treated with fluids) 3. Are at high risk of kidney failure 4. Have acute kidney failure (kidney shutdown) All study participants will have a history and physical examination. Up to four blood samples of 3 tablespoons each will be taken for laboratory analysis. Urine will be collected for analysis and to measure urine output. The participants' length of stay in the study varies. People with normal kidney function will be in the study for 1 day and patients with volume depletion will be studied 3 days. The length of hospitalization of patients at high risk of kidney failure or in acute kidney failure will depend on the patient's condition and medication requirements. The results of this study may lead to the development of earlier and more accurate methods for diagnosing acute kidney failure. With earlier detection, treatment could be started earlier, possibly preventing further damage and helping recovery of injury that has already occurred. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026702 •

Study to evaluate the effectiveness of StaphVAX in adults on hemodialysis Condition(s): Staphylococcal Infections; Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): Nabi Biopharmaceuticals Purpose - Excerpt: Two part study testing the effectiveness and safety of StaphVAX vaccine in chronic hemodialysis patients against infection by Staphylococcus aureus Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071214

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Vascular Access Clinical Trials Data Coordinating Center Condition(s): Kidney Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Cleveland Clinic Foundation Hospital; Boston University School of Medicine; Duke University; University of Iowa; Maine Medical Center; University of Texas; University of Alabama, Birmingham; Washington University School of Medicine Purpose - Excerpt: Fistula Study: The objective of the study is to determine whether clopidogrel reduces the early failure rate of native AV fistulae. Graft Study: The

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objective of the study is to determine whether Aggrenox (Boehringer-Ingelheim) prolongs primary unassisted patency in newly created arteriovenous grafts. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067119 •

Cardiac and Renal Disease Study (CARDS) Condition(s): Coronary Disease; Cardiovascular Diseases; Cerebrovascular Accident; Heart Failure; Heart Diseases; Peripheral Vascular Diseases; Diabetes Mellitus; Hypertension; Kidney Failure, Chronic Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the epidemiology of renal disease and its relationship to cardiovascular disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049907

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Homocysteine Study (HOST) Condition(s): Renal Failure; End Stage Renal Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; Pan American Laboratories; Abbott Laboratories Purpose - Excerpt: The primary objective of this study is to test the hypothesis that administration of folate, pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) in high doses to patients with advanced chronic renal failure or end stage renal disease and abnormally high plasma homocysteine levels will lower the homocysteine levels and the death rate compared to patients who receive placebo. The secondary objective is to test the hypothesis that intake of the vitamins compared to placebo decreases the incidence of myocardial infarction, disabling stroke, and amputation of a lower extremity and, in hemodialysis patients, thrombosis of the vascular access. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032435

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Risk Factors for CV Disease in a Dialysis Cohort Condition(s): Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Kidney Failure, Chronic Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)

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Purpose - Excerpt: To investigate whether traditional risk factors and novel risk factors predict higher risk of atherosclerotic cardiovascular disease (ASCVD) in a prospective study of incident dialysis patients. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006297 •

Sirolimus and Thymoglobulin to Prevent Kidney Transplant Rejection Condition(s): Kidney Failure Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will test the safety and effectiveness of two drugs, Sirolimus and Thymoglobulin, for preventing rejection of transplanted kidneys. Standard anti-rejection therapy uses a combination of drugs, such as cyclosporine, tacrolimus, azathioprine, steroids, and others, that are taken daily for life. However, even with this daily therapy, more than half of kidney recipients slowly reject their transplant within 10 years. Both Thymoglobulin, an antibody, and Sirolimus, an antirejection drug, prevent rejection by lowering the response of the immune system to the transplanted organ. Thymoglobulin is given in the pre- and postoperative period, and Sirolimus is taken long term. Patients who receive a kidney transplant at the National Institutes of Health Clinical Center are eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests. Participants will undergo a kidney transplant. Before the surgery, a central line (intravenous catheter), through which blood and medicine can be given, is placed in the neck or chest. Patients may also undergo leukapheresis, a procedure for collecting white blood cells. The cells can be stored for transfusion later if white cell counts drop following Thymoglobulin treatment. For this procedure, blood is drawn from a needle placed in the arm and flows into a machine that separates the blood components by spinning. The white cells are collected in a bag and the red cells and plasma are returned through a second needle in the other arm. Thymoglobulin will be given intravenously the day before the transplant and days 1 through 9 after the operation. Sirolimus will be taken by mouth, mixed with water or orange juice. Sirolimus therapy starts the day of the transplant and continues for life. Follow-up study visits will be scheduled weekly for the first month after the transplant, then every 6 months for 1 year and then once a year for 4 years. Procedures during these visits may include blood and urine tests, physical examination, and check of vital signs (i.e., blood pressure, heart rate, breathing rate, temperature). Kidney biopsies (removal of a small piece of tissue for examination under the microscope) will be done at 2 weeks, 1 month and 6 months after surgery and then yearly for 4 years to check for any damage to the kidney. In addition, a local doctor will do routine laboratory tests 2 to 3 times a week for the first 2 to 3 months after transplantation, then weekly for several additional months, and at least monthly for life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006178

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Fifteen Year Follow-up of 5,500 Black and 5,500 Other Hypertensives Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Kidney Failure, Chronic Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To seek predictors of mortality, hospitalization, and dialysis using data from a hypertensive population which began treatment in 1974. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005417

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Genetic Analysis of Human Hypertensive End Stage Renal Disease (H-ESRD) Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Kidney Failure, Chronic Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To identify genes causing hypertensive end-stage renal disease (HESRD) in high risk African-American populations Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005536

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Imatinib Mesylate in Treating Patients With Advanced Cancer and Kidney Failure Condition(s): adult solid tumor; central nervous system cancer; Gastrointestinal Cancer; hematopoietic and lymphoid cancer Study Status: This study is completed. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by stopping the enzyme necessary for cancer cell growth. Kidney failure may delay the elimination of imatinib mesylate from the body, which may lead to longer drug exposure and increase toxic side effects. PURPOSE: Phase I trial to determine the dose of imatinib mesylate that is most effective with the least amount of toxic side effects in treating patients who have advanced cancer and kidney failure. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026169

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Isoflavones and Acute-phase Response in Chronic Renal Failure Condition(s): Kidney Failure, Chronic Study Status: This study is completed. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM)

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Purpose - Excerpt: This is a randomized, double-blinded dietary intervention in hemodialysis patients to determine the clinical and metabolic effects of soy isoflavones on disease activity, including improvement of blood markers of acute-phase response, and decreased blood levels of markers of metabolic bone disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029796 •

Kidney Transplant for HIV-Infected Patients in Renal Failure Condition(s): Chronic Kidney Failure; HIV Infection Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will examine the safety and effectiveness of renal (kidney) transplantation for HIV-infected patients with end-stage renal disease (kidney failure). Although kidney transplant is the best treatment for most causes of kidney failure, people infected with HIV are not offered this procedure because the immunosuppressive drugs (drugs that suppress immune function) required to prevent organ rejection could further impair the patient's already weakened immune system. This study will use a regimen of immunosuppressants designed to complement treatment for patients taking highly active antiretroviral therapy (HAART). HIVinfected patients between 18 and 60 years of age with renal failure who have not had any opportunistic infections for 5 years may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests. Before the transplant procedure, participants will undergo additional tests and procedures, including blood studies, 24-hour urine collection, infectious disease consultation, tuberculin skin test, PAP smear for women, chest X-ray, brain and hip MRI studies and DEXA-scan to evaluate bone density. In addition, patients may undergo leukapheresis to obtain white blood cells for study. For this procedure, whole blood is drawn through a needle in an arm vein and passed through a cell separator machine. The white cells are collected for removal, and the rest of the blood is returned to the body through the same needle or another needle in the other arm. When a donor organ becomes available for transplant, the patient will receive three anti-rejection drugs-cyclosporine, mycophenolate mofetil and prednisone-to prevent organ rejection. Immediately after the surgery, HAART drugs will be stopped for 7 days until stable levels of the immune suppressants can be achieved. Then, HAART will be re-started and all medications will be adjusted to achieve adequate blood levels. Patients must stay in the local area 60 days after discharge from the hospital for monitoring. Frequent blood samples will be taken to monitor kidney function, viral load and CD4+ T cell counts. Follow-up visits will then be scheduled monthly for the first 6 months after transplant, then every other month for 1 year. Kidney biopsies will be done at the end of the first month, after 6 months, and yearly for 5 years. For the biopsy, a special needle is used to remove a small piece of kidney tissue for microscopic examination. The biopsies and blood tests are done to evaluate the immune response to the transplanted organ and to study how HAART interacts with the immune suppressing drugs. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00009009 •

Oxidative Stress in Chronic Kidney Disease Condition(s): Cardiovascular Diseases; Heart Diseases; Kidney Failure, Chronic Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine how the progressive loss of kidney function influences cardiovascular disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069810

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Parathyroid hormone levels in relation to the phosphorus content of meals Condition(s): Renal Failure Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Patients on hemodialysis tend to have chronic elevations in the level of phosphorus in the blood and a secondary increase in the iPTH level. This chronic elevation in iPTH can have adverse consequences, thus a variety of phosphate binders are given in an attempt to decrease the absorption of phosphorus present in the normal diet. Some preliminary studies have indicated that the iPTH level may change based on the amount of phosphorus present in a meal prior to any significant absorption of phosphorus. If this is true in hemodialysis patients, then the timing of the administration of phosphate binders in relation to the ingestion of meals needs to be considered Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018135

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Pharmacokinetics/Pharmacodynamics of Argatroban Injection in End-Stage Renal Disease Patients Undergoing Hemodialysis Condition(s): Kidney Failure, Chronic; Renal Disease, End-Stage Study Status: This study is completed. Sponsor(s): Texas Biotechnology Corporation Purpose - Excerpt: The primary goals of this investigation are to provide guidance on how to dose Argatroban in patients undergoing hemodialysis and to assess the safety and tolerability of Argatroban in hemodialysis patients. The secondary goal of the study will be to assess the adequacy of anticoagulation during hemodialysis. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035178

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Phase 1 Study of Imatinab (STI571) in Patients with Advanced Cancer and Kidney Dysfunction Condition(s): Neoplasm; Kidney Failure Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine a safe dose of imatinab (also known as STI571 and Gleevec) for cancer patients whose kidneys are not working normally. The kidney helps eliminate drugs from the body. Patients with abnormal kidney function may require lower doses of some drugs or may not be able to use others at all. Imatinab is approved for patients with chronic myeloid leukemia and has shown activity against other leukemias and stomach and intestinal tumors. Its effect in other cancers is not known. Patients 18 years of age and older with any type of advanced cancer that cannot be treated successfully with surgery or other standard therapies may be eligible for this study. Patients with mild, moderate or severe kidney dysfunction may participate. Candidates will be screened with imaging studies, such as X-rays, CT or MRI scans, and blood tests. Women of childbearing potential will have a pregnancy test. Pregnant women may not participate in the study. Participants will take imatinab by mouth on day 1 of the study followed by a 2-day break to see how long the drug stays in the body. From day 4 on, patients will take imatinab once a day. A 24-hour urine sample will be collected on day 1, and blood samples will be drawn on days 1, 2, 3 and 4. On day 1, blood will be drawn just before the drug is administered, then at 7 time points after the drug is given. Two samples will be drawn on day 2 and one sample on the mornings of days 3 and 4. A total of about 7 tablespoons of blood will be drawn over the 4 days. Blood sampling will be repeated on days 15 and 16. Participants will be hospitalized the first few days of the study and overnight on day 15 to allow for the blood draws and evaluation. The initial drug dose will be increased gradually in succeeding groups of patients until the highest safe dose is determined. An individual's dose may be raised or lowered depending on side effects. In addition to the blood and urine tests described above, patients will have the following procedures to evaluate drug side effects and the response to treatment: - Physical examinations. - X-rays, CT, MRI or other scans (about every 8 weeks) to check the status of the cancer. - Blood draws for routine tests and to check blood cell counts and liver and kidney function. Patients will keep a record of the type and duration of drug side effects they experience. Treatment will continue as long as the side effects are tolerable and the tumor shrinks or remains stable in size. Treatment will be stopped if the tumor grows, if side effects are too severe, or if the patient chooses to stop. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028392

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Retrovir Capsules in the Treatment of HIV-Infected Patients in Renal Failure Condition(s): HIV Infections; Kidney Failure, Chronic Study Status: This study is completed. Sponsor(s): Glaxo Wellcome

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Purpose - Excerpt: To evaluate the safety, tolerance, and pharmacokinetics of Retrovir (AZT) administration in HIV-infected patients in renal failure receiving maintenance hemodialysis. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002047 •

Study to Evaluate the Effects of Zemplar Injection and Calcijex on Intestinal Absorption of Calcium Condition(s): Hypoparathyroidism; Hypercalcemia; Kidney Failure, Chronic Study Status: This study is not yet open for patient recruitment. Sponsor(s): Abbott Laboratories Purpose - Excerpt: A study to investigate the effects of Zemplar and Calcijex on intestinal calcium absorption in hemodialysis subjects Phase(s): Phase IV Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00073710

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “renal failure” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON RENAL FAILURE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “renal failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on renal failure, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Renal Failure By performing a patent search focusing on renal failure, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on renal failure: •

Adenoviral vectors encoding erythropoietin and their use in gene therapy Inventor(s): Ciliberto; Gennaro (Pomezia, IT), La Monica; Nicola (Pomezia, IT), Savino; Rocco (Pomezia, IT) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 6,641,807 Date filed: April 23, 2001 Abstract: Helper dependent adenoviral vectors encoding erythropoietin (epo) provide high levels of epo to achieve a long-term therapeutically effective dosage, and allow for repeat administration to patients with disorders such as anaemia of Chronic Renal Failure (CFR), anaemias due to beta-thalassaemia, and sickle cell anaemia (SCA). Excerpt(s): The present invention relates to the delivery of erythropoietin (EPO) to a mammal. More particularly, the present invention relates to provision of EPO in a mammal by means of expression from encoding nucleic acid included in an expression vector, that is by means of gene therapy. The present invention is based on the inventors' experimental demonstration that therapeutic levels of EPO can be achieved using helper-dependent adenoviral (Hd-Ad) vectors, which levels are far beyond any levels previously attained using a variety of vectors, including adenoviral (Ad) vectors (i.e. non-helper-dependent). Erythropoietin (EPO) is a protein of great interest because of its therapeutic usefulness in a variety of diseases. As is well known, the gene for human EPO was cloned by Amgen (see e.g. WO85/02610, EP-A-0148605) and recombinantly produced EPO (rEPO) has attained a huge market (in excess of 2.9 billion dollars). Currently, rEPO is administered to patients in protein form. Despite its success, there is a number of problems with delivery of rEPO resulting in various unmet clinical needs, primarily because of the prohibitive cost of providing sufficient rEPO to achieve a long-term therapeutically effective dosage. Sufferers include individuals with anaemia of Chronic Renal Failure (CRF), anaemias due to beta-thalassaemia, and sickle cell anaemia (SCA). Large numbers of such individuals go untreated despite the fact that good therapeutic results can be achieved as long as enough EPO is provided. Web site: http://www.delphion.com/details?pn=US06641807__

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Bioenhanced formulations comprising eprosartan in oral solid dosage form Inventor(s): Gudipati; Manga R. (Hatfield, PA), Venkatesh; Gopadi M. (Troy, MI) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,517,871 Date filed: May 23, 2001 Abstract: This invention relates to bioenhanced formulations comprising eprosartan or eprosartan mesylate in the amorphous form, a process for its production, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to a phamaceutically active compound, bioenhanced formulations of eprosartan or eprosartan mesylate, processes for manufacturing the

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compound and these formulations and methods of using the bioenhanced formulations of eprosartan in the treatment of certain disease states in mammals, in particular man. Most specifically, the present invention relates to the use of eprosartan or eprosartan mesylate in the production of bioenhanced immediate and modified (both sustained and targeted) release oral solid dosage forms (tablet or capsule formulations) to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1Himidazol-5-yl]methyl ene-2-thiophenepropionic acid is known by the name eprosartan and is the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyle ne-2-thiophenepropionic acid and its methanesulfonate salt (eprosartan mesylate). Additionally, the '351 patent discloses conventional techniques for formulating (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. Because the variable and mean absolute bioavailability of eprosartan is approximately 13%, doses as high as 800 mg per day may be required for an effective treatment of hypertension, congestive heart failure and renal failure. Additionally, since the commercial form of the drug is as its mesylate, which becomes dihydrated during the formulation process, high dose tablets (e.g., 600 mg tablets weigh 1,200.0 mg) may be difficult to swallow. Therefore, there is a need for a formualtion that enhances the bioavailabiltiy of eprosartan. Web site: http://www.delphion.com/details?pn=US06517871__ •

CRFG-1b, a target and marker for chronic renal failure Inventor(s): Laping; Nicholas J (West Chester, PA), Olson; Barbara (Norristown, PA), Zhu; Yuan (Blue Bell, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,255,471 Date filed: February 9, 1998 Abstract: CRFG-1b polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing CRFG-1b polypeptides and polynucleotides in the design of protocols for the treatment of chronic renal disease, renal ischemia, diabetic nephropathy, acute renal failure, neurodegenerative disease, and Alzheimer's disease, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to GTP binding protein family, hereinafter referred to as chronic renal failure gene-1b (CRFG-1b). The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. The sequence of CRFG-1b is similar to uncharacterized putative GTP binding proteins of yeast (YPL093w), Halobacterium cutirubrum and GTP1/OBG family of GTP binding proteins from Methanobacterium thermoautotrophicum. GTP binding proteins play important roles in intracellular transport, protein targeting and vesicle fusion. This indicates that the GTP binding proteins fainly has an established, proven history as therapeutic targets. Clearly there is

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a need for identification and characterization of fiuter members of GTP binding protein family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, chronic renal disease, renal ischemia, diabetic nephropathy, acute renal failure, Neurodegenerative disease, and Alzheimer's disease. Web site: http://www.delphion.com/details?pn=US06255471__ •

Cytokine suppressive anti-inflammatory drug binding protein Inventor(s): Kumar; Sanjay (King of Prussia, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,350,856 Date filed: March 24, 1998 Abstract: p38beta2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing p38beta2 polypeptides and polynucleotides in the design of protocols for the treatment of central nervous system disorder such as senile dementia of the Alzheimer's type (SDAT), multiple sclerosis, cerebral malaria, stroke, head trauma and spinal cord injury; cardiovascular diseases such as restenosis and atherosclerosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma; and other such diseases or conditions associated with dysregulated or excess cytokines such as osteporosis, sepsis due to surgical or traumatic incident, chronic renal failure, AIDs, cachexia and autoimmune conditions such as lupus erthyromatosis, host graft rejection and graft versus host disease, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to CSBP/p38 MAP Kinases family, hereinafter referred to as p38beta2. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. Cytokines play an important role in regulating the cellular response during inflammation and other immune functions. Of particular interest are the cytokines interleukin-1 (IL-1,.alpha. and.beta.) and tumor necrosis factor (TNF,.alpha. and.beta.), which are the intercellular proteins involved in the initial step of the inflammatory response cascade (Arai, et al., Ann. Rev. Biochem. 59: 783-836 (1990). Thus, there has been a substantial amount of research recently devoted to interfering with the production of IL-1 and TNR in response to an inflammatory stimulus. One therapeutic approach involves suppressing the production of IL-1 and TNF at the level of transcription and/or translation and/or secretion. The activities associated with certain of pyridinyl imidazoles led to a class of compounds referred to as "CSAIDs", or Cytokine Suppressing Anti-Inflammatory Drugs. These compounds appear to arrest the expression of IL-1 and TNF predominantly at the translational level, although a lesser effect on transcription has also been observed but effects on other steps cannot be ruled out. Web site: http://www.delphion.com/details?pn=US06350856__

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Eprosartan dihydate and a process for its production and formulation Inventor(s): Duddu; Sarma (Redwood City, CA), Palepu; Nageswara R. (Northwood, GB), Venkatesh; Gopadi M. (King of Prussia, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,420,412 Date filed: March 15, 2001 Abstract: The invention relates to (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methy lene-2-thiopheneproprionic acid monomethanesulfonate dihydrate, a process for its production, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to a pharmaceutically active compound, a process for its production, compositions containing the compound and methods of using the compound in the treatment of certain disease states in mammals, in particular man. More specifically, the present invention relates to (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate dihydrate, a wet granulation process for preparing said compound, compositions containing this compound, and methods of using (E)-.alpha.[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2thiophenepropionic acid monomethanesulfonate dihydrate to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate is known by the name "eprosartan" and is the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses in Example 41 a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2thiophenepropionic acid monomethanesulfonate. Additionally, the '351 patent discloses conventional techniques for formulating (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate and Examples 108-111 specifically detail the preparation of certain formulations. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. Surprisingly, it has been found that the dihydrated form of (E)-.alpha.-[2n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2thiophenepropionic acid monomethanesulfonate is formed in situ during the wet granulation process for preparing solid dosage forms of the anhydrous form of said compound. Additionally, it has been found that the dihydrate of eprosartan is obtained by recrysallizing the anhydrouus form from an aqueous acidic solution. The dihydrate has the improved property of being more compactible in the solid dosage form when compared to the corresponding anhydrous form of the compound. This is particularly important when formulating (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)-methyl]-1Himidazol-5-yl]methy lene-2-thiophenepropionic acid monomethane-sulfonate for therapeutic use. Web site: http://www.delphion.com/details?pn=US06420412__

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Eprosartan monohydrate Inventor(s): Duddu; Sarma (Foster City, CA), Palepu; Nageswara R (Northwood, GB), Venkatesh; Gopadi M (King of Prussia, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,262,102 Date filed: December 8, 1999 Abstract: This invention relates to (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1) H-imidazol-5-yl]methylene-2-thiophenepropionic acid monomethanfesulfonate monohydrate, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to a pharmaceutically active compound, compositions containing the compound and methods of using the compound in the treatment of certain disease states in mammals, in particular man. More specifically, the present invention relates to (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate monohydrate, compositions containing this compound, and methods of using (E)-.alpha.-[2-n-butyl-1[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate monohydrate to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound (E)-.alpha.-[2-nbutyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate is known by the name "eprosartan" and is the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses in Example 41 a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate. Additionally, the '351 patent discloses conventional techniques for formulating (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate and Example; 108-111 specifically detail the preparation of certain formulations. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. It has been found that the monohydrate of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate is formed during the vacuum drying of the dihydrated form of this compound or when the anhydrate of (E).alpha.-[2-n-butyl-1-[(4-carboxy-phenyl)methyl]-1H-imidazol-5-yl]methy lene-2thiophenepropionic acid monomethanesulfonate is granulated with water, stored at 50.degree. C. overnight and vacuum dried overnight at ambient temperature. Web site: http://www.delphion.com/details?pn=US06262102__

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HAS2 splicing variant HOEFC11: a target in chronic renal failure, inflammatory diseases and myocardial ischemia Inventor(s): Nambi; Ponnal (Berwyn, PA), Pullen; Mark A (Colmar, PA), Zhu; Yuan (Blue Bell, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,350,446 Date filed: August 30, 1999

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Abstract: HOEFC11 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HOEFC11 polypeptides and polynucleotides in the design of protocols for the treatment of chronic renal failure, inflammatory diseases, myocardial ischemia, cancer, rheumatoid arthritis, cirrhotic liver disease, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to the hyaluronan synthase family, hereinafter referred to as HOEFC11. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. Hyaluronic acid (HA), an important constituent of extracellular matrix, is a linear polysaccharide of alternating glucuronic acid and N-acetyl glucosamine residues. It is synthesized by a membrane-bound enzyme hyaluronan synthase (HAS) and extruded into the extracellular space. Cloning of two human HAS (HAS 1 and HAS 2) has been reported very recently (K. Watanabe and Y. Yamaguchi, J. Biol. Chem. 271:22945-22948, 1996) (N. Itano and K. Kimata, Biochem. Biophy. Res. Communications, 222:816-820, 1996). HA synthesis is involved in many cellular functions such as migration, invasion, adhesion, transformation, proliferation and wound healing. HA synthesis has been shown to be induced by FBS, PDGF, EGF, IL-1, retinoic acid, IGF, TGF beta, etc. Increased HA production is: (a) a general phenomenon in various organs attacked by inflammatory cells, (b) implicated in tissue edema, (c) a characteristic of tissue remodeling and (d) a marker for early stage of extracellular matrix remodeling following vascular injury. Increased levels of HA have been reported in chronic renal failure, inflammatory diseases, cancer (prostate, mammary and other invasive tumors), aortas from diabetic patients, smaller airways of patients with acute alveolitis, transplantation edema in rejecting heart and kidney, myocardial ischemia, balloon injury, liver cirrhosis, wound healing and angiogenesis. Hyaluronidase (breaks down HA) is reported to be beneficial in limiting cellular damage during myocardial ischemia in rat, dog and man. This indicates that the hyaluronan synthase family has a established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of further members of the hyaluronan synthase family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, chronic renal failure, inflammatory diseases, myocardial ischemia, cancer, rheumatoid arthritis, cirrhotic liver disease. In one aspect, the invention relates to HOEFC11 polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such HOEFC11 polypeptides and polynucleotides. Such uses include the treatment of chronic renal failure, inflammatory diseases, myocardial ischemia, cancer, rheumatoid arthritis, cirrhotic liver disease, among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with HOEFC11 imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate HOEFC11 activity or levels. Web site: http://www.delphion.com/details?pn=US06350446__

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High drug load immediate and modified release oral dosage formulations and processes for their manufacture Inventor(s): Venkatesh; Gopadi M. (Blue Brook, OH) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,558,699 Date filed: December 12, 2001 Abstract: This invention relates to high drug load granulation of (E)-.alpha.-[2-n-butyl-1[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid in the anhydrous form, a process for its production, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to high drug load formulations, processes for preparing these formulations, and methods of using high drug load formulations in the treatment of certain disease states in mammals, in particular man. Specifically, the present invention relates to the use of anhydrous (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid in the preparation of high drug load immediate and modified release tablet formulations, wet or dry granulation processes for preparing high drug load granules, oral dosage forms containing these high drug load granules, and methods of using high drug load formulations of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5yl]methyle ne-2-thiophenepropionic acid to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound, (E).alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyle ne-2thiophenepropionic acid, is known by the name "eprosartan" and is the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid and its methane sulfonate salt. Additionally, the '351 patent discloses conventional techniques for formulating (E).alpha.-[2-n-butyl-1-[(4-carboxyphenyl)-methyl]-1H-imidazol-5-yl]methy lene-2thiophenepropionic acid. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. International Application Number PCT/US97/04877, filed Mar. 26, 1997. relates to a novel dihydrated form of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate, in particular, in pharmaceutical compositions for the treatment of diseases in which blockade of angiotensin II receptors is indicated, for example, in the treatment of hypertension, congestive heart failure and renal failure. This form of (E).alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2thiophene-propionic acid monomethanesulfonate is produced during the wet granulation of the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methy lene-2-thiophenepropionic acid monomethanesulfonate. Web site: http://www.delphion.com/details?pn=US06558699__

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Human hypoxanthine- (guanine) phosphoribosyl transferase-2 Inventor(s): Adams; Mark D. (Potomac, MD), Bednarik; Daniel P. (Columbia, MD), Rosen; Craig A. (Laytonsville, MD) Assignee(s): Human Genome Sciences, Inc. (rockville, Md) Patent Number: 6,653,446 Date filed: November 12, 1998 Abstract: A human HPRT-2 polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for the treatment of nephrolithiasis, anemia, precocious gout, kidney stones, Lesch-Nyhan syndrome, renal failure and uricaciduria. Antagonists against such polypeptides and their use as a therapeutic to treat disorders associated with excessive purine synthesis are also disclosed. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptide of the present invention is human hypoxanthine-(guanine) phosphoribosyl transferase-2, sometimes hereinafter referred to as "HPRT-2". The invention also relates to inhibiting the action of such polypeptides. In higher animals, nucleases are secreted by the pancreas and enzymatically hydrolyze nucleic acids to yield, ultimately, the free purine and pyrimidine bases. If not salvaged and re-used, the free bases are degraded further and the end-products excreted. In some vertebrates, including the primates, the dalmatian dog, birds and some reptiles, the end-product of purine degradation is uric acid, whereas in other mammals and reptiles, and also in mollusks, the end-product is allantoin. The degradation of purines to the end-product, uric acid in man has been intensively studied, since genetic aberrations of this pathway are known. The major purines, adenine and guanine, are first converted into xanthine, which is then oxidized by the complex flavoprotein xanthine oxidase to uric acid and a superoxide radical which undergoes conversion to hydrogen peroxide by the action of superoxide dismutase. In the presence of HPRT, however, a phosphoribosyl group is added to adenine and guanine from PRPP (phosphoribosyl pyrophosphate) to form AMP or GMP with the simultaneous loss of pyrophosphate (PP.sub.i), and these may be re-used. Web site: http://www.delphion.com/details?pn=US06653446__

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Indole derivatives useful in therapy Inventor(s): Challenger; Stephen (Kent, GB), Dack; Kevin Neil (Kent, GB), Derrick; Andrew Michael (Kent, GB), Dickinson; Roger Peter (Kent, GB), Ellis; David (Kent, GB), Hajikarimian; Yousef (Kent, GB), James; Kim (Kent, GB), Rawson; David James (Kent, GB) Assignee(s): Pfizer Inc. (new York, Ny) Patent Number: 6,211,223 Date filed: April 18, 2000

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Abstract: The invention provides S-(+)-3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4methylphenyl)sulfonylami no]-2-oxoethyl}-1-methyl-1H-indole-6-carboxylic acid, which is substantially free from its (R)-(-)-enantiomer, and pharmaceutically acceptable derivatives thereof. The compounds are useful in the treatment of inter alia acute renal failure, restenosis and pulmonary hypertension. Excerpt(s): This invention relates to an indole derivative useful in the treatment of a variety of diseases including acute renal failure, restenosis, and pulmonary hypertension, and to pharmaceutical formulations containing the compound. International Patent Application WO 94/14434 discloses indole derivatives which are indicated as endothelin receptor antagonists. European Patent Application 617001 discloses a large number of phenoxyphenylacetic acid derivatives which are also indicated as endothelin receptor antagonists. Bergman et al, Tetrahedron, Vol. 31, N.degree. 17, 1975, pages 2063-2073, disclose a number of indole-3-acetic acids. Similar compounds are disclosed by Rusinova et al., Khim. Geterotsikl. Soedin., 1974, (2), 211213 (see also Chemical Abstracts, Vol. 81, N.degree. 7, Aug. 19, 1974, abstract N.degree. 37455a), and Yarovenko et al, J. Gen. Chem. USSR (English translation), Vol. 39, 1969, page 2039 (see also Beilstein, Registry Number 431619). Web site: http://www.delphion.com/details?pn=US06211223__ •

Inotropic and diuretic effects of exendin and GLP-1 Inventor(s): Beeley; Nigel R. A. (Solana Beach, CA), Prickett; Kathryn (San Diego, CA), Vine; Will (Poway, CA), Young; Andrew A. (San Diego, CA) Assignee(s): Amylin Pharmaceuticals, Inc. (san Diego, Ca) Patent Number: 6,703,359 Date filed: September 22, 2000 Abstract: Methods for increasing urine flow are disclosed, comprising administration of an effective amount of GLP-1, an exendin, or an exendin or GLP-1 agonist. Methods for increasing urinary sodium excretion and decreasing urinary potassium concentration are also disclosed. The methods are useful for treating conditions or disorders associated with toxic hypervolemia,such as renal failure, congestive heart failure, nephrotic syndrome, cirrhosis, pulmonary edema, and hypertension. The present invention also relates to methods for inducing an inotropic response comprising administration of an effective amount of GLP-1, an exendin, or an exendin or GLP-1 agonist. These methods are useful for treating conditions or disorders that can be alleviated by an increase in cardiac contractility such as congestive heart failure. Pharmaceutical compositions for use in the methods of the invention are also disclosed. Excerpt(s): The present invention relates to methods for increasing urine flow comprising administration of an effective amount of glucagon-like peptide-1[7-36] amide (abbreviated "GLP-[7-36]NH.sub.2 " or simply "GLP-1"), an exendin, or an exendin or GLP-1 agonist. Methods for increasing urinary sodium excretion and decreasing urinary potassium concentration are also disclosed. The methods are useful for treating conditions or disorders associated with toxic hypervolemia, such as renal failure, congestive heart failure, nephrotic syndrome, cirrhosis, pulmonary edema, and hypertension. Pharmaceutical compositions for use in the methods of the invention are also disclosed. The present invention also relates to methods for inducing an inotropic response comprising administration of an effective amount of an exendin, GLP-1, or an exendin or GLP-1 agonist. These methods are useful for treating conditions or disorders

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that can be alleviated by an increase in cardiac contractility, such as congestive heart failure. The following description summarizes information relevant to the present invention. It is not an admission that any of the information provided herein is prior art to the presently claimed invention, nor that any of the publications specifically or implicitly referenced are prior art to that invention. Web site: http://www.delphion.com/details?pn=US06703359__ •

Method of administration of a nutritional product to a person having renal failure Inventor(s): Lowry; Carol Jo (Minneapolis, MN), Sass; Kathy Marie (Forest Lake, MN) Assignee(s): Novartis Nutrition AG (berne, Ch) Patent Number: 6,288,116 Date filed: May 13, 1998 Abstract: L-arginine found essential to enhance the glomerular function of the kidneys is used to formulate a low viscosity, calorie-dense, nutritional product for a person having renal failure. In a product free of citric acid or citrates, for oral ingestion, the taste of arginine is counteracted by lactic, malic or adipic acid; in a formulation for tube-feeding, citric acid and citrates in a specified ratio controls the product's stability. The ratio of calcium to phosphorus is controlled, as is the caloric distribution and water content; the amounts of vitamins and minerals included provide a nutritionally complete formulation. Excerpt(s): This invention relates generally to a nutritionally complete liquid supplement (referred to as "product") for enteral feeding, which has been formulated to address the nutritional needs of persons undergoing renal dialysis because they suffer from renal failure. The product is formulated for persons who suffer from acute or chronic inflammation of kidney tissue; in particular, those who have a dysfunctional glomerulus, which is a cluster of capillaries responsible for the production of urine. It is well established that renal disease affects the nutritional status of a person with renal failure, both directly and indirectly in so many ways, that it is difficult to achieve a caloric goal by controlling the person's diet. Major factors which determine the quality of life for a patient are (a) the nutritional status of the patient when dialysis was commenced; and, (b) the patient's ability to ingest and most efficiently metabolize the nutrition provided. On the reasonable assumption that protein administration may also enhance the rate of recovery from acute renal failure, U.S. Pat. No. 5,576,287 to Zaloga et al claims a method for treating or preventing such failure by feeding the patient meat proteins but fails to teach how elemental arginine, or how much of it, can be added to improve glomerular function; or, how the calcium to phosphorus ratio can be controlled. By "elemental" arginine is meant molecular arginine (MW=174.2) which is soluble in water. Meat proteins elevate the phosphorus level and there is no indication how the calcium content is increased relative to the phosphorus to maintain a Ca/P ratio greater than 1. Calcium is malabsorbed in patients with renal disease, and they require a relatively high dietary intake; phosphorus is poorly excreted, and due to high plasma levels, phosphorus intake must be limited. A ratio greater than 1, on an elemental basis, w/w (weight for weight), helps to optimize the Ca/P balance of a renal patient undergoing dialysis. The '287 composition may also include any other nutrients including amino acids known to have specific renal vasodilator actions. Numerous considerations relating to the problems of providing a diet which will determine the availability of desirable nutrients are referred to in U.S. Pat. No. 5,108,767 to Mulchandani and need not be reiterated. Health care professionals dealing with a

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patient undergoing dialysis must cope with the need to replace the function of the kidneys. They refer to arginine as a non-essential amino acid and do not suggest providing it in elemental form. Neither the '287 nor the '767 disclosures provides the requisite motivation to prepare an acceptable renal nutritional supplement with elemental L-arginine. Web site: http://www.delphion.com/details?pn=US06288116__ •

Method of promoting erythropoiesis Inventor(s): DiZerega; Gere (Pasadena, CA), Rodgers; Kathleen E. (Long Beach, CA) Assignee(s): University of Southern California (los Angeles, Ca) Patent Number: 6,239,109 Date filed: February 8, 1999 Abstract: The present invention provides methods, compounds, pharmaceutical compositions, and kits for the augmentation of erythropoiesis by potentiating erythropoietin-induced differentiation with angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II analogues, AII fragments or analogues thereof or AII AT.sub.2 type 2 receptor agonists as a therapeutic adjunct. The method is useful for the treatment of congenital or acquired aplastic or hypoplastic anemia associated with chronic renal failure, end-stage renal disease, renal transplantation, cancer, AIDS, chemotherapy, radiotherapy, bone marrow transplantation and chronic diseases. Excerpt(s): The present invention relates to compounds, methods, compositions, and kits for the stimulation of erythropoiesis. More specifically, the present invention relates to methods, compositions, and kits that employ effective amounts of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II analogues, AII fragments or analogues thereof or AII AT.sub.2 type 2 receptor agonists for stimulating erythropoiesis. Maintenance of an adequate supply of oxygen to the body tissues is vital to survival. In the United States alone, several million people suffer from anemia secondary to renal failure, chronic inflammatory disease and malignancies (U.S. Pat. No. 4,987,121, hereby incorporated by reference in its entirety). Since to a large degree the oxygen-carrying capacity of blood is governed by the concentration of erythrocytes in the blood, the appropriate regulation of erythropoiesis is also crucial. The early studies of Reissmann (Reissmann, K. R., Blood 5:372-80 (1950)) and Erslev (Erslev, A., Blood 8:349-57 (1953)) clearly demonstrated the hypoxia-induced stimulation of erythropoietin secretion. When erythropoietin is secreted from the erythropoietinproducing cells in response to hypoxia, it travels through the blood to its target organ, the hematopoietic tissues. In humans, the principal hematopoietic tissue is within the liver before birth, and in the bone marrow after birth. (Id.) There, erythropoietin binds specifically to its receptor on the erythroid progenitor cells called burst forming uniterythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) and stimulates these cells to proliferate and differentiate (Spivak, J. L., Int. J. Cell Cloning 4:139-66 (1986)). BFU-E are the earliest erythroid progenitors and constitute 0.01%, approximately, of the nucleated bone marrow cells. CFU-E are derived from BFU-E, account for about 0.1% of marrow cells, and are much more responsive to erythropoietin than are BFU-E (Spivak, J. L., supra); Sawada, K., et al., J. Clin. Invest. 80:357-66 (1987)). Web site: http://www.delphion.com/details?pn=US06239109__

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Method of treating acute renal failure Inventor(s): Hausheer; Frederick Herman (Boerne, TX) Assignee(s): Bionumerik Pharmaceuticals, Inc. (san Antonio, Tx) Patent Number: 6,172,119 Date filed: February 9, 1999 Abstract: This invention relates to a method of treating patients afflicted with acute renal failure. The method includes administering to a patient in need of treatment an effective amount of a thiol or reducible disulfide compound according to the formula set forth in the specification. Excerpt(s): This invention relates to a method for treating a patient suffering from acute renal failure. The method involves administering an effective amount of a disulfide or thiol-containing compound to a patient suffering from acute renal failure. Acute renal failure (ARF) is a severe, and often imminently life-threatening condition. There are many mechanisms which may be responsible for the pathogenesis of ARF. These include occlusions of the renal arteries, glomerular disease (glomerulonephritis, for one), infection (sepsis), disseminated intravascular coagulation (usually with cortical necrosis of the kidney), obstruction of urine flow due to tumors or other obstruction, acute tubular nephritis (ischemic or toxic), and others. Methods of treating acute renal failure vary, depending on the cause. In the case of sepsis-induced ARF, the mechanism is generally similar to shock, and the treatment methods include the infusion of antibiotics in efforts to kill the bacteria and/or endotoxins. Coagulation is treated with anti-coagulant agents and supportive measures such as catheterization. Toxic nephritis is generally treated with antidotal therapy, depending upon the type of poison. Web site: http://www.delphion.com/details?pn=US06172119__

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Method of treating rhabdomyolysis by administering hepatocyte growth factor Inventor(s): Kudo; Ikue (c/o Sumitomo Pharmaceuticals Co., Ltd., 1-98, Kasugade Naka 3-chome, Osaka-shi, Osaka 554-0022, JP), Nagano; Tomokazu (c/o Sumitomo Pharmaceuticals Co., Ltd., 1-98, Kasugade Naka 3-chome, Osaka-shi, Osaka 554-0022, JP) Assignee(s): None Reported Patent Number: 6,436,388 Date filed: February 24, 2000 Abstract: The present invention is drawn to a method of treating acute renal failure caused by rhabdomyolysis by administering a therapeutically effective amount of hepatocyte growth factor (HGF). The present invention is further drawn to a method of treating rhabdomyolysis by administering a therapeutically effective amount of hepatocyte growth factor (HGF). Excerpt(s): Acute renal failure is defined as having symptoms of azotemia, electrolyte imbalance, uremia and the like caused by acute renal dysfunction. Acute renal failure is classified into prerenal acute renal failure, renal acute renal failure and postrenal acute renal failure caused by renal dysfunction. Renal acute renal failure is classified into (1) vasculitis, glomerular lesion, (2) acute interstitial nephritis, (3) tubule obstruction and (4) acute renal failure in a narrow sense. Acute renal failure in a narrow sense is caused by acute tubular necrosis. The acute renal failure in a narrow sense results from (1)

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ischemia, (2) nephrotoxic substance, or (3) myolytic substance (e.g. myoglobin) and so on. Ischemic acute renal failure is caused by bleeding from surgery, shock, external injury, burn and the like. Experimental animal model for ischemic acute renal failure is exemplified by renal artery ligation. In the rat model, BUN (blood urea nitrogen) and serum creatinine are increased, HGF (Hepatocyte Growth Factor) mRNA expression is enhanced 6 to 12 hours after ischemia, and then HGF bioactivity in rat kidney and plasma is activated (American Journal of Physiology, 1993; 265; 61-69). Acute renal failure is also caused by a nephrotoxic substance such as anti-biotic agent, antitumor agent, contrast medium. An experimental animal model of acute renal failure caused by a nephrotoxic substance is made by administration of a compound such as mercurous chloride, cisplatin, and contrast medium to rats. Mercurous chloride administered rats show an increase of BUN and creatinine, enhancement of HGF mRNA expression and activity of HGF (Nephron 1996; 73: 735), as reported on ischemia model. It is suggested that HGF be involved in restoring a patient from renal failure. Web site: http://www.delphion.com/details?pn=US06436388__ •

Method of treatment and pharmaceutical composition Inventor(s): de Gasparo; Marc (Es Planches, CH), Webb; Randy Lee (Flemington, NJ) Assignee(s): Novartis AG (basel, Ch) Patent Number: 6,204,281 Date filed: July 8, 1999 Abstract: The invention relates to a method for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, myocardial infarction and its sequelae, supraventricular and ventricular arrhythmias, atrial fibrillation or atrial flutter, atherosclerosis, angina (whether stable or ustable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, hypertension in patients with NIDDM, secondary aldosteronism, primary and secondary pulmonary hyperaldosteronism, primary and pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), and stroke, comprising administering a therapeutically effective amount of combination of (i) the AT.sub.1 -antagonists valsartan or a pharmaceutically acceptable salt thereof and (ii) a Calcium channel blocker or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a mammal in need of such treatment and to corresponding pharmaceutical combination composition. Excerpt(s): (iii) a pharmaceutically acceptable carrier. Valsartan is specifically and generically disclosed in EP 0443983 A. The class of CCBs essentially comprises dihydropyridines (DHPs) and non-DHPs such as diltiazem-type and verapamil-type CCBs. Web site: http://www.delphion.com/details?pn=US06204281__

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Methods for treating hypertension and angina using salts of optically pure (-) amplodipine Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor Inc. (marlborough, Ma) Patent Number: 6,448,275 Date filed: April 24, 2001 Abstract: Methods and compositions are disclosed utilizing the optically pure (-) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. The (-) isomer of amlodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist such as cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure, without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. Excerpt(s): This invention relates to novel compositions of matter containing optically pure (-) amlodipine. These compositions possess potent activity in treating both systolic and diastolic hypertension while avoiding adverse effects including but not limited to edema of the extremities, headache and dizziness, which are associated with administration of the racemic mixture of amlodipine. Additionally, these novel compositions of matter containing optically pure (-) amlodipine are useful in treating angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure ----while avoiding the adverse effects associated with administration of the racemic mixture of amlodipine. Also disclosed are methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of amlodipine, by administering the (-) isomer of amlodipine to said human. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of planepolarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 12 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06448275__

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PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same Inventor(s): Jackson; Paul F. (Bel Air, MD), Li; Jia-He (Cockeysville, MD), Maclin; Keith M. (Baltimore, MD), Zhang; Jie (Ellicott City, MD) Assignee(s): Guilford Pharmaceuticals Inc. (baltimore, Md) Patent Number: 6,635,642 Date filed: September 1, 1998 Abstract: The present invention relates to PARP inhibitors, pharmaceutical compositions comprising the same, and methods of using the same to treat tissue damage resulting from cell damage or death due to necrosis or apoptosis, effect neuronal activities not mediated by NMDA toxicity; to treat neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and/or acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), organ damage due to transplantation, and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells. Excerpt(s): The present invention relates to inhibitors of the nucleic enzyme poly(adenosine 5'-diphospho-ribose) polymerase ["poly(ADP-ribose) polymerase" or "PARP", which is also sometimes called "PARS" for poly(ADP-ribose) synthetase]. More particularly, the invention relates to the use of PARP inhibitors to prevent and/or treat tissue damage resulting from cell damage or death due to necrosis or apoptosis; neural tissue damage resulting from ischemia and reperfusion injury; neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells. Poly(ADP-ribose) polymerase ("PARP") is an enzyme located in the nuclei of cells of various organs, including muscle, heart and brain cells. PARP plays a physiological role in the repair of strand breaks in DNA. Once activated by damaged DNA fragments, PARP catalyzes the attachment of up to 100 ADP-ribose units to a variety of nuclear proteins, including histones and PARP itself. While the exact range of functions of PARP has not been fully established, this enzyme is thought to play a role in enhancing DNA repair. During major cellular stresses, however, the extensive activation of PARP can rapidly lead to cell damage or death through depletion of energy stores. Four molecules of ATP are consumed for every molecule of NAD (the source of ADP-ribose) regenerated. Thus, NAD, the substrate of PARP, is depleted by massive PARP activation and, in the efforts to re-synthesize NAD, ATP may also be depleted.

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Web site: http://www.delphion.com/details?pn=US06635642__ •

Peptide analogues Inventor(s): Dong; Zheng Xin (Holliston, MA) Assignee(s): Societe DE Conseils DE Recherches ET D'applications Scientifiques, Sas (paris, Fr) Patent Number: 6,242,563 Date filed: June 28, 1999 Abstract: The present invention is directed to novel analogues of PACAP (Pituitary Adenylate Cyclase Activating Polypeptide) as described in the specification, which are agonists of the PACAP receptor and as such are useful in treating cerebrovascular ischemia, male impotence, motor neuron disease, neuropathy, pain, depression, anxiety disorders, brain trauma, memory impairments, dementia, cognitive disorder, central nervous system diseases (such as Parkinson's disease, Alzheimer's disease), migraine, neurodegenerative diseases, ischemic heart disease, myocardial infarction, fibrosis, restenosis, diabetes mellitus, muscle disease, gastric ulcer, stroke, atherosclerosis, hypertension, septic shock, thrombosis, retina disease, cardiovascular disease, renal failure and cardiac failure and the prevention of neuronal cell death in a mammal. This invention is also directed to pharmaceutical compositions useful therefor. Excerpt(s): The present invention is directed to novel analogues of PACAP (Pituitary Adenylate Cyclase Activating Polypeptide) and the use thereof for treating the conditions and or diseases as described herein. A review of PACAP and its physiological function is summarized in Christophe, J., Biochimica et Biophysica Acta, 1154, 183-199 (1993), as follows. At least two classes of PACAP receptors have been described in mammalian tissues and cell lines: type I PACAP-preferring receptors and type II receptors which bind PACAP-27, PACAP-38 and VIP (vasoactive intestinal peptide) (Cauvin, A., et al., Peptides, 11, 773-777 (1990) and Shivers, B. D., et al., Endocrinology, 128, 3055-3065 (1991)). In addition, the first type is capable to display two subtypes, and the second type can be tentatively divided into three subtypes. Web site: http://www.delphion.com/details?pn=US06242563__

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Process for preparing eprosartan using regioselective protection of 2,4-disubstitutedimidazole intermediates Inventor(s): Liu; Peng (Norristown, PA), Matsuoka; Richard T. (Norristown, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,458,963 Date filed: August 14, 2001 Abstract: The present invention relates to a process for preparing eprosartan, an angiotensin II receptor antagonist useful in the treatment of hypertension, congestive heart failure, and renal failure. The process for preparing eprosartan consists of three stages. These stages are: (Stage.dagger.1) the regioselective protection of 2-n-butyl-4formylimidazole; (Stage.dagger.2) the reaction between the product from Stage 1 and (2thienylmethyl)-propanedioic acid, mono-C.sub.1-4 alkyl ester; and (Stage.dagger.3) quaternary salt formation, followed by a basic work-up and an acidification. The

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efficiency of this synthetic sequence is particularly is particularly useful for the largescale production of eprosartan. Excerpt(s): The present invention relates to a process for preparing eprosartan. This compound is described in U.S. Pat. No. 5,185,351 as being an angiotensin II receptor antagonist useful in the treatment of hypertension, congestive heart failure and renal failure. U.S. Pat. No. 5,185,351 describes processes for the preparation of imidazole compounds, in particular the preparation of eprosartan. Although the processes described in this patent produce the imidazoles claimed therein, there was a need to improve these processes when preparing compounds, such as eprosartan, on a commercial scale. It has now been found that eprosartan can be prepared in three stages. These stages are: (Stage.dagger.1) the regioselective protection of 2-nbutylformylimidazole; (Stage.dagger.2) the reaction between the product from Stage 1 and (2-thienylmethyl)-propanedioic acid, mono-C.sub.1-4 alkyl ester; and (Stage.dagger.3) quaternary salt formation, followed by a basic work-up and an acidification. The efficiency of this synthetic sequence and the quality and yield of eprosartan are particularly important when preparing said product on a large scale for therapeutic use. Web site: http://www.delphion.com/details?pn=US06458963__ •

Pyrrolopyridinium derivatives Inventor(s): Araki; Norie (Kumamoto, JP), Horiuchi; Seikoh (Kumamoto, JP), Nakamura; Ko (Hyogo, JP) Assignee(s): Nippon Zoki Pharmaceutical Co., Ltd. (osaka, Jp) Patent Number: 6,613,537 Date filed: February 28, 2001 Abstract: The present invention is drawn to pyrrolopyridinium derivatives having a new structural skeleton, preferably containing an intramolecular hemiacetal, which is clearly different from any known Advanced Glycation Endproduct (AGE) and which, when present in an organism, has a bioactivity unlike the conventional AGE. The present invention provides pyrrolopyridinium derivatives and pharmaceutically acceptable salts thereof, an antibody prepared from said derivatives as a hapten, a method for the diagnosis of diabetes, diabetic complications, renal failure, dialysisrelated complications, amyloidosis, aging, diseases accompanied by aging, etc. using said derivatives or an antibody prepared therefrom and a method for evaluating effectiveness of pharmaceuticals used to treat diabetes, diabetes-related diseases, dialysis-related complications, aging, diseases accompanied by aging, etc. Excerpt(s): The present invention relates to novel pyrrolopyridinium derivatives; an antibody prepared from said derivatives as a hapten; a method for the diagnosis of diseases including diabetes, diabetic complications, amyoidosis, renal failure, dialysisrelated complications, aging, and diseases accompanied by aging, such as Alzheimer's disease, etc. by measuring said derivative or by measuring reactivity in the subject with an antibody prepared therefrom; and a method for evaluating the effectiveness of pharmaceuticals which are effective for treating diabetes, diabetic complications, amyloidosis, renal failure, dialysis-related complications, aging, and diseases accompanied by aging, such as Alzheimer's disease, etc. In 1968, glycosylhemoglobin (HbAlc), which is one of the minor components of hemoglobin was identified in vivo and was found to increase in patients diagnosed as having diabetes. With this discovery,

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the Maillard reaction was shown to occur with proteins in vivo. Despite having been studied mainly in the field of food chemicals, the biological and medical meaning of the Maillard reaction would now receive greatly increased public attention. The Maillard reaction may be classified into a former stage and a latter stage. In the former stage, a Schiff base is formed by the condensation of an amino group of a protein with an aldehyde group of a reducing sugar and is stabilized as a result of the Amadori rearrangement. In the latter stage, the rearranged Schiff Base is transferred, after a long series of reactions, to an Advanced Glycation Endproduct (AGE). The latter stage end products are characterized by fluorescence, a color change to brown and molecular crosslinking. In recent years, several studies on AGE have investigated the relationship between various diseases and AGE, which is produced particularly in the advanced stages of various diseases. Web site: http://www.delphion.com/details?pn=US06613537__ •

Treatment of acute renal failure by administration of N-acetylcysteine Inventor(s): Weinberg; Assa (344 N. Fairfax Ave., Los Angeles, CA 90036) Assignee(s): Weinberg; Assa (los Angeles, Ca) Patent Number: 6,355,682 Date filed: May 11, 2001 Abstract: A method for treating the damages caused by an acute renal failure is disclosed. The method according to the present invention comprises the administration of a therapeutically effective dose of N-acetylcysteine. Excerpt(s): The present invention relates to the field of treatment of patients who have been afflicted with acute renal failure. Acute renal failure or a rapid deterioration of the renal function is a common disturbance during which the kidneys' filtering capacity is lost and, as a result, a rapid accumulation of waste material, mainly nitrogenous products, occurs in the body. One of the most common causes for such renal failure is due to the reduction or interruption of the blood supply to the kidneys. Such reduction or interruption of the blood supply to the kidneys could be generally described as renal ischemia. There are multiple medical conditions that could cause the interruption of the renal circulation. Depending on the duration of an interruption, the outcome of an acute renal failure can be quite devastating. Every cardiovascular event associated with hypotension has a potential of causing a reduction in renal vascular supply. Other conditions, such as gastrointestinal hemorrage, extensive burn, trauma, surgery or anesthesia may also cause hypovolemia, i.e. a low blood volume. Hypovolemia may lead to a dramatic reduction in the blood circulating to the kidneys which may lead to a rapid deterioration in renal function. Web site: http://www.delphion.com/details?pn=US06355682__

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Tricyclic benzodiazepines as vasopressin receptor antagonists Inventor(s): Dyatkin; Alexey B. (Lansdale, PA), Hoekstra; William J. (Chapel Hill, NC), Maryanoff; Bruce E. (Forest Grove, PA), Matthews; Jay M. (Lansdale, PA) Assignee(s): Ortho-mcneil Pharmaceutical, Inc. (raritan, Nj) Patent Number: 6,713,475 Date filed: July 24, 2001 Abstract: The invention is directed to tricyclic benzodiazepines useful as vasopressin receptor antagonists for treating conditions involving increased vascular resistance and cardiac insufficiency. Pharmaceutical compositions comprising tricyclic benzodiazepines of the present invention and methods of treating conditions such as hypertension, congestive heart failure, cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, cerebral edema and ischemia, stroke, thrombosis, or water retention are also disclosed. Excerpt(s): This invention relates to novel tricyclic vasopressin receptor antagonists. More particularly, the compounds of the present invention interrupt the binding of the peptide hormone vasopressin to its receptors and are therefore useful for treating conditions involving increased vascular resistance and cardiac insufficiency. Vasopressin is a nonapeptide hormone that is secreted primarily from the posterior pituitary gland. The hormone effects its actions through membrane-bound V-1 and V-2 receptor subtypes. The functions of vasopressin include contraction of uterine, bladder, and smooth muscle; stimulation of glycogen breakdown in the liver; release of corticotropin from the anterior pituitary; induction of platelet aggregation; and central nervous system modulation of behaviors and stress responses. The V-1 receptor mediates the contraction of smooth muscle, and hepatic glycogenolytic and central nervous system effects of vasopressin. The V-2 receptor, presumably found only in the kidney, effects the antidiuretic actions of vasopressin via stimulation of adenylate cyclase. Elevated plasma vasopressin levels appear to play a role in the pathogenesis of congestive heart failure (P. A. Van Zwieten, Progr. Pharmacol. Clin. Pharmacol. 1990, 7, 49). As progress toward the treatment of congestive heart failure, nonapeptide vasopressin V-2 receptor antagonists have induced low osmolality aquaresis and decreased peripheral resistance in conscious dogs with congestive heart failure (H. Ogawa, J. Med. Chem. 1996, 39, 3547). In certain pathological states, plasma vasopressin levels may be inappropriately elevated for a given osmolality, thereby resulting in renal water retention and hyponatremia. Hyponatremia, associated with edematous conditions (cirrhosis, congestive heart failure, renal failure), can be accompanied by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Treatment of SIADH-compromised rats with a vasopressin V-2 antagonist has corrected their existing hyponatremia (G. Fujisawa, Kidney Int. 1993, 44(1), 19). Due in part to the contractile actions of vasopressin at the V-1 receptor in the vasculature, vasopressin V-1 antagonists have reduced blood pressure as a potential treatment for hypertension. Thus, vasopressin receptor antagonists could be useful as therapeutics in the conditions of hypertension, congestive heart failure/cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, cerebral edema and ischemia, stroke, thrombosis, and water retention. Web site: http://www.delphion.com/details?pn=US06713475__

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Use of prostaglandin (PGE2) receptor a (EP4) selective agonists for the treatment of acute and chronic renal failure Inventor(s): Paralkar; Vishwas M. (Madison, CT), Thompson; David D. (Gales Ferry, CT) Assignee(s): Pfizer Inc. (new York, Ny) Patent Number: 6,610,719 Date filed: January 29, 2001 Abstract: This invention is directed to methods and compositions of treating acute or chronic renal failure or dysfunction, or conditions caused thereby, comprising administering prostaglandin agonists, which are EP.sub.4 receptor selective prostaglandin agonists. Excerpt(s): The present invention relates to methods and pharmaceutical compositions comprising receptor selective prostaglandin (PGE.sub.2) agonists for the treatment of kidney diseases, such as chronic and acute renal failure or dysfunction, in animals, particularly mammals. More specifically, the present invention relates to such methods and pharmaceutical compositions comprising type 4 (EP.sub.4) receptor selective prostaglandin (PGE.sub.2) agonists. The naturally occurring prostaglandins are comprised of several biological entities including PBD, PGE, PGF, PGG, PGH and PGI. It has been well documented that prostaglandins have effects on many of the organs and systems of the body. In the kidney, the prostaglandins modulate renal blood flow and may serve to regulate urine formation by both renovascular and tubular effects. In clinical studies, PGE, has been used to improve creatinine clearance in patients with chronic renal disease, to prevent graft rejection and cyclosporine toxicity in renal transplant patients, to reduce the urinary albumin excretion rate and N-acetyl-beta-Dglucosaminidase levels in patients with diabetic nephropathy, and to improve urea clearance in healthy volunteers. PGE.sub.1 also has been administered intravenously during surgeries to prevent renal failure. Web site: http://www.delphion.com/details?pn=US06610719__

Patent Applications on Renal Failure As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to renal failure: •

A1 adenosine receptro antagonists Inventor(s): Lin, Ko-Chung; (Lexington, MA), Vu, Chi; (Arlington, MA) Correspondence: Fish & Neave; 1251 Avenue OF The Americas; 50th Floor; New York; NY; 10020-1105; US Patent Application Number: 20030220358 Date filed: May 27, 2003 Abstract: Compounds of Formula I and II are disclosed as antagonists of subtype A1 adenosine receptors. These compounds are useful for treatment of various diseases and

10

This has been a common practice outside the United States prior to December 2000.

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disorders, including systemic hypertension, renal failure, diabetes, asthma, an edematous condition, congestive heart failure, and renal dysfunction. 1 Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/250,658, filed Dec. 1, 2000, which is herein incorporated by reference. This invention relates to medicinal chemistry and pharmacology. More particularly, it relates to antagonists of the adenosine receptors, pharmaceutical compositions comprising these compounds and methods of making and using the same in the treatment of diseases. Adenosine is a ubiquitous biochemical messenger. Adenosine binds to and activates seven-transmembrane spanning G-protein coupled receptors, eliciting a variety of physiological responses. Adenosine receptors are divided into four known subtypes (i.e., A.sub.1, A.sub.2a, A.sub.2b, and A.sub.3). These receptor subtypes mediate different, and sometimes opposing, effects. Activation of the adenosine A.sub.1 receptor, for example, elicits an increase in renal vascular resistance, while activation of the adenosine A.sub.2a receptor elicits a decrease in renal vascular resistance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Acylated indanyl amines and their use as pharmaceuticals Inventor(s): Dharanipragada, Ramalinga M.; (Belle Meade, NJ), Safarova, Alena; (Tucson, AZ), Schonafinger, Karl; (Alzenau, DE), Strobel, Hartmut; (Liederbach, DE), Suzuki, Teri; (Tucson, AZ), Walser, Armin; (Tucson, AZ), Wohlfart, Paulus; (Bensheim, DE) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030055093 Date filed: February 13, 2002 Abstract: The present invention relates to acylated indanyl amines according to the general formula (I) 1wherein R.sup.1-R.sup.4 have the meanings given in the description, A is CH.sub.2, CHOH or CH--(C.sub.1-C.sub.3-alkyl), B is CH.sub.2 or CH-(C.sub.1-C.sub.3-alkyl), and R.sup.5 is an aryl or heteroaryl group, possibly substituted by the substituents listed in the description. These compounds are useful in the upregulation of endothelial nitric oxide synthase (eNOS), and may therefore be useful for the manufacture of medicaments for the treatment of cardiovascular diseases, stable or unstable angina pectoris, coronary heart disease, Prinzmetal angina, acute coronary syndrome, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes or diabetes complications, nephropathy or retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, restricted memory performance, a restricted ability to learn, or for the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives. Excerpt(s): Endothelial NO synthase (eNOS, NOS-III) belongs to a group of three isoenzymes which produce nitric oxide (NO) by oxidation of arginine. Endothelially released NO is of central importance in a number of key cardiovascular mechanisms. It has a vasodilating effect and inhibits the aggregation of platelets, the adhesion of leukocytes to the endothelium and the proliferation of intimal smooth muscle cells.

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Endothelial NO synthase is subject to physiological and pathophysiological regulation both at the transcriptional and at the post-transcriptional level. Enzyme already present in the endothelium may undergo calcium-dependent and calcium-independent activation through phosphorylation of specific amino acids, but also by direct interactions with specific proteins. Stimulators of this, usually transient, NO release are, extracellular arginine, 17.beta.-estrogen and the mechanical stimulus exerted on the luminal surface of the endothelium by the blood flow (shear stress). The latter additionally leads to regulation of eNOS at the transcriptional level. Thus, for example, Sessa et al. (Circ. Research 74 (1994) 349-353) were able by means of exercise training and the increase in shear stress associated therewith to obtain a marked increase in ecNOS. Whether regulation at the post-transcriptional level is relevant in vivo, is not unambiguously proved. Thus, for example, administration of a high arginine dose is followed by only a transient improvement in the endothelium-dependent vasorelaxation in patients with coronary heart disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anti fibrotic agent containing sphingosine 1-phosphate receptor agonist or sphingosine 1-phospate as active ingredient Inventor(s): Kishikawa, Katsuya; (Mishima-gun, JP), Matsumoto, Shigeru; (Mishimagun, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Suite 800; Washington; DC; 20037; US Patent Application Number: 20040063667 Date filed: September 15, 2003 Abstract: An anti fibrotic agent, comprising a sphingosine 1-phosphate (S1P) receptor agonist or sphingosine 1-phosphate (S1P) as an active ingredient. Since an S1P receptor agonist, particularly S1P, has activity of inhibiting fibrosis in various organs, it is useful in preventing and/or treating diseases caused by fibrosis in organs, such as pulmonary fibrosis, interstitial pneumonia, chronic hepatitis, hepatic cirrhosis, chronic renal failure, renal glomerulosclerosis, etc. Excerpt(s): Sphingolipid as one of the cell membrane-constituting lipid-soluble components contains two kinds, sphingomyelin and glycolipid. They are converted into ceramides enzymatically via sphingomyelinase and endoglycanase, and then metabolized into sphingosine by a ceramidase. Furthermore, the sphingosine is then converted into sphingosine 1-phosphate (hereinafter referred to as "S1P") by a sphingosine kinase. Studies on such intracellular metabolism of sphingolipid have been carried out since 1960's, but until now, S1P has been recognized only as one of the intermediate metabolic products in the sphingolipid metabolism. However, S1P is focused because its physiological activities are being revealed recently. For example, the followings are known as the activities possessed by S1P. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Autogenous vaccine derived from one's own hypothalamus of the brain & kidney's via a process known as liquefaction Inventor(s): Morton, Randall Aaron; (Laguna Niguel, CA) Correspondence: Randall Aaron Morton; 29881 Weatherwood; Laguna Niquel; CA; 92677-1945; US Patent Application Number: 20020155116 Date filed: April 23, 2001 Abstract: By extrapolation of tissue from the person affected, and then using the process of liquefaction, and from there creating an autogenous vaccine and injecting that vaccine 1 cc to the affected area would not only cure heart disease, strokes, renal failure, Chron's Disease, asthma, sugar diabetes and as a cure for paralyses would not pose rejection since it would be coming from one's own tissues. Excerpt(s): This invention involves the extrapolation of tissue from the hypothalamus of the brain and tissue from the medulla of the brain stem and tissue from the renal medulla of the kidney (which is located in the right kidney) and tissue from both the cortex of the brain and kidney from the person involved. Then, by using a process called liquefaction (which is a conversion of tissue to a fluid or semi fluid state), create an autogenous vaccine for the cure, treatment and prevention of heart disease, strokes, renal failure, Chron's Disease, asthma, sugar diabetes and as a cure for paralyses. The vaccine would be administered through injection of 1 cc to the affected area (s). Treatment of hear disease, strokes, renal failure, Chron's Disease, asthma, sugar diabetes and paralysis. Treatment of the above mentioned diseases have been dismal at best. In the case of heart disease, the common forms of treatment are angioplasty, which relieves blockage to the heart. This, however, must be repeated and is not a cure. Also, heart bypass surgery has been tried and that too had to be repeated and again has proven to be no cure for heart disease. Heart transplants have been tried, often times the body has rejected these hearts and again, this is not a cure. Each treatment is followed up by a regimen of drugs that those afflicted take for the duration of their lives only to experience severe side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Bicarbonate-based solutions for dialysis therapies Inventor(s): Colas, Jerome; (Bruxelles, BE), Divino, Jose; (Waterloo, BE), Elisabettini, Paola; (Fleurus, BE), Faict, Dirk; (Assenede, BE), Menneguerre, Jean-Paul; (Brussels, BE), Renaux, Christian; (Germain-en Laye, FR), Wilmet, Isabelle; (Vieux-Genappe, BE) Correspondence: Baxter Healthcare Corporation; Renal Division; 1 Baxter Parkway; Df33e; Deerfield; IL; 60015; US Patent Application Number: 20030138501 Date filed: January 11, 2002 Abstract: Bicarbonate containing solutions for use during medical treatment are provided. The bicarbonate containing solution of the present invention includes at least two separate components including a bicarbonate concentrate and an electrolyte concentrate which can be readily and sterilely mixed to form a ready-to-use formulation for patient administration, particularly as applied to the treatment of acute renal failure associated with critically ill patients in an intensive care setting.

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Excerpt(s): The present invention relates generally to medical treatments. More specifically, the present invention relates to bicarbonate-based solutions for use during dialysis therapies, such as continuous renal replacement therapies. A variety of different medical treatments are known and used to treat critically ill patients for acute renal failure (ARF) which is typically associated with multiple organ failure syndrome in intensive care settings. For example, traditional dialysis therapies, such as hemodialysis and peritoneal dialysis, are commonly used to treat ARF. However, because traditional dialysis therapies are known to have limited use with respect to the treatment of critically ill patients for ARF, the use of continuous renal replacement therapy in favor of traditional dialysis therapies has increased, particularly in intensive care settings. In this regard, a number of possible advantages with respect to CRRT in comparison to traditional dialysis therapies have been recognized. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Calcium glutarate supplement and phosphorus binder Inventor(s): Alexandrides, George; (San Antonio, TX), Walsdorf, Neill B. SR.; (San Antonio, TX) Correspondence: Thomas D. Paul; Fulbright & Jaworski, L.L.P.; 1301 Mckinney, Suite 5100; Houston; TX; 77010-3095; US Patent Application Number: 20030077331 Date filed: July 31, 2001 Abstract: Methods of controlling calcium intake and phosphate metabolism and metabolic acidosis in patients suffering from renal failure and associated hyperphosphatemia or patients predisposed to development of a hyperphosphatemic condition are provided. The method in accordance with this invention comprises administering to a patient a calcium glutarate compound. Therapeutic benefit can be realized in accordance with such method by administering the compound orally to a patient to increase available calcium and contact and bind with ingested phosphate in the patient's digestive tract, and thereby prevent its intestinal absorption. Excerpt(s): The present invention relates generally to calcium supplementation and controlling phosphate retention and particularly, to methods for treating patients on dialysis and suffering from renal failure and associated hyperphosphatemia. Phosphorus is the sixth most abundant element in the human body. It is critical for bone mineralization, cellular structure, genetic coding, and energy metabolism. Many organic and inorganic forms exist. Approximately 1,000 g of phosphorus is present in an adult, of which 80-90% is in bone. An additional 10-14% is intracellular and the remaining 1%, is extracellular. The phosphorus in plasma is 12-17% protein bound. Free serum compounds represent much less than 1% of the total body phosphorus content. This fraction also varies with shifts between the intracellular and extracellular compartments. Thus, serum phosphorus levels may not accurately reflect the total body phosphorus content. Levels are expressed in terms of serum phosphorus mass (mg/dL). One mg/dL of phosphorus is equal to 0.32 mmol of phosphate. The normal adult range is 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L). Levels are 50% higher in infants and 30% higher in children due to growth hormone effects. Hyperphosphatemia is an abnormally elevated serum phosphate level. Normal serum phosphate levels are in the range of 2.5 to 4.5 mg/dl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cell volume-regulated human kinase h-sgk Inventor(s): Lang, Florian; (Tubingen, DE), Waldegger, Siegfried; (Tubingen, DE) Correspondence: Michele M. Simkin; Foley & Lardner, Washington Harbour; Suite 500; 3000 K Street, N.W.; Washington; DC; 20007-5143; US Patent Application Number: 20030003559 Date filed: December 4, 2001 Excerpt(s): The present invention relates to the cloning and characterization of a human serine/threonine kinase (h-sgk: serum and glucocorticoid dependent kinase). The invention furthermore relates to reagents for diagnosing conditions associated with a change in cell volume and/or in "macromolecular crowding" in the body, such as, for example, hypernatremia, hyponatremia, diabetes mellitus, renal failure, hypercatabolism, hepatic encephalopathy, inflammation and microbial or viral infections. The present invention additionally relates to pharmaceuticals comprising the h-sgk, nucleic acids which code for the h-sgk, or receptors, in particular antibodies, which specifically bind to the h-sgk. Even when the extracellular osmolarity is constant, the constancy of the cell volume is continuously challenged due to transport across cell membranes and cellular metabolism, i.e. production and breakdown of osmotically active substances. Cell swelling and shrinkage disturb the intracellular environment by diluting and concentrating, respectively, cellular macromolecules which lead to extensive impairment of cellular functions. This is why cells have developed a large number of cell volume-regulating mechanisms. Cell swelling leads, in most tissues, to cellular release of ions due to activation of ion channels and KCl cotransport. Cell shrinkage conversely leads to cellular uptake of ions due to activation of NaCl/KCl cotransporter and Na.sup.+/H.sup.+ exchanger. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Combination therapy using antihypertensive agents and endothelin antagonists Inventor(s): Adams, Michael A.; (Kingston, CA), Hale, Taben M.; (Kingston, CA), Heaton, Jeremy P.W.; (Gananoque, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20040063719 Date filed: May 2, 2003 Abstract: The present invention provides a method for a more efficacious treatment of a vascular condition through the administration of a therapeutically effective amount of a combination of an anti-pressor agent, an endothelin antagonist, and a sex hormone for repetitive cycles of on/off-treatment. In one embodiment, the invention provides a method for the prevention of tolerance induced by an anti-pressor agent via the inclusion of an endothelin antagonist in a combination therapy approach to remodel vascular structure and treat vascular conditions associated with a male or female sexual dysfunction, atherosclerosis, renal failure, hypertension, congestive heart failure, diabetic nephropathy, and diabetic neuropathy. The anti-pressor agent comprises one or more compounds such as prostaglandin-E.sub.1, an ACE inhibitor, an angiotensin-II receptor antagonist, an.alpha.sub.1-adrenergic receptor antagonist, a.beta.-adrenergic receptor antagonist, a calcium channel blocker, an activator of guanylyl cyclase or adenyl cyclase, a phosphodiesterase inhibitor, and hydralazine. The endothelin

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antagonist comprises one or more compounds such as a peptidal endothelin antagonist, a non-peptidal endothelin antagonist, and an inhibitor of endothelin converting enzyme. Such a combination therapy approach enhances the efficacy of the anti-pressor agent and enables an increase in the frequency and duration of anti-pressor administrations for the long term treatment of vascular conditions. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 10/192,281, filed Jul. 9, 2002, which is a continuation of U.S. application Ser. No. 09/902,787, filed Jul. 12, 2001, now U.S. Pat. No. 6,458,797, which application is a continuation of U.S. application Ser. No. 09/382,749, filed Aug. 25, 1999, now U.S. Pat. No. 6,284,763, and which application claims priority to U.S. Provisional Application No. 60/098,178, filed Aug. 26, 1998. The present application claims priority to U.S. Provisional Application No. 60/377,917, filed May 2, 2002. All the foregoing applications are incorporated herein by reference in their entirety. The present invention relates to medical methods of treatment, pharmaceutical compositions, and use of antipressor agents, endothelial antagonists, and sex hormones to manufacture such pharmaceutical compositions. More particularly, the present invention is concerned with methods for providing more efficacious treatment regimens for the administration of agents which act in the long term management of sexual dysfunction in both males and females. The physiology of an erection or sexual arousal in both the male and female involves central nervous system initiation, neural pathway activation, and vascular smooth muscle relaxation. This signaling mediates vasodilation of the penile, clitoral labial, and vaginal arterial blood vessels and the trabecular meshwork of smooth muscle. The resulting decrease in vascular resistance promotes an increase in arterial inflow and the filling of the corpora cavernosa in the penis and clitoris. Subsequent to there being an appropriate high rate of inflow, the cavernosal "filling" results in occlusion of the sub-tunical veins and full rigidity. The rate of inflow is critical because if there is not enough volume change, venous occlusion can not take place. A selective structurally-based increase in penile resistance produces a substantial impediment to inflow. That is, if penile or clitoral vascular structure, or the vascular structure immediately "up-stream" from the genitalia, is more constrained than the rest of the circulation, there would be a "mismatching" of perfusion pressure and selective resistance, i.e. genital arterial insufficiency. On the other hand, it is likely that when hypertension is first established and there is a generalized up-regulation of structurallybased vascular resistance in all vessels, there would not be any deleterious effect on erectile function because of a "matching" between perfusion pressure and resistance. That is, despite the hypertrophy of the penile vasculature, the arterial pressure is proportionally elevated thereby allowing for adequate blood flow to the penis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Endothelin-antagonizing peptide Inventor(s): Bando, Chieko; (Tokyo, JP), Chiba, Shigeru; (Kawasaki-shi, JP), Ikemura, Toshihide; (Mishima-shi, JP), Kawamoto, Isao; (Hiratsuka-shi, JP), Kitamura, Shigeto; (Tokyo, JP), Makino, Mika; (Muroran-shi, JP), Matsuda, Yuzuru; (Tokyo, JP), Morishita, Yoshikazu; (Tokyo, JP), Ogawa, Tatsuhiro; (Kawasaki-shi, JP), Shibata, Kenji; (Kawasakishi, JP), Suzawa, Toshiyuki; (Yamato-shi, JP), Tanaka, Takeo; (Tokyo, JP), Tsukuda, Eiji; (Sunto-gun, JP), Yamaguchi, Kazuo; (Sagamihara-shi, JP), Yamasaki, Motoo; (Tokyo, JP), Yano, Keiichi; (Kawasaki-shi, JP), Yoshida, Mayumi; (Sagamihara-shi, JP) Correspondence: Antonelli Terry Stout And Kraus; Suite 1800; 1300 North Seventeenth Street; Arlington; VA; 22209 Patent Application Number: 20030055213 Date filed: January 2, 2001 Abstract: Disclosed in a peptide represented by the following formula (I):X-A-Trp-BGly-Thr-E-G-Y (I)whereinA represents Asn or Asp;B represents His or Lys;E represents Ala or Ser;G represents Ala or Pro;X represents X.sup.1-Gly or 1Y represents hydroxy, lower alkoxy, amino, 2whereineach of X.sup.1 and X.sup.3 represents hydrogen, benzyloxycarbonyl, t-butyloxycarbonyl or 9-fluorenylmethyloxycarbonyl, or carbonylsubstituted or unsubstituted lower alkanoyl;each of X.sup.2 and Y.sup.2 represents hydrogen;Y.sup.1 represents hydroxy, lower alkoxy or amino; orX.sup.1 and Y.sup.1, or X.sup.2 and Y.sup.2 are combined together to form a single bond as X.sup.1--Y.sup.1 or X.sup.2--Y.sup.2; andZ represents hydroxy, lower alkoxy, benzyloxy, benzhydryloxy, amino, 3whereZ.sup.2 is hydroxy, lower alkoxy, benzyloxy, benzhydryloxy or amino,Gly-Z.sup.1whereZ.sup.1 is hydroxy, lower alkoxy, benzyloxy, benzhydryloxy, amino, 4where Z.sup.2 is as defined previously, or Z.sup.1 is combined with X.sup.1 to form a single bond as X.sup.1--Z.sup.1,Ala-Z.sup.1where Z.sup.1 is as defined previously,Val-Z.sup.1where Z.sup.1 is as defined previously,Trp-Z.sup.1where Z.sup.1 is as defined previously,Trp-Gly-Z.sup.1where Z.sup.1 is as defined previously,TrpAsn-Tyr-Tyr-Trp-Z.sup.1where Z.sup.1 is as defined previously,Trp-Phe-Phe-Asn-TyrTyr-7Hyt-Z.sup.1where Z.sup.1 is as defined previously, and 7Hyt represents 7hydroxytryptophan,Trp-Ile-Ile-Trp-Z.sup.1where Z.sup.1 is as defined previously,TrpVal-Tyr-Phe-W-His-Leu-Asp-Ile-Ile-Trp-Z.sup.1where Z.sup.1 is as defined previously and W represents Ala, Ser or Cys,Trp-W-His-Leu-Asp-Ile-Ile-Trp-Z.sup.1where Z.sup.1 and W are as defined previously,Trp-Val-Tyr-Tyr-W-His-Leu-Asp-Ile-Ile-TrpZ.sup.1where Z.sup.1 and W are as defined previously,Trp-Leu-Tyr-Phe-W-His-GlnAsp-Val-Ile-Trp-Z.sup.1where Z.sup.1 and W are as defined previously,Trp-Val-TyrPhe-W-Phe-Phe-Asn-Tyr-Tyr-Trp-Z.sup.1where Z.sup.1 and W are as defined previously,Trp-Phe-Phe-Asn-Tyr-Tyr-W-His-Leu-Asp-Ile-Ile-Trp-Z.sup.1where Z.sup.1 is as defined previously,Trp-Phe-Phe-Asn-Tyr-Tyr-Asn-Ile-Ile-Trp-Z.sup.1where Z.sup.1 is as defined previously,J-Phe-M-Q-Tyr-R-T-Z.sup.1whereJ is Trp or a single bond,M is Phe or a single bond,Q is Asn or a single bond,R is Tyr or a single bond,T isTrp,Ala,Phe,Tyr,Trp-Trp,Asn-Tyr-Tyr-Trp,Trp-Asn-Tyr-Tyr-Trp,Try-Val-Tyr-Phe-WHis-Leu-Asp-Ile-Ile-Trp,where W is as defined previously, or a single bond,2 or more of J, M, Q, R and T are not a single bond simultaneously, and Z.sup.1 is as defined previously,or a pharmaceutically acceptable salt thereof.The peptide has endothelinantagonizing activity, and is therefore useful for treatment of hypertension, asthma, cerebral apoplexy, angina pectoris, acute renal failure, cardiac infarction, cerebral vasospasm, etc. Excerpt(s): The present invention relates to a novel peptide which has endothelinantagonizing activity, and an intermediate for its synthesis. The peptide has excellent

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endothelin-antagonizing activity, and is therefore useful for treatment of hypertension, asthma, cerebral apoplexy, angina pectoris, acute renal failure, cardiac infarction, cerebral vasospasm, etc. Endothelin is a cyclic peptide which possesses a strong, longlasting vasoconstricting effect, and is thought to be one of the substances responsible for hypertension, asthma, acute renal failure, cardiac infarction, cerebral apoplexy, angina pectoris and cerebral vasospasm. Consequently, a substance which antagonizes endothelin and inhibits its effects is expected to be useful for the treatment and prevention of these diseases. (wherein U represents D-Val or D-allo-Ile, R.sup.1 represents hydrogen or an amino-protective group, and R.sup.2 represents hydrogen or a carboxyl-protective group) exhibits the endothelin antagonism (Japanese Published Unexamined Patent Application No. 130299/91). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Eprosartan arginyl charge-neutralization-complex and a process for its preparation and formulation Inventor(s): Palepu, Nageswara R.; (Norristown, PA), Venkatesh, Gopadi M.; (King of Prussia, PA) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020137943 Date filed: December 12, 2001 Abstract: This invention relates to (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methy- l]1H-imidazol-5-yl]methylene-2-thiophenepropionic acid arginyl charge-neutralizationcomplex, a process for its production, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to a pharmaceutically active compound, a process for its production, compositions containing the compound and methods of using the compound in the treatment of certain disease states in mammals, in particular man. More specifically, the present invention relates to a charge-neutralization-complex of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1-H-imidazol-5-yl]methylene-2thiophenepropionic acid or its salt form, particularly, the methanesulfonate salt, and Larginine. Most particularly, this invention relates to a 1:1 to a 1:3 molar chargeneutralization-complex of (E)-.alpha.-[2-n-butyl-1-[(4-carbo- xyphenyl)methyl]-1Himidazol-5-yl]methylene-2-thiophenepropionic acid or its monomethanesulfonate salt and L-arginine (herein referred to as (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]meth- ylene-2-thiophenepropionic acid arginyl chargeneutralization-complex or eprosartan arginyl charge-neutralization-complex), a wet granulation process for preparing said charge-neutralization-complex, compositions containing this charge-neutralization-complex, and methods of using (E)-.alpha.-[2-nbutyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methy- lene-2-thiophenepropionic acid arginyl charge-neutralization-complex to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound (E).alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene-2thiophenepropionic acid is known by the name eprosartan and its methanesulfate salt is known as eprosartan mesylate. Eprosartan and eprosartan mesylate are the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses in Example 41 a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4-

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carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene-2-thiophenepropionic acid monomethanesulfonate. Additionally, the '351 patent discloses conventional techniques for formulating (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5yl]methy- lene-2-thiophenepropionic acid monomethanesulfonate and Examples 108111 specifically detail the preparation of certain formulations. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. Human clinical studies indicate (E)-.alpha.-[2-n-butyl-1-[(4-carbox- y phenyl)methyl]-1H-imidazol-5-yl]methylene-2thiophenepropionic acid monomethanesulfonate to be safe and well tolerated even up to doses of 800 mg per day. The time to maximum concentration is between 1 to 2.5 hours in fasted state and 2.54 hours in fed state. (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene-2-thiophenepropionic acid monomethanesulfonate exhibits a mean absolute bioavailability of approximately 13%. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and a device for determining the dry weight of a patient with kidney failure Inventor(s): Chamney, Paul; (Herts, GB) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20040064063 Date filed: November 7, 2003 Abstract: The invention relates to a method and a device for monitoring the fluid status of a patient with kidney failure. In case of renal failure all forms of ingested fluid accumulate in body tissues causing increased stress on the circulatory system. This surplus fluid has to be removed during a dialysis treatment by ultrafiltration of the blood. The amount of this surplus fluid or the weight corrected for this surplus fluid, i.e. the dry weight, is an important parameter for managing the fluid status of a dialysis patient. According to the invention the dry weight Wgt.sub.dry(t) of a patient at a time t is determined by determining the extracellular water volume ECV(t) of the patient at the time t, by determining the weight Wgt(t) of the patient at the time t and by deriving the dry weight Wgt.sub.dry(t) of the patient from an intersection of a function derived from the determined ECV(t) and Wgt(t) values with a previously established extracellular water volume (ECV) against dry weight (Wgt.sub.dry) reference relation representing healthy subjects. To obtain more accurate results it is also proposed to take into account a compartimental mass correction.DELTA.m(t). The invention also relates to a device for deriving the dry weight Wgt.sub.dry(t). Excerpt(s): The invention relates to a method and a device for monitoring the fluid status of a patient according to the preamble of claims 1 and 12, respectively. The kidneys carry out several functions for maintaining the health of a human body. First, they control the fluid balance by separating any excess fluid from the patient's blood volume. Second, they serve to purify the blood from any waste substances like urea or creatinine. Last not least they also control the levels of certain substances in the blood like electrolytes in order to ensure a healthy and necessary concentration level. In case of renal failure all forms of ingested fluid accumulate in body tissues causing increased stress on the circulatory system. This surplus fluid has to be removed during a dialysis treatment by ultrafiltration of the blood. If insufficient fluid is removed the long term consequenses can be severe, leading to high blood pressure and cardiac failure. Cardiac failure itself is many times more likely to occur in dialysis patients and it is thought that

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states of fluid overload are one of the major contributing factors. Removal of too much fluid is also dangerous since the dialysis patient becomes dehydrated and this invariably leads to hypotension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and system for determining kidney failure Inventor(s): Oort, Geeske Van; (Rosmalen, NL), Van Hove, Jos W.J.; (Schiedam, NL) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030083585 Date filed: October 26, 2001 Abstract: A method of determining kidney failure in a patient using an implantable medical device is described. In one embodiment, a first magnitude of a first polarization signal is measured. An additional magnitude of an additional polarization signal is measured after a first interval. A deflection differential between the first magnitude and the additional magnitude is determined and kidney failure in the patient is determined when the deflection differential is greater than an established threshold. Excerpt(s): The present invention relates to the field of implantable medical devices. More particularly, the present invention relates to cardiac pacing systems that are capable of measure and compare polarization signals to thereby determine an occurrence of a kidney failure. Implantable pulse generators (or IPGS) are well known in the prior art. After a stimulus in the heart, a charge builds up at the electrode tip, which results in a polarization signal that decays over time. While an initial magnitude of the polarization signal is dependent upon the configuration of the electrode as well as any fibrosis around the electrode tip, ionic concentration in the blood ambient the heart is a major factor in the generation of the initial magnitude. For a patient having a significant risk of experiencing kidney failure, the ionic concentration may increase with each succeeding dialysis of the patient. However, the medical arts have failed to utilize various measurements of the polarization signal to ascertain any increases in the ionic concentration with each succeeding dialysis of the patient. Thus, prior to the present invention, a need existed in the medical arts for facilitating a determination of a kidney failure by a patient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for treating renal disease, and pharmaceutical composition for treating renal disease Inventor(s): Nakanishi, Tsutomu; (Kanagawa, JP) Correspondence: Sughrue, Mion, Zinn, Macpeak & Seas, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037-3213; US Patent Application Number: 20020155165 Date filed: April 24, 2001 Abstract: A method for treating a patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required, comprising combining a peritoneal dialysis and an administration of a spherical carbon, is disclosed.

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Excerpt(s): The present invention relates to a method for treating a renal disease, and a pharmaceutical composition for treating a renal disease. More particularly, a method for ameliorating a chronic renal failure by a combination of a dialysis therapy and a spherical activated carbon administration, and a pharmaceutical composition for treating a chronic renal failure by a combination of a dialysis therapy and a spherical activated carbon administration. A normal kidney excretes waste materials, regulates an amount of humors (water content), provides an electrolyte balance, an acid-base equilibrium, and blood pressure, and produces hormones. A condition wherein the kidney is prevented from functioning normally, as above, and thus a homeostasis is not maintained, is called a renal failure. An acute renal failure is curable, whereas a chronic renal failure is an irreversible and progressively pathologic state. When a patient suffers a chronic renal failure, the renal functions are not recovered, and he or she will inevitably suffer from uremia. It is believed that it is impossible to heal or recover a chronic renal failure, but only to delay a worsening rate, or retard a presence of symptoms of uremia. The functions of a kidney can be evaluated by one of several indexes, i.e., an excreting function, which is one of the most important functions. The index of the excreting function is, usually, an endogenous creatinine clearance (Ccr) that corresponds nearly to an amount of a glomerular filtration. Ccr indicates a renal excreting function for a creatinine that is a metabolite of a muscle, and can be regarded as a representative or standard value of the excreting function of a kidney. A normal value of Ccr is 70 to 130 mL/min. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treatment of renal disease Inventor(s): Lazarus, J. Michael; (Wellesley Hills, MA) Correspondence: Stanley J. Gradisar; Suite 4100; 1801 California Street; Denver; CO; 80202; US Patent Application Number: 20040048837 Date filed: September 6, 2002 Abstract: A method for reducing mortality in renal failure patients such as dialysis patients by administering paricalcitol in place of calcitriol, preferably without regard to the secondary hyperparathyroidism, calcium or phosphate status of the patient. Excerpt(s): This invention relates to the treatment of renal disease using a Vitamin D analogue to enhance survival and reduce mortality. Chronic renal disease, sometimes called "kidney failure," is a serious and prevalent health problem affecting millions of individuals. At the extreme, called End State Renal Disease (or "ESRD"), these toxin build-ups can, and do, poison and kill the patient. Chronic renal disease is commonly caused by diabetes, but can also be caused by hypertension, immunologic disorders, genetic disorders, or nephrotoxic drugs. Because the kidneys process and remove toxins and other wastes from the bloodstream, such as urea and creatinine, the result of progressive kidney disease is a build-up of these waste products. This build-up produces a variety of detrimental chemical imbalances in the patient that affect physiological and neuropsychiatric function, producing many symptoms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of measuring lipid components and method of examining of renal failure Inventor(s): Hiura, Hisahide; (Kakogawa, JP), Hotta, Osamu; (Sendai, JP), Shirahase, Yasushi; (Kobe, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030017523 Date filed: August 7, 2002 Abstract: The problems of the present invention are to provide a simple and convenient means for the examination of renal failure and to provide a method for the measurement of a lipid component in urine utilizing the said examining means.Means for solving the problems according to the present invention is a method for the measurement of a lipid component contained in urine and it provides a method for measurement of a lipid component in urine which is characterized in using a surfaceactive agent in a sufficient amount for solubilizing the insoluble fat in urine and in using an enzyme acting the lipid component. It also provides a simple and convenient means for the examination of renal failure by the measurement of a lipid component contained in urine, by the measurement of lipoproteins in urine and/or apoproteins in urine in addition to the above measurement and by a combination of measurement of surface antigen of leukocyte contained in urine therewith. Excerpt(s): The present invention relates to a method for the measurement of lipid component in urine and to a reagent for the measurement. The present invention further relates to a examination means for renal failure utilizing the said method for the measurement. Components contained in urinary sediment are diversified such as components derived from kidney, components mingled from urinary tract and crystalline components separated out in urine. Checking the type and the amount of the sediment is very important in judging the diseases of kidney and urinary tract and in knowing their degree. They are usually carried out by an observation under a microscope by a dyeing method. There are also shown that pathological diagnosis of IgA nephropathy is possible by checking the surface antigen of macrophage in urine (Rinsho Kensa, volume 42, 588.about.590, 1998) and that examination of renal failure is possible by judging the fat particle and oviform fat body (hereinafter, sometimes referred to as just "fat body") in urine by means of dyeing off at in the urinary sediment (Kensa to Gijutsu, volume 26, 441-446, 1998). Further, in macrophage in a big size appeared in urine, surface antigen CD14 of leukocyte is negative while 25F9 is positive and that is greatly different from the usual macrophage where CD14 is positive while 25F9 is negative. In addition, it is shown that fat particle and oviform fat body belong to microphage in a big size and it is mentioned that measurement of them is useful as the examination for renal failure (Rinsho Byori, volume 47, Issue for General Meeting, 73, 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating anemia caused by ribavirin treatment of hepatitis C using erythropoietin alpha Inventor(s): Dieterich, Douglas T.; (Garden City, NY) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20030032590 Date filed: May 21, 2001 Abstract: Claimed and disclosed in a new use for a previously approved drug: erythropoietin. The present invention teaches using Erythropoetin to treat anemia caused by the combined treatment of Ribavirin and alpha-interferon. Erythropoetin has previously been approved for the treatment of anemia caused by cancer chemotherapy, renal failure and HIV. It has not been used for anemia caused by ribavirin. Ribavirin is part of a two-drug regimen now used to treat hepatitis C along with alpha interferon. The principal side effect of ribavirin is a hemolytic anemia. In the past, mangement of that anemia was done by dose reduction of the ribavirin, sometimes resulting in reversal of part of the anemia. It has become particularly important in light of new data, to maximize the dose of ribavirin given to persons undergoing treatment for hepatitis C to ensure a successful eradication of hepatitis C. Excerpt(s): The present invention is directed to a new use for Erythropoetin ("EPO"), such as EPO alpha, for treating hepatitis C and/or anemia caused by hepatitis C treatment. Accordingly, the invention involves using EPO with hepatitis C treatment, such as Ribavirin ("RBV") and/or interferon such as alpha-interferon (".alpha.-IFN" or "IFN"); and thus, the invention pertains to methods involving administration of EPO, RBV and.alpha.-IFN, or EPO and RBV, and compositions and kits containing EPO, RBV and.alpha.-IFN or EPO and RBV. Various documents are cited herein, e.g., in the text and/or in a reference section. There is no admission that any of the various documents cited in this text are prior art as to the present invention. Any document having as an author or inventor person or persons named as an inventor herein is a document that is not by another as to the inventive entity herein. All documents cited in this text ("herein cited documents") and all documents cited or referenced in herein cited documents are hereby incorporated herein by reference. All specifications, manufacturer's data sheets, and the like for products referenced herein, and all documents cited therein, are hereby incorporated herein by reference. Erythropoietin ("EPO") is one of the red blood cell stimulating factors in the human body. Recombinant technology has made manufacture of this stimulating factor colony possible and its use in treating anemia caused by cancer chemotherapy, acquired immune deficiency syndrome ("AIDS") and renal failure. The recombinant product has been shown to be biologically identical to human erythropoietin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of use of erythropoietin to treat ischemic acute renal failure Inventor(s): Westenfelder, Christof; (Salt Lake City, UT) Correspondence: Justin B. Rand; C/o Brinks Hofer Gilson & Lione; P.O. Box 10395; Chicago; IL; 60610; US Patent Application Number: 20030083251 Date filed: November 1, 2001

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Abstract: Recombinant erythropoietin is used in a method to prevent ischemic acute renal failure in patients at risk for developing ischemic acute renal failure and to treat fully-developed ischemic acute renal failure. The method is also used to prevent harmful cell apoptosis in renal tubular cells and to stimulate mitogenesis and motogenesis in renal tubular cells. The method comprises the administration of a composition of recombinant erythropoietin in a pharmacologically acceptable carrier to a patient for the purpose of preventing the development of ischemic acute renal failure, treating established acute renal failure, preventing harmful cell apoptosis in renal tubular cells. Excerpt(s): This invention relates to a method of use of a composition of matter. More particularly, the invention relates to a novel method of using a pharmaceutical composition comprising erythropoietin for treating ischemic acute renal failure (ARF) and for preventing the onset of ischemic ARF. Clinical acute renal failure (ARF) remains a common and serious complication associated with high morbidity and mortality. Moderately effective measures to prevent ARF include volume expansion, and in renal transplants, mannitol administration. The uremic state, volume and electrolyte disturbances can be readily corrected by hemodialysis, and outcomes are improved when more biocompatible dialysis membranes are used. In addition, administration of atrial natriuretic peptide has been found to speed the improvement of renal function in some patients with ARF. In the induction phase of ARF, cell necrosis, apoptosis, and sub-lethal injury are observed [1,2,3,4,5,6]. These effects are thought to collectively contribute to the loss of renal function via pathological activation of tubuloglomerular feedback, back leak of ultrafiltrate, tubular obstruction and ineffective transport by partially depolarized tubular cells [1,2,3,4,5,6]. In the repair phase of ARF, reepithelialization of injured tubules is accomplished by migration of cells ("motogenesis") into deepithelialized nephron segments, cell proliferation ("mitogenesis"), and redifferentiation of newly generated and sublethally injured tubular cells [1,6,7]. Anabolic mechanisms and improvement of intrarenal hemodynamics are also critical to functional recovery [1,2,8,9,10]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for the diagnosis and treatment of hematological disorders using 2777 Inventor(s): Carroll, Joseph M.; (Cambridge, MA) Correspondence: Millennium Pharmaceuticals, INC.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030091571 Date filed: October 28, 2002 Abstract: The present invention relates to methods and compositions for the diagnosis and treatment of hematological disorders, including, but not limited to, apalstic anemia, hemophilia, sickle cell anemia, thalassisemia, blood loss and other blood disorders, e.g., blood diorders related to bone marrow irradiation or chemotherapy treatment or renal failure. The invention further provides methods for identifying a compound capable of treating a hematological disorder. The invention also provides methods for identifying a compound capable of modulating a hematopoietic cell activity. Yet further, the invention provides a method for modulating a hematopoietic cell activity. In addition, the invention provides a method for treating a subject having a hematological disorder characterized by aberrant 2777 polypeptide activity or aberrant 2777 nucleic acid

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expression. In another aspect, the invention provides methods for increasing hematopoietic cell proliferation in a subject and methods for modulating hematopoietic cell apoptosis in a subject. Excerpt(s): This application claims priority to U.S. provisional application No. 60/335,251, filed Oct. 31, 2001, the entire contents of which are incorporated herein by reference. Hematological disorders are blood associated disorders. Blood is a highly specialized tissue which carries oxygen and nutrients to all parts of the body and waste products back to the lungs, kidneys and liver for disposal. Thus, blood maintains communication between different parts of the body. Blood is also an essential part of the immune system, crucial to fluid and temperature balance, a hydraulic fluid for certain functions and a highway for hormonal messages. All blood cells in adults are produced in the bone marrow. Red cells, white cells and platelets are produced in the marrow of bones, especially the vertebrae, ribs, hips, skull and sternum. These essential blood cells fight infection, carry oxygen and help control bleeding. Specifically, red blood cells are disc-shaped cells containing hemoglobin, which enables these cells to pick up and deliver oxygen to all parts of the body. White blood cells are the body's primary defense against infection. They can move out of the blood stream and reach tissues being invaded. Platelets are small blood cells that control bleeding by forming clusters to plug small holes in blood vessels and assist in the clotting process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for treating diseases associated with excesses in ACE Inventor(s): Moskowitz, David W.; (St. Louis, MO) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20030040509 Date filed: August 6, 2002 Abstract: Over 40 common diseases, in addition to congestive heart failure (CHF) due to hypertension (HTN) or non-insulin dependent diabetes mellitus (type II diabetes mellitus) (NIDDM), atherosclerotic peripheral vascular disease (ASPVD) due to HTN or NIDDM, and chronic obstructive pulmonary disease; emphysema (COPD), are associated with the ACE D/D genotype and should also respond to an adequate tissueinhibitory dose of ACE inhibitors such as quinapril. Several of these diseases have now been successfully treated using higher than normal dosages of ACE inhibitors, especially hydrophobic ACE inhibitors, with good outcomes. ACE inhibitors have also been found to be useful in inhibiting apoptosis and aging in general. Dosages that have been utilized are typically greater than quinapril at a dose of 40 to 80 mg/day, i.e. up to 1 mg/kg per day for a "typical" 80 kg patient. New formulations of ACE inhibitors have been developed for these higher dosages, including 80 mg tablets, controlled and/or sustained release formulations, and formulations containing a second active agent such as a diuretic, or a compound such as furosemide 20 mg/day (for creatinine <2.5 mg/dl) or furosemide 40 mg/day (for creatinine >2.5 mg/dl), to prevent fluid retention and congestive heart failure in patients with renal failure. The ACE inhibitors can also be combined with an angiotensin receptor blocker. Excerpt(s): This application claims priority to U.S. S. No. 60/310,064 filed Aug. 6, 2001; U.S. S. No. 60/347,905 filed Jan. 15, 2002; U.S. S. No. 60/347,013 filed Jan. 11, 2002; U.S. S. No. 60/350,563 filed Jan. 24, 2002; U.S. S. No. 60/352,484 filed Jan. 30, 2002; U.S. S. No.

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60/352,072 filed Jan. 28, 2002; and U.S. S. No. 60/352,074 filed Jan. 28, 2002; U.S. S. No. 60/378,467 filed May 8, 2002; U.S. S. No. 60/379,796 filed May 13, 2002; and U.S. S. No. 60/380,741 filed May 16, 2002. The present invention is generally in the field of methods and compositions for treatment of chronic disease. Angiotensin converting enzyme (encoded by the gene DCP1, also known as ACE) catalyses the conversion of angiotensin I to the physiologically active peptide angiotensin II, which controls fluidelectrolyte balance and systemic blood pressure. Because of its key function in the reninangiotensin system, many association studies have been performed with DCP1. Nearly all studies have associated the presence (insertion, I) or absence (deletion, D) of a 287-bp Alu repeat element in intron 16 with the levels of circulating enzyme or cardiovascular pathophysiologies. Many epidemiological studies suggest that the DCP1*D allele confers increased susceptibility to cardiovascular disease; however, other reports have found no such association or even a beneficial effect. Rieder, et al., Nat Genet 22(1):59-62 (1999), reports the complete genomic sequence of DCP1 from 11 individuals, representing the longest contiguous scan (24 kb) for sequence variation in human DNA, and identifies 78 varying sites in 22 chromosomes that resolved into 13 distinct haplotypes. Of the variant sites, 17 were in absolute linkage disequilibrium with the commonly typed Alu insertion/deletion polymorphism, producing two distinct and distantly related clades. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions of bioartifical kidney suitable for use in vivo or ex vivo Inventor(s): Humes, H. David; (Ann Arbor, MI) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030119184 Date filed: December 11, 2002 Abstract: A novel cell seeded hollow fiber bioreactor is described as a potential bioartificial kidney. Endothelial cells along with pericyte, vascular smooth muscle, and/or mesangial cells or any mesenchymally derived support cells are seeded along a hollow fiber in a perfused bioreactor to reproduce the ultrafiltration function and transport function of the kidney. Maintenance of tissue specific function and ultrastructure suggest that this bioreactor provides an economical device for treating renal failure. Excerpt(s): Applicants hereby claim as priority U.S. Provisional Application Serial No. 60/027,495 filed on Sep. 30, 1996. The present invention provides a BIOARTIFICIAL kidney comprising (1) a filtration device comprising endothelial cells and pericyte cells and (2) a tubule processing device. An implantable epithelial cell system derived from immortalized cells grown as confluent monolayers along the luminal surface of impermeable polymeric hollow fibers has been described as a first step for tubule functional replacement (Ip and Aebischer, Artificial Organs 13:58-65, 1989, incorporated herein by reference). Unfortunately, immortalized cells do not possess the full range of function of primary renal cells. Critical to development of functional renal tissue is the isolation and growth in vitro of primary cell lines. Primary cell lines should possess characteristics such that they exhibit a high capacity for self renewal. Preferably, the primary cell lines should possess stem cell-like characteristics such that they have the ability to differentiate under defined conditions into specialized cells having the correct structure and functional components of a physiologic kidney (Hall and Watt,

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Development 106:619-633, 1989; Potten and Loeffler, Development 110:1001-1020, 1990; Garlick et al., J. Invest. Dermatol. 97(5):824-829, 1991; all incorporated herein by reference). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and kits for improving vascular health Inventor(s): Day, Wesley W.; (San Diego, CA), Lee, Andrew G.; (Old Lyme, CT), Thompson, David D.; (Gales Ferry, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020156090 Date filed: October 15, 2001 Abstract: The present invention provides methods and kits for improving or maintaining vascular health, including preventing myocardial infarction or stroke; maintaining or improving vascular reactivity; treating acute or chronic renal failure, peripheral arterial occlusive disease, coronary artery disease, or Raynaud's phenomenon; or lowering plasma levels of Lp(a) using an estrogen agonist/antagonist. Excerpt(s): This application claims priority of U. S. provisional application number 60/241,532, filed Oct. 17, 2000. This invention relates to methods and kits for improving vascular health, including preventing myocardial infarction or stroke; maintaining or improving vascular reactivity; treating acute or chronic renal failure, peripheral arterial occlusive disease, coronary artery disease, or Raynaud's phenomenon; or lowering plasma levels of Lp(a) using an estrogen agonist/antagonist. In premenopausal women, 17.beta.-estradioi produced by the ovaries is the chief circulating estrogen. Serum estradiol concentrations are low in preadolescent girls and increase at menarche. In women, they range from about 100 pg per milliliter (367 pmol per liter) in the follicular phase to about 600 pg per milliliter (2200 pmol per liter) at the time of ovulation. They may rise to nearly 20,000 pg per milliliter (70,000 pmol per liter) during pregnancy. After menopause, serum estradiol concentrations fall to values similar to or lower than those in men of similar age (5 to 20 pg per milliliter [18 to 74 pmol per liter]) (Yen, S. S. C. and Jaffe, R. B., eds. Reproductive Endocrinology: Physiology, Pathophysiology and Clinical Management, 3rd ed. Philadelphia: W. B. Saunders, (1991)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for production of growth-promoting proteins and peptides for kidney epithelial cells Inventor(s): Toback, F. Gary; (Chicago, IL), Walsh-Reitz, Margaret M.; (River Forest, IL) Correspondence: Barnes & Thornburg; 2600 Chase Plaza; 10 South Lasalle Street; Chicago; IL; 60603; US Patent Application Number: 20030176340 Date filed: November 22, 2002 Abstract: Novel growth peptides derived from protein factors having molecular weights of about 22 and 45 kDa stimulate mitogenic activity of epithelial, but not fibroblastic cells, in particular, kidney epithelial cells. A source of the factors is scrape-wounded

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kidney epithelial cells in culture. Synthetic peptides having sixteen amino acids or less, in particular a hexapeptide, YPQGNH (SEQ ID NO: 2) maintain the mitogenic activity. The peptide AQPYPQGNHEASYG (14-Ser) (SEQ ID NO: 15) is effective in reversing acute renal failure in animals. The growth-promoting characteristics of the 22 and 45 kDa proteins and the peptides are useful in treating and diagnosing patients with kidney disease. Nucleotide sequences that encode the factor are useful to develop probes to locate similar factors, to identify genetic disorders involving the factor, and to produce the factor by genetic recombinant methods. The nucleotide sequences and fragments thereof, are also useful for diagnosis and treatment of kidney disorders. Excerpt(s): This application claims priority to U.S. Ser. No. 08/974,775 filed Nov. 20, 1997 now U.S. Pat. No. 6,096,706 issued Aug. 1, 2002 and U.S. Ser. No. 09/590,864 for which claims have been allowed and the issue fee paid. Novel growth peptides derived from protein factors having molecular weights of about 22 and 45 kDa stimulate mitogenic activity of epithelial, but not fibroblastic cells, in particular, kidney epithelial cells. Acute renal failure is a serious disease associated with high mortality for which no "real" treatment currently exists. Acute renal failure is defined as the abrupt disruption of previously normal kidney function. It is caused by a wide variety of mechanisms including circulatory failure (shock), vascular blockade, glomerulonephritis, and obstruction to urine flow. In addition it can occur following surgery, trauma, sepsis, or with certain medications, particularly antibiotics and anticancer agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating hypertension, angina, and congestive heart failure using of optically pure (-) amlodipine Inventor(s): Young, James W.; (Palo Alto, CA) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030050328 Date filed: July 29, 2002 Abstract: Methods and compositions are disclosed utilizing the optically pure (-) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. The (-) isomer of amlodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist such as cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure, without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. Excerpt(s): This invention relates to novel compositions of matter containing optically pure (-) amlodipine. These compositions possess potent activity in treating both systolic and diastolic hypertension while avoiding adverse effects including but not limited to edema of the extremities, headache and dizziness, which are associated with administration of the racemic mixture of amlodipine. Additionally, these novel compositions of matter containing optically pure (-) amlodipine are useful in treating angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial

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infarction, renal impairment and acute renal failure--while avoiding the adverse effects associated with administration of the racemic mixture of amlodipine. Also disclosed are methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of amlodipine, by administering the (-) isomer of amlodipine to said human. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of planepolarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 12 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treatment and pharmaceutical composition Inventor(s): Ksander, Gary Michael; (Amherst, NH), Webb, Randy Lee; (Flemington, NJ) Correspondence: Thomas Hoxie; Novartis, Corporate Intellectual Property; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030144215 Date filed: January 14, 2003 Abstract: The invention relates a pharmaceutical composition comprising a combination of:(i) the AT 1-antagonist valsartan or a pharmaceutically acceptable salt thereof; and(ii) a NEP inhibitor or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable carrier and to a method for the treatment or prevention of a condition or diseaseselected from the group consisting of hypertension, heart failure, such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction, such as Alzheimer's, glaucoma and stroke, comprising administering a therapeutically effective amount of the pharmaceutical composition to a mammal in need thereof. Excerpt(s): The renin angiotensin system is a complex hormonal system comprised of a large molecular weight precursor, angiotensinogen, two processing enzymes, renin and angiotensin converting enzyme (ACE), and the vasoactive mediator angiotensin II (Ang II). See J. Cardiovasc. Pharmacol., Vol. 15, Suppl. B, pp. S1-S5 (1990). The enzyme renin

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catalyzes the cleavage of angiotensinogen into the decapeptide angiotensin I, which has minimal biological activity on its own and is converted into the active octapeptide Ang II by ACE. Ang II has multiple biological actions on the cardiovascular system, including vasoconstriction, activation of the sympathetic nervous system, stimulation of aldosterone production, anti-natriuresis, stimulation of vascular growth and stimulation of cardiac growth. Ang II functions as a pressor hormone and is involved the pathophysiology of several forms of hypertension. The vasoconstrictive effects of angiotensin II are produced by its action on the non-striated smooth muscle cells, the stimulation of the formation of the adrenergenic hormones epinephrine and norepinephrine, as well as the increase of the activity of the sympathetic nervous system as a result of the formation of norepinephrine. Ang II also has an influence on electrolyte balance, produces, e.g., anti-natriuretic and anti-diuretic effects in the kidney and thereby promotes the release of, on the one hand, the vasopressin peptide from the pituitary gland and, on the other hand, of aldosterone from the adrenal glomerulosa. All these influences play an important part in the regulation of blood pressure, in increasing both circulating volume and peripheral resistance. Ang II is also involved in cell growth and migration and in extracellular matrix formation. Ang II interacts with specific receptors on the surface of the target cell. It has been possible to identify receptor subtypes that are termed, e.g., AT 1- and AT 2-receptors. In recent times great efforts have been made to identify substances that bind to the AT 1-receptor. Such active ingredients are often termed Ang II antagonists. Because of the inhibition of the AT 1receptor such antagonists can be used, e.g., as anti-hypertensives or for the treatment of congestive heart failure, among other indications. Ang II antagonists are therefore understood to be those active ingredients which bind to the AT 1-receptor subtype. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use Inventor(s): De Tejada, Inigo Saenz; (Madrid, ES), Earl, Richard A.; (Westford, MA), Garvey, David S.; (Dover, MA), Khanapure, Subhash P.; (Clinton, MA) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20030023087 Date filed: August 13, 2002 Abstract: The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as

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hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS). Excerpt(s): This is a continuation-in-part of U.S. application Ser. No. 09/145,142, filed Sep. 1, 1998, allowed, which is a continuation-in-part of U.S. application Ser. No. 08/740,764, filed Nov. 1, 1996, issued as U.S. Pat. No. 5,874,437; and is a continuation-inpart of PCT/US97/19870, filed Oct. 31, 1997, which claims priority to U.S. application Ser. No. 08/740,764, filed Nov. 1, 1996, issued as U.S. Pat. No. 5,874,437. The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions comprising at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one phosphodiesterase inhibitor, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, and glucoma, and diseases characterized by disorders of gut motility, such as irritable bowel syndrome (IBS). Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265-277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorgement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male, vasodilation of the cavernosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of

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females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387-391 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel assay Inventor(s): Brown, Andrew James; (Stevenage, GB), Wise, Alan; (Stevenage, GB) Correspondence: David J Levy, Corporate Intellectual Property; Glaxosmithkline; Five Moore DR., PO Box 13398; Research Triangle Park; NC; 27709-3398; US Patent Application Number: 20030113810 Date filed: October 8, 2002 Abstract: This invention relates to a method for identification of an agent that modulates activity of G-protein coupled receptor 41 (GPR 41), or G-protein coupled receptor 42 (GPR 42) which method comprises: (i) contacting a test agent with GPR 41, GPR42 or a variant of either thereof which is capable of coupling to a G-protein; and (ii) monitoring for GPR 41 or GPR 42 activity in the presence of a G-protein; thereby determining whether the test agent modulates GPR 41 or GPR 42 activity. An agent identifiable by this method is provided for use in the treatment of dyslipidaemia, coronary heart disease, atheroselerosis, thrombosis or obesity, angina, chronic renal failure, peripheral vascular disease, stroke, type II diabetes or metabolic syndrome (syndrome X). Excerpt(s): The present invention relates to the identification of modulators of G-protein coupled receptors, and the use of such modulators in the treatment of adipocyte associated conditions. G-protein coupled receptors (GPCRs) are a super-family of membrane receptors that mediate a wide variety of biological functions. Upon binding of extracellular ligands, GPCRs interact with a specific subset of heterotrimeric G proteins that can, in their activated forms, inhibit or activate various effector enzymes and/or ion channels. All GPCRs are predicted to share a common molecular architecture consisting of seven transmembrane helices linked by alternating intracellular and extracellular loops. The extracellular receptor surface has been shown to be involved in ligand binding whereas the intracellular portions are involved in G protein recognition and activation. Activation of receptors coupled to the G.sub.i family of G proteins leads to inhibition of adenylate cyclase and lowering of intracellular cAMP levels. In adipocytes this leads to inhibition of hormone-sensitive lipase (HSL) which regulates the process of lipolysis, i.e. the hydrolysis of triglycerides (TG) to glycerol and non-esterified fatty acids (NEFA). Inhibition of lipolysis and the concomitant lowering of NEFA levels cause a reduction of hepatic triglyceride synthesis resulting in a fall in the levels of TG-rich lipoproteins. This then leads to an elevation in high-density lipoprotein (HDL) levels, thus giving the desired clinical profile of high HDL and low TG for the treatment of dyslipidemia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel compositions of eprosartan Inventor(s): Venkatesh, Gopadi M.; (King of Prussia, PA) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030022928 Date filed: August 6, 2002 Abstract: This invention relates to a novel composition comprising eprosartan, or a salt, solvate, or hydrate thereof, in particulate form, a process for its production and methods of using the composition to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to novel compositions of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene-2-thiophenepropionic acid [eprosartan] or its methanesulfonate salt [eprosartan mesylatel], and to the use of such compositions in therapy to block angiotensin II (AII) receptors and in the treatment of hypertension, congestive heart failure and renal failure. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. It is known that pharmaceutically active compounds may be subjected to milling procedures to obtain a particle size appropriate for tablet formation and for other formulation types. Air jet milling and fluid energy milling (micronising) have been favoured because of the reduced risk from introducing contamination from mill materials. However, wet milling processes have been proposed for preparation of finely divided particles for pharmaceutical use, for example see U.S. Pat. No. 5,145,684. This patent discloses a wet milling procedure to produce particles of a crystalline drug substance having a surface modifier adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than about 400 nm. This particulate composition as a stable suspension is said to provide improved bioavailability for poorly water soluble compounds. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel formulations for the transdermal administration of fenoldopam Inventor(s): Crisologo, Nieves M.; (Sunnyvale, CA), van Osdol, William W.; (Mountain View, CA), Yum, Su Il; (Los Altos, CA) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040057987 Date filed: September 29, 2003 Abstract: Composition of matter for application to a body surface or membrane to administer fenoldopam by permeation through the body surface or membrane, the composition comprising fenoldopam to be administered, at a therapeutically effective rate, in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices and methods for the transdermal administration of fenoldopam for the treatment of hypertension, congestive heart failure, and chronic and acute renal failure. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/094,059, filed Jul. 24, 1998. This invention relates to sustained release formulations

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for the safe and efficacious administration of fenoldopam for, among other things, the treatment of hypertension, congestive heart failure, and acute and chronic renal failure. More particularly, the invention relates to novel methods, compositions, and devices for transdermally administering fenoldopam to a subject through a body surface or membrane over a sustained time period. The transdermal route of parenteral delivery of drugs and other biologically active agents ("agents") has been proposed for a wide variety of systemically acting and locally acting agents on either a rate-controlled or non-rate-controlled basis and is described in numerous technical publications such as the following: U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,031,894; 4,201,211; 4,286,592; 4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,573,995; 4,588,580; 4,645,502; 4,698,062; 4,704,282; 4,725,272; 4,781,924; 4,788,062; 4,816,258; 4,849,226; 4,904,475; 4,908,027; 4,917,895; 4,938,759; 4,943,435; 5,004,610; 5,071,656; 5,122,382; 5,141,750; 5,284,660; 5,314,694; 5,342,623; and 5,635,203, the disclosures of which are incorporated in their entirety herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel substituted benzimidazol-2-ones as vasopressin receptor antagonists and neuropeptide Y modulators Inventor(s): Demarest, Keith T.; (Flemington, NJ), Gunnet, Joseph W. JR.; (Flemington, NJ), Urbanski, Maud J.; (Flemington, NJ) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030073842 Date filed: October 23, 2001 Abstract: The invention is directed to substituted benzimidazol-2-ones of Formula I, 1wherein A, X, Y, m, n, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are as described in the specification, which are useful as vasopressin receptor antagonists or Neuropeptide Y Modulators for treating conditions such as aggression, obsessive-compulsive disorders, hypertension, dysmenorrhea, congestive heart failure/cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, edema, ischemia, stroke, thrombosis, water retention, nephrotic syndrome, central nervous injuries, obesity, anorexia, hyperglycemia, diabetes, anxiety, depression, asthma, memory loss, sexual dysfunction, disorders of sleep and other circadian rhythms, and Cushing's disease. Excerpt(s): This application claims priority from U.S. Ser. No. 60/243,817, filed Oct. 27, 2000. This invention relates to novel substituted benzimidazol-2-ones. More particularly, the compounds of the present invention modulate the binding of the peptide hormone vasopressin and neuropeptide Y to their respective receptors and are therefore useful for treating conditions involving increased vascular resistance, cardiac insufficiency, and disorders of energy metabolism. Vasopressin is a nonapeptide hormone that is secreted primarily from the posterior pituitary gland. The hormone effects its actions through the vascular V-1 and renal V-2 receptor subtypes. The functions of vasopressin include contraction of uterine, bladder, and smooth muscle; stimulation of glycogen breakdown in the liver; induction of platelet aggregation; release of corticotropin from the anterior pituitary and stimulation of renal water reabsorption. As a neurotransmitter within the central nervous system (CNS), vasopressin can affect aggressive behavior, sexual behavior, the stress response, social behavior and memory. The V-1a receptor mediates central nervous system effects, contraction of smooth muscle and hepatic glycogenolytic

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effects of vasopressin, while the V-1b receptor mediates anterior pituitary effects of vasopressin. The V-2 receptor, presumably found only in the kidney, effects the antidiuretic actions of vasopressin via stimulation of adenylate cyclase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Phenylethylamines and condensed rings variants as prodrugs of catecholamines, and their use Inventor(s): Dijkstra, Durk; (Bedum, NL), Venhuis, Bastiaan Johan; (Groningen, NL), Wikstrom, Hakan; (Groningen, NL) Correspondence: Mcdermott Will & Emery; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20030087948 Date filed: October 18, 2002 Abstract: Compounds of the general formula I 1wherein rings B, C, D and E may be present or not and, when present, are combined with A as A+C, A+E, A+B+C, A+B+D, A+B+E, A+C+E, A+B+C+D or A+B+C+D+E, rings B, C and E being aliphatic whereas ring D may be aliphatic or aromatic/hetero-aromatic, and wherein X is -(CH.sub.2).sub.m--, in which m is an integer 1-3, to form a ring E or, when E is absent, a group R.sub.1 bound to the nitrogen atom, wherein R.sub.1 is selected from the group consisting of a hydrogen atom, alkyl or haloalkyl groups of 1 to 3 carbon atoms, cycloalkyl(alkyl) groups of 3 to 5 carbon atoms (i.e. including cyclopropyl, cyclopropylmethyl, cyclobutyl and cyclobutylmethyl) and wherein Y is -(CH.sub.2).sub.n--, in which n is an integer 1-3, to form a ring C or when C is absent, a group R.sub.2 bound to the nitrogen atom, wherein R.sub.2 is selected from the group consisting of a hydrogen atom, alkyl or haloalkyl groups of 1 to 7 carbon atoms, cycloalkyl(alkyl) groups of 3 to 7 carbon atoms, alkenyl or alkylnyl groups of 3 to 6 carbon atoms, arylalkyl, heteroarylalkyl having 1 to 3 carbon atoms in the alkyl moiety, whilst the aryl/heteroaryl nucleus may be substituted, provided that when rings B, C, D and E are absent NR.sub.1R.sub.2 is different from dimethylamino, N-methyl-Nethylamino, N-methyl-N-propynyl-amino, N-methyl-N-propylamino and Nhydroxipropyl-N-methylamino, and salts thereof with pharmaceutically acceptable acids or bases are disclosed as well as the use of such compounds for the manufacturing of pharmaceutical compositions for the treatment of Parkinson's disease, psychoses, Huntington's disease, impotence, renal failure, heart failure or hypertension, such pharmaceutical compositions and methods of treating Parkinson's disease and schizophrenia. Excerpt(s): The present invention relates to new chemical compounds representing a new prodrug principle for the generation of catecholamines, in particular catecholethylamines, to processes for their preparation, pharmaceutical compositions containing them and their use in therapy. Neurodegenerative diseases are becoming more prevalent with the aging population. One particular neurodegenerative disease which typically has its onset between the ages of 50 and 80 years of age is Parkinson's disease. Parkinson's disease is a disorder of the brain which is characterized by tremor and difficulty with walking, movement, and coordination. Parkinson's disease appears to be caused by a progressive deterioration of dopamine-containing neurons in the substantial nigra zona compacta of the brain. Dopamine is a chemical neurotransmitter which is utilized by brain cells to transmit impulses to control or modulate peripheral muscle movement. The loss of the dopamine-containing neurons results in reduced

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amounts of dopamine available to the body. Insufficient dopamine is thought to disturb the balance between dopamine and other neurotransmitters such as acetylcholine. When such dopamine levels are reduced, nerve cells cannot properly transmit impulses, resulting in a loss of muscle control and function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Phosphate transport inhibitors Inventor(s): Gaitanopoulos, Dimitri; (King of Prussia, PA), Girard, Gerald; (King of Prussia, PA), Weinstock, Joseph; (King of Prussia, PA) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030216449 Date filed: November 8, 2002 Abstract: N-Aryl-2-sulfonamidobenzamides, useful for treatment of chronic renal failure and uremic bone disease, are disclosed. Excerpt(s): The present invention involves the treatment of chronic renal failure, uremic bone disease and related diseases by inhibition of phosphate retention by certain N-aryl2-sulfonamidobenzamides. When kidneys are injured, the adaptive mechanisms involved in restoring homeostasis can lead to additional injury and an inexorable progression to end stage renal disease (ESRD) (Hostetter et al, Am. J. Physiol. 241:F85F93 (1981)). ESRD affects more than 270,000 patients in the US. While the use of dialysis and kidney transplantation have dramatically improved the survival rate of patients with ESRD, a number of problems have appeared in these patients which complicates their long term management. Early and major contributors to the morbidity of patients with ESRD are abnormalities in mineral and bone metabolism induced by a progressive loss of renal excretory function. Among other factors, phosphate (Pi) retention has been identified as playing a major role in the progression of renal failure and in the generation of secondary hyperparathyroidism (HPTH) and uremic bone disease. Evidence implicating a role for Pi retention in the progression of chronic renal failure (CRF) has come mainly from studies on experimental animals. Ibels et al, N. Engl. J. Med. 298:122-126, (1978), first demonstrated in a rat model of CRF that dietary Pi restriction prevented renal functional deterioration as assessed by stabilization or improvement of serum creatinine levels, reduced proteinuria, improved histology and reduced mortality. Similar findings were obtained in a rat model of nephrotoxic serum nephritis (Karlinsky et al, Kidney Int. 17:293-302 (1980)). However, these studies were criticized on the basis that a low Pi diet is associated with decreased food intake and thus protein intake which by itself can reduce the progression of CRF. Therefore, Lumlertgul et al, Kidney Int. 29:658-666, (1986) placed 5/6th nephrectomized rats on a normal Pi diet but gave one group a Pi binder. All rats were pair fed and had similar caloric, protein, carbohydrate, vitamin and mineral intakes. At both 6 and 12 weeks rats ingesting the Pi binder showed a lower protein excretion, lower serum creatinine level, lower renal calcium content and less histologic scarring than rats not receiving the Pi binder. This study demonstrated unequivocally that dietary Pi restriction can have beneficial effects on the progression of CRF independent of caloric and protein intake in experimental animals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Physiologically active polypeptide and DNA Inventor(s): Izumi, Atsushi; (Tokyo, JP), Kangawa, Kenji; (Miyazaki, JP), Maekawa, Keiji; (Tokyo, JP), Matsuo, Hisayuki; (Hyogo, JP), Minamino, Naoto; (Miyazaki, JP), Sudoh, Tetsuji; (Tokyo, JP), Takashima, Mika; (Tokyo, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030162710 Date filed: January 3, 2003 Abstract: A physiologically active polypeptide derived from human brain and a DNA fragment comprising the base sequence encoding the polypeptide are disclosed. The polypeptide possesses excellent smooth muscle relaxation activity, diuretic or natriuretic activity, and vasodepressor activity, and is thus useful as a medicine for curing circulation diseases, e.g. cardiac edema, nephric edema, hepatic edema, pulmonary edema, hypertension, congestive heat failure, and acute and chronic renal failure. Excerpt(s): This invention relates to a physiologically active polypeptide, a DNA encoding the polypeptide, and a pharmaceutical composition for treating and curing circulation diseases comprising the polypeptide as an effective ingredient. Structures of new polypeptides secreted by human or rat artium and having natriuretic activity have successively been determined and reported in the years 1983-1884 [Biochem. Biophys. Res. Commun. 117, 859 (1983); Biochem. Biophys. Res. Commun. 118, 131-139 (1984)]. These polypeptides were named artium natriuretic peptides (hereinafter referred to as "ANP"). Since they have strong natriuretic activity as well as relaxing activity of vessel and smooth muscle, they are attracting much attention as a new peptide medicine for circulation disease. In 1988, a new peptide having diuretic activity was isolated in a purified form from porcine brain. Its structure was determined and the peptide was named "porcine brain natriuretic peptide" (hereinafter referred to as porcine BNP or pBNP) [Nature, 332, No. 6159, 78-81 (1988); Biochem. Biophys. Res. Commun. 155, 726732 (1988)]. Pharmaceutical activities of pBNP resemble those of ANP, and include diuretic activity, natriuretic activity, vasodepressor activity, chicken rectum relaxation activity, and the like. The specific activities of pBNP also resemble those of ANP, except that the rectum relaxation activity of pBNP is 3 to 4 times higher than that of ANP. This is the reason that pBNP is expected to be a new medicine for circulation disease and that studies involving DNA of porcine BNP are being undertaken. Cloning of cDNA possessing a base sequence encoding porcine BNP and its precursor has been reported [Biochem. Biophys. Res. Commun. 157 (1), 410-416 (1988)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pyrazole compositions Inventor(s): Banks, Bernard Joseph; (Sandwich, GB), Eshelby, James John; (Sandwich, GB), Logan, Nathan Anthony; (Sandwich, GB), Schulz, Darren John; (Sandwich, GB) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030232848 Date filed: April 2, 2003

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Abstract: Compounds of formulae (IA) and (IB): 1wherein R.sup.1, R.sup.2, R.sup.3, Ar.sup.1 and X are as defined above, are endothelin antagonists. The compounds are therefore useful in the treatment of a variety of conditions mediated by endothelin, such as restenosis, renal failure and systemic and pulmonary hypertension. Excerpt(s): This invention relates to pyrazole derivatives useful in the treatment of a variety of conditions mediated by endothelin and to pharmaceutical formulations containing such compounds useful for the treatment of humans and non-human mammals. Endothelin (ET) is a potent vasoconstrictor synthesised and released by endothelial cells. There are three distinct isoforms of ET: ET-1, ET-2 and ET-3, all being 21-amino acid peptides and herein the term `endothelin` refers to any or all of the isoforms. Two receptor subtypes, ET.sub.A and ET.sub.B have been pharmacologically defined (see for example H. Arai et al., Nature, 348, 730, 1990) and further subtypes have recently been reported. Stimulation of ET.sub.A promotes vasoconstriction and stimulation of ET.sub.B receptors causes either vasodilation or vasoconstriction. The main effects of ET are observed in the cardiovascular system, particularly in the coronary, renal, cerebral and mesenteric circulation, and the effects of endothelin are often long-lasting. Stimulation of ET receptors also mediate further biological responses in cardiovascular and non-cardiovascular tissues such as cell proliferation and matrix formation. Increased circulating levels of endothelin have been observed in patients who have undergone percutaneous transluminal coronary angioplasty (PTCA) (A. Tahara et al., Metab. Clin. Exp. 40, 1235, 1991) and ET-1 has been found to induce neointimal formation in rats after balloon angioplasty (S. Douglas et al., J. Cardiovasc. Pharm., 22 (Suppl 8), 371, 1993). The same workers have found that an endothelin antagonist, SB209670, causes a 50% reduction in neointimal formation relative to control animals (S. Douglas et al., Circ Res, 75, 1994). Antagonists of the endothelin receptor may thus be useful in preventing restenosis post PTCA. The ET.sub.A/B receptor antagonist Bosentan reportedly decreased blood pressure in hypertensive patients (H. Krum et al., New Eng. J. Med. (1998) 338, 784-790). Antagonists of ET.sub.B receptors such as BQ-788 have been demonstrated to increase peripheral resistance in man (Hypertension (1999) 33, 581-585). Thus ET.sub.A-selective receptor antagonists are most likely to be of benefit in hypertension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Quinoline derivatives Inventor(s): Mueller, Werner; (Aesch, CH), Neidhart, Werner; (Hagenthal le Bas, FR), Pflieger, Philippe; (Schwoben, FR), Plancher, Jean-Marc; (Knoeringue, FR) Correspondence: Hoffmann-la Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20020198194 Date filed: May 20, 2002 Abstract: Quinoline derivatives are useful as neuropeptide Y (NPY) receptor ligands and are particularly effective as neuropeptide Y (NPY) antagonists. These compounds are useful in pharmaceutical preparations for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders, or obesity. Excerpt(s): The present invention is concerned with novel quinoline derivatives useful as neuropeptide Y (NPY) receptor ligands, particularly neuropeptide Y (NPY) antagonists. and pharmaceutically acceptable salts or esters thereof. A preferred

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embodiment is where R.sup.1 is hydrogen, alkyl, alkoxyalkyl, alkenyl, alkinyl, hydroxyalkyl, aralkyl, heterocyclylalkyl, cycloalkylalkyl, NH.sub.2--SO.sub.2--, monoalkylamino-SO.sub.2--, dialkylamino-SO.sub.2--, or alkyl-SO.sub.2--; R.sup.4 is hydrogen, alkyl, alkoxy, hydroxy, NH.sub.2--, monoalkylamino, dialkylamino, acetylamino, or cyano; R.sup.5 is hydrogen; and A is a saturated ring consisting of the nitrogen atom which is attached to the quinoline ring and a --(CH.sub.2).sub.n-- moiety with n being 4, 5, or 6. Preferred compounds are where R.sup.1 is hydrogen, cycloalkylalkyl, aralkyl, or heteroarylalkyl. Further preferred compounds are where R.sup.1 is hydrogen, aralkyl or heteroarylalkyl, favorably hydrogen, phenylalkyl, pyridinylalkyl, phenylalkyl wherein the phenyl cycle is substituted by one to three substituents independently selected from the group consisting of alkoxy, cyano and halogen, and pyridinylalkyl wherein the pyridinyl cycle is substituted by one to three substituents independently selected from the group consisting of alkoxy, cyano and halogen. Especially preferred is where R.sup.1 is hydrogen, cyclopropylmethyl, (methoxyphenyl) methyl, (cyanophenyl) methyl, (chlorophenyl) methyl, pyridinylmethyl, chloropyridinylmethyl, or fluoropyridinylmethyl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Renal nerve stimulation method and apparatus for treatment of patients Inventor(s): Gelfand, Mark; (New York, NY), Levin, Howard R.; (Teaneck, NJ) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030216792 Date filed: April 8, 2003 Abstract: A method and apparatus for treatment of heart failure, hypertension and renal failure by stimulating the renal nerve. The goal of therapy is to reduce sympathetic activity of the renal nerve. Therapy is accomplished by at least partially blocking the nerve with drug infusion or electrostimulation. Apparatus can be permanently implanted or catheter based. Excerpt(s): This application is related and claims priority to the following commonlyowned provisional applications: Serial No. 60/370,190, entitled "Modulation Of Renal Nerve To Treat CHF", that was filed in the U.S. Patent and Trademark Office (USPTO) on Apr. 8, 2002; Serial No. 60/415,575 entitled "Modulation Of Renal Nerve To Treat CHF", that was filed in the USPTO on Oct. 3, 2002, and Serial No. 60/442,970 entitled "Treatment Of Renal Failure And Hypertension", that was filed in the USPTO on Jan. 29, 2003. The entirety of each of these provisional applications is incorporated by reference herein. This invention relates to methods and apparatus for treatment of congestive heart failure, chronic renal failure and hypertension by nerve stimulation. In particular, the invention relates to the improvement of these conditions of patients by blocking signals to the renal (kidney) nerve. Congestive Heart Failure (CHF) is a form of heart disease still increasing in frequency. According to the American Heart Association, CHF is the "Disease of the Next Millennium". The number of patients with CHF is expected to grow even more significantly as an increasing number of the "Baby Boomers" reach 50 years of age. CHF is a condition that occurs when the heart becomes damaged and reduces blood flow to the organs of the body. If blood flow decreases sufficiently, kidney function becomes impaired and results in fluid retention, abnormal hormone secretions and increased constriction of blood vessels. These results increase the workload of the heart and further decrease the capacity of the heart to pump blood

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through the kidney and circulatory system. This reduced capacity further reduces blood flow to the kidney, which in turn further reduces the capacity of the blood. It is believed that the progressively-decreasing perfusion of the kidney is the principal non-cardiac cause perpetuating the downward spiral of the "Vicious Cycle of CHF". Moreover, the fluid overload and associated clinical symptoms resulting from these physiologic changes are predominant causes for excessive hospital admissions, terrible quality of life and overwhelming costs to the health care system due to CHF. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic agent for renal failure Inventor(s): Kurumatani, Hajimu; (Kanagawa, JP), Suzuki, Motohiro; (Kanagawa, JP) Correspondence: Schnader Harrison Segal & Lewis, Llp; 1600 Market Street; Suite 3600; Philadelphia; PA; 19103 Patent Application Number: 20030092760 Date filed: November 7, 2002 Abstract: The present invention relates to a therapeutic agent for renal failure comprising, as an active ingredient, a 4,8-inter-m-phenylene prostaglandin I.sub.2 derivative, and also relates to a method of treatment of renal failure using the same. Excerpt(s): The present invention relates to a therapeutic agent for renal failure comprising, as an active ingredient, a 4,8-inter-m-phenylene prostaglandin I.sub.2 derivative or a pharmacologically acceptable salt thereof. Prostaglandins (PGs) are a class of naturally occurring compounds with a wide variety of physiological activities, which have a common prostanoic acid skeleton. Naturally occurring PGs are classified into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PGJs according to the structural characteristics of the 5-membered ring in the skeleton. It is and also classified into subclasses 1, 2, 3 and so on according to the ansaturation and oxidation. Various synthetic analogues of these PGs are known. Among these, PGI.sub.2, which is a typical PGI derivative, is called prostacycline (see Nature, vol. 268, p. 688, 1976). PGI.sub.2 is known as a substance having potent platelet aggregation inhibiting activity and peripheral vasodilator activity. Japanese Examined Patent Application Publication Nos. 2-12226, 2-57548 and 1-53672 have described 4,8-inter-m-phenylene PGI.sub.2 derivatives, in which the exo-enol ether moiety that is a structurally characteristic portion of PGI.sub.2 is converted to an inter-m-phenylene moiety to substantially improve the instability of PGI.sub.2. However, it has not yet recognized that such derivatives have therapeutic activities on renal failure. Renal failure is a condition characterized by decreased number of functional nephrons, resulting in reduced excretion of nitrogenous metabolic products and eventually causing the failure to maintain homeostasis in the biological environment. Specifically, this can be said to be a condition in which blood urea nitrogen (BUN) and creatinine levels are continuously increased. Renal failure is categorized into two primary types: acute renal failure in which the onset is abrupt and recovery may occur; and chronic renal failure which is slowly progressive but irreversible. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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THIAZOLE DERIVATIVES Inventor(s): Mattei, Patrizio; (Riehen, CH), Neidhart, Werner; (Hagenthal le Bas, FR), Nettekoven, Matthias Heinrich; (Grenzach-Wyhlen, DE), Pflieger, Philippe; (Schwoben, FR), Taylor, Sven; (Riedisheim, FR) Correspondence: Hoffmann-la Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20030225141 Date filed: February 26, 2003 Abstract: Compounds of formula I are provided 1as well as pharmaceutically acceptable salts and esters thereof, wherein R.sup.1 to R.sup.5, n, m and A have the significance disclosed in the specification, and can be used for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders and obesity. Excerpt(s): Neuropeptide Y is a 36 amino acid peptide that is widely distributed in the central and peripheral nervous systems. This peptide mediates a number of physiological effects through its various receptor subtypes. Studies in animals have shown that neuropeptide Y is a powerful stimulus of food intake, and it has been demonstrated that activation of neuropeptide Y Y5 receptors results in hyperphagia and decreased thermogenesis. Therefore compounds that antagonize neuropeptide Y at the Y5 receptor subtype represent an approach to the treatment of eating disorders such as obesity and hyperphagia. The current approach is aiming at medical intervention to induce weight loss or prevention of weight gain. This is achieved by interfering with appetite control, which is mediated by the Hypothalamus, an important brain region proven to control food intake. Herein, neuropeptide Y (NPY) has been proven to be one of the strongest central mediators of food intake in several animal species. Increased NPY levels result in profound food intake. Various receptors of neuropeptide Y (NPY) have been described to play a role in appetite control and weight gain. Interference with these receptors is likely to reduce appetite and consequently weight gain. Reduction and long-term maintenance of body weight can also have beneficial consequences on con associated risk factors such as arthritis, cardiovascular diseases, diabetes and renal failure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment or prevention of acute renal failure Inventor(s): Moskowitz, David W.; (St. Louis, MO) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20030032650 Date filed: August 8, 2002 Abstract: Adenosine receptor antagonists, especially aminophyllline, are used to treat or prevent acute renal failure. In the preferred embodiment, aminophylline is administered by infusion so that it does not exceed a serum theophylline level of 15-20 micrograms/ml, most preferably the aminophylline is administered to achieve a serum theophylline concentration of 3-10 micrograms/ml, with an infusion rate of 0.1-0.6 mg/kg IBW/hour (IBW=ideal body weight). The adenosine receptor antagonist can also be used to help sustain a kidney for transplant purposes. Preferably, aminophylline is

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loaded while the kidney is still part of the donor. A dose of aminophylline of 5 mg/kg lean body weight is infused into the donor over a 30-60 min period, with cardiac monitoring. The infusion dose is decreased in the event of supraventricular or ventricular tachycardias. The kidney is removed and placed in the standard "cold" bath, but containing aminophylline at a dose of 5-10 micrograms/ml (5-10 mg/l). The kidney is then transported to the recipient. The recipient is similarly preloaded with 5 mg/kg lean body mass aminophylline intravenously over 30-60 min with cardiac monitoring, with a constant infusion of 0.1-0.3 mg/kg lean body mass/hr continuing during the next 24 hours after the kidney is transplanted into the recipient. Excerpt(s): This application claims priority to U.S. S. No. 60/310,686 filed Aug. 8, 2001 and U.S. S. No. 60/352,075 filed Jan. 28, 2002. This is generally in the field of treatment or prevention of acute renal failure due to prerenal causes by administration of an antagonist of adenosine signaling, such as aminophylline, and of treatment of kidney transplants (renal allografts) to prolong survival of the graft during cold ischemia and immediately after transplantation. Acute kidney failure occurs when illness, infection, or injury damages the kidneys resulting in a rapid decline in the kidneys' ability to clear the blood of toxic substances. Temporarily, the kidneys cannot adequately remove fluids and wastes from the body or maintain the proper level of certain kidney-regulated chemicals leading to an accumulation of metabolic waste products, such as urea, in the blood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of des-Aspartate-angiotensin I as an agent for the treatment and prevention of glomerulosclerosis and renal failure Inventor(s): Sim, Meng Kwoon; (Singapore, SG), Tan, Chorh Chuan; (Singapore, SG) Correspondence: Klarquist Sparkman, Llp; One World Trade Center, Suite 1600; 121 S.W. Salmon Street; Portland; OR; 97204; US Patent Application Number: 20030086920 Date filed: October 11, 2002 Excerpt(s): The present invention relates generally to a method for the treatment and/or prophylaxis of renal-related disorders. More particularly, the present invention contemplates a method for the treatment and/or prophylaxis of glomerulosclerosis and/or end stage renal failure and/or related conditions. The method of the present invention is preferably practised by the administration of a derivative of angiotensin I. Generally, but not exclusively, the angiotensin I derivative exhibits anti-angiotensin II properties. In a preferred embodiment, the angiotensin I is des-Aspartate-angiotensin I or a derivative, homologue or analogue thereof. The present invention further contemplates compositions for use in the treatment and/or prophylaxis of renal-related disorders such as but not limited to glomerulosclerosis and/or end stage renal failure. Renal failure and other renal related conditions contribute to significant morbidity and mortality in patients affected by such conditions. There is a need, therefore, to develop more efficacious pharmaceutical molecules useful in the treatment of renal conditions. des-Aspartate angiotensin I (des-Asp-angiotensin I) is a nonapeptide produced from a decapeptide by the action of an aminopeptidase. The nonapeptide is produced from angiotensin I by enzymatic NH.sub.2-terminal degradation (1). des-Asp-angiotensin I is a substrate for plasma and pulmonary angiotensin converting enzyme (2). Furthermore, des-Asp-angiotensin I acts on a specific indomethacin-sensitive subtype of angiotensin receptor (3) and to antagonize the pressor (4) and hypertrophic (5) actions of angiotensin

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II. Angiotensin II is a key mediator of glomerulosclerosis in progressive kidney diseases (6-8). In work leading up to the present invention, the inventors determined that the anti-angiotensin II properties of des-Asp-angiotensin I can be exploited in the treatment and/or prophylaxis of renal-related disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of propargyl glycine amino propargyl diol compounds for treatment of renal failure Inventor(s): Baran, John S.; (Winnetka, IL), Hanson, Gunnar J.; (Skokie, IL) Correspondence: Pharmacia Corporation; Corporate Patent Department; 800 North Lindbergh - 04e; ST. Louis; MO; 63167; US Patent Application Number: 20030144542 Date filed: November 28, 2001 Abstract: Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I 1wherein A is selected from CO and SO.sub.2 wherein X is selected from oxygen atom and methylene; wherein each of R.sub.1 and R.sub.9 is a group independently selected from hydrido, methyl, ethyl, npropyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R.sub.1 and R.sub.9 are attached may be combined with oxygen to form an N-oxide; wherein R.sub.2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R.sub.3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2pyridylethyl; wherein each of R.sub.5 and R.sub.8 is independently propargyl or a propargyl-containing moiety; wherein R.sub.7 is cyclohexylmethyl; wherein each of R.sub.4 and R.sub.6 is independently selected from hydrido and methyl; wherein each of R.sub.11 and R.sub.12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 07/784,272 filed Oct. 29, 1991. Renin-inhibiting compounds are known for control of hypertension. Of particular interest herein are compounds useful as renin inhibiting agents. Renin is a proteolytic enzyme produced and secreted into the bloodstream by the juxtaglomerular cells of the kidney. In the bloodstream, renin cleaves a peptide bond in the serum protein angiotensinogen to produce a decapeptide known as angiotensin I. A second enzyme known as angiotensin converting enzyme, cleaves angiotensin I to produce the octapeptide known as angiotensin II. Angiotensin II is a potent pressor agent responsible for vasoconstriction and elevation of cardiovascular pressure. Attempts have been made to control hypertension by blocking the action of renin or by blocking the formation of angiotensin II in the body with inhibitors of angiotensin I converting enzyme. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with renal failure, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “renal failure” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on renal failure. You can also use this procedure to view pending patent applications concerning renal failure. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON RENAL FAILURE Overview This chapter provides bibliographic book references relating to renal failure. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on renal failure include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “renal failure” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on renal failure: •

Clinical Practice Guidelines for the Treatment of Anemia of Chronic Renal Failure Source: New York, NY: National Kidney Foundation. 1997. 174 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Fax (212) 689-9261. PRICE: $13.00. ISBN: 0962972177. Summary: In March 1995, the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) was established, with the objective of improving patient outcomes and survival by providing recommendations for optimal clinical practices in four areas: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and the treatment of anemia of chronic renal failure (CRF). This document presents 28 clinical practice guidelines for anemia. They are categorized in seven sections: anemia workup, target hematocrit and hemoglobin, iron support, administration of Epoetin (erythropoietin), inadequate epoetin response, the role of red blood cell transfusions, and possible adverse effects related to epoetin therapy. Each guideline is accompanied

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by a rationale, enabling dialysis caregivers to make informed decisions about the proper care plan for each individual patient. This document also includes a list of acronyms and abbreviations, a description of the guideline development methodology, endnotes, references, biographical sketches of the NKF-DOQI anemia work group members, and a complete listing of the articles reviewed by the anemia work group. 1 figure. 9 tables. 349 references. (AA-M). •

Kidney Failure and the Federal Government Source: Washington, DC: National Academy Press. 1991. 426 p. Contact: Available from National Academy Press. 2101 Constitution Avenue, NW, Washington, DC 20055. (800) 624-6242. PRICE: $39.96 plus shipping and handling. ISBN: 0309044324. Summary: In the Social Security Amendments of 1972, Congress created an entitlement to Medicare for all persons with a diagnosis of permanent kidney failure who were fully or currently insured or eligible for benefits under Social Security, and for spouses or dependent children of such persons. The ESRD program is unique within Medicare in that it is the only case in which the diagnosis of a categorical disease provides the basis for an entitlement for persons of all ages. This book is the report of the Institute of Medicine (IOM), which was asked by Congress in 1987 to study the ESRD program with respect to the following issues: epidemiological and demographic factors that may affect access to treatment, quality of care, or the resource requirements of the program; access to treatment; quality of care; effect of reimbursement on quality of care; and the adequacy of existing data systems to monitor these factors. The book includes five sections. Part I is an overview of the study and the ESRD program. Part II deals with patients and providers, including the results of patient focus groups, ethical issues related to the initiation and termination of treatment and the problem patient, background information about the patient population, special ESRD groups (pediatric, elderly, diabetic, hypertensive, ethnic groups), and the nature and structure of dialysis and transplantation providers. Part III deals with access issues, including access to transplantation. Part IV addresses the relationship between reimbursement and quality, and Part V focuses on data and research. The conclusions and recommendations of the IOM committee are provided in each section. The book includes extensive appendices, including a glossary, a list of acronyms and initialisms, commissioned papers and contractor reports, survival analysis methods, IOM committee public hearings reports and workshop reports, and a list of the IOM patient focus group participants. A subject index concludes the volume. 17 figures. 64 tables.

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Renal Failure: Blackwell's Basics of Medicine Source: Oxford, England: Blackwell Science Ltd. 1995. 295 p. Contact: Available from Blackwell Science, Inc. 238 Main Street, Cambridge, MA 02142. (800) 215-1000 or (617) 876-7000. Fax (617) 492-5263. PRICE: $24.95. ISBN: 0865424306. Summary: This book for health professionals on renal failure is from a series that examines relevant topics in medicine using concepts that pertain to the basic sciences. In this series, readers learn to interpret clinical data based on pathophysiological concepts. Four sections in this book cover the following issues: essentials, pathophysiology, clinical picture, and management of renal failure. Each section offers questions, with answers of one or two paragraphs on relevant topics. The 555 questions are numbered for ease of access through the subject index. Specific topics covered include: the anatomy of the kidneys, the kidney function tests used for diagnosis and monitoring, electrolyte

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function, urine concentration and dilution, oral water load, the roles of aldosterone, the role of the kidney in acid base balance, potassium, dietary therapy, chronic renal failure, polyuria, water and salt homeostasis, metabolic acidosis, renal tubular acidosis, hyperkalemia, acute tubular necrosis, uremia, renal impairment associated with diabetes mellitus, etiology of renal failure, hepatorenal syndrome, obstructive uropathy, anemia and erythropoietin, osteodystrophy, dialysis, prognosis, cost factors, and kidney transplantation. •

Pathogenetic and Therapeutic Aspects of Chronic Renal Failure Source: New York, NY: Marcel Dekker, Inc. 1997. 242 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. PRICE: $115.00. ISBN: 0824798945. Summary: This book is based on an international workshop, Chronic Renal Failure: Pathogenetic and Therapeutic Aspects, held in Berlin in May 1996. The first part of the book deals with arterial hypertension, hyperlipidemia, and metabolic acidosis as factors that accelerate the progression of chronic renal failure (CRF) and with the effect of dietary protein restriction as a measure to slow the advance of renal insufficiency. The second part addresses the etiology and pathophysiology of myocardial hypertrophy in general, and especially in uremia, and the influence of the dialysis regimen on the development of myocardial hypertrophy. The final section discusses the correction of renal anemia via treatment with recombinant human erythropoietin (rhEPO), with special emphasis on its effects on cardiac function and hypertrophy and on the function of parts of the endocrine system. Also included are an analysis of the use of rhEPO in renal transplant patients and an overview of the problems of iron supplementation in rhEPO treatment. The 17 chapters, each written by experts in the field, include reference lists; a subject index concludes the book.

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Coping with Kidney Failure Source: Garden City Park, NY: Avery Publishing Group. 1987. 309 p. Contact: Available from Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757 or (516) 741-2155. Fax (516) 742-1892. E-mail: [email protected]. Website: www.averypublishing.com. PRICE: $14.95 plus shipping and handling. ISBN: 0895293706. Summary: This book offers people with kidney disease a guide to adapting to life with kidney failure. The first part of the book presents background information on kidney failure: what it is, some of the causes of kidney failure, diagnostic considerations, symptoms and signs of kidney failure, and prevention and treatment strategies. The other main parts deal with different aspects of living with kidney failure, including kidney transplantation, dialysis (both hemodialysis and peritoneal dialysis), coping with emotions, changes in general lifestyle, and living with others. Specific chapters are offered on the child and adolescent with kidney failure. The author cautions that even if medical treatment is successful, both dialysis and transplantation can be psychologically debilitating and can cause considerable emotional difficulty. Suggestions for strategies and techniques to try are offered in the areas of diet, medications, dialysis equipment and supplies, physical changes, exercise, weight changes, nutritional needs, pain, financial problems, traveling, sexuality, dealing with family members, pregnancy, emotions, stress management. Throughout the book, the author offers vignettes of patients with kidney failure who have struggled with different issues and explains how

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they coped with their own situations. The book concludes with an appendix listing a few resources and a subject index. •

Strength and Compassion in Kidney Failure Source: Norwell, MA: Kluwer Academic Publishers. 1998. 221 p. Contact: Available from American Association of Kidney Patients (AAKP). 100 South Ashley Drive, Suite 280, Tampa, FL 3302. (800) 749-2257 or (813) 223-7099. Fax (813) 2230001. E-mail: [email protected]. PRICE: $25.00 plus shipping and handling. ISBN: 079235236X. Summary: This book presents a collection of medical columns, short stories, and letters written to offer hope, enthusiasm, and joy to people who have a chronic illness. The author, who was faced with the progressive loss of sight and ambulation from complications of diabetes, Addison's disease, and renal failure, demonstrates through her writing how she coped and prevailed despite her condition. Medical column topics include caring for diabetic feet and skin, eating, taking medications, traveling, coping with holidays, determining whether the findings of the Diabetes Control and Complications Trial are good or bad, and understanding the physical side of diabetes. Letters and commentary present personal messages about dealing with a chronic illness.

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Kidney Failure: Coping and Feeling Your Best Source: Atlanta, GA: Pritchett and Hull Associates, Inc. 1994. 48 p. Contact: Available from Pritchett and Hull Associates, Inc. 3440 Oakcliff Road NE, Suite 110, Atlanta, GA 30340-3079. (800) 241-4925. PRICE: $9.95 plus shipping; wholesale to health care professionals $5.50 plus shipping; quantity discounts available. Summary: This easy-to-read book supports patients during the difficult time of being diagnosed with renal failure. In the book, the author discusses kidney failure in general; explains peritoneal and hemodialysis; describes diet restrictions and medications for those with chronic renal failure (CRF); tells patients how to avoid problems, how to recognize them, and what to do if they occur; gives patients concrete ways to cope with a diagnosis of CRF; and contains interactive sections on meal planning, medication administration, weight monitoring, and using a support network. Weight and medicine charts are included, as is a brief resource list. The book is illustrated with cartoon line drawings, featuring a humorous personified kidney who leads the way.

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Drug Prescribing in Renal Failure: Dosing Guidelines for Adults. 4th ed Source: Philadelphia, PA: American College of Physicians. 1999. 176 p. Contact: Available from American College of Physicians (ACP). 190 N. Independence Mall West, Philadelphia, PA 19106-1572. (800) 523-1546 or (215) 351-2600. PRICE: $21.00 for ACP members; $28.00 for nonmembers. ISBN: 0943126762. Summary: This handbook presents tables of drugs used in the treatment of renal failure. The drugs are listed by generic name in alphabetical order under subdivisions based on similarity of structure and pharmacological action (e.g., penicillins, cephalosporins, and aminoglycosides are grouped together as antibiotics). For each drug, information is included on pharmacology (percent excreted unchanged, half-life in normal people and in end-stage renal failure, percent plasma protein binding, volume of distribution, dosage adjustment for renal failure, and whether the drug is used as a supplement for

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dialysis. Major drug categories include antimicrobial agents; antihypertensive and cardiovascular agents; sedatives, hypnotics, and drugs used in psychiatry; analgesics; and miscellaneous agents. An introductory outline discusses bioavailability, body distribution, metabolism, renal excretion, pharmacokinetics, dosimetry in renal disease, renal function, acute renal failure, initial versus maintenance doses, therapeutic drug monitoring, and adverse drug reactions. A bibliography and drug index are appended. •

Acute Renal Failure: Diagnosis, Treatment, and Prevention Source: New York, NY: Marcel Dekker, Inc. 1991. 519 p. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail: [email protected]. PRICE: $165.00. ISBN: 0824782259. Summary: This medical text on the diagnosis, treatment, and prevention of acute renal failure (ARF) arose from the 1988 Symposium on Acute Renal Failure. The book presents 34 papers in 4 sections: background, pathogenesis, and diagnosis; nuclear magnetic resonance and the kidney; treatment of ARF; and prevention of ARF. Specific topics include the etiology of ARF; ARF in the tropics; ischemic ARF; animal studies of ARF; nephrotoxicity; magnetic resonance imaging (MRI); drug therapy; early transplant nonfunction; dialysis treatment of ARF in children; acquired resistance in ARF; ARF caused by ACE inhibitors; and ARF following use of radiocontrast agents. Each chapter, written by experts in the field, includes numerous charts and diagrams, as well as extensive references. A subject index concludes the volume.

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Aluminum and Renal Failure Source: Boston, MA: Kluwer Academic Publishers Group. 1990. 382 p. Contact: Available from Kluwer Academic Publishers. Order Department, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. Fax (617) 871-6528. E-mail: [email protected]. PRICE: $205.50. ISBN: 0792303474. Summary: This monograph, part of the Development in Nephrology series, deals with the various aspects of and the most recent insights into aluminum accumulation, toxicity and renal failure. Besides providing a fundamental approach to the chemistry, the analysis and metabolism of aluminum are discussed, as well as the pathophysiological mechanisms of aluminum toxicity. Experimental models are proposed and the cellular and subcellular localization of the element is illustrated. Furthermore, the book focuses on the clinical consequences of aluminum accumulation and the current methods available for diagnosis and treatment. The monograph contains the most recent material on the pharmacokinetics of desferrioxamine and its chelates. Risk factors involved in the prevention of aluminum toxicity are also described. 38 figures, 35 tables, 1,491 references. (AA-M).

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Atlas of Diseases of the Kidney. Volume 1: Disorders of Water, Electrolytes, and Acid-Base/Acute Renal Failure Source: Philadelphia, PA: Current Medicine, Inc. 1999. [336 p.]. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781) 388-8250. Fax (781) 388-8270. E-mail: [email protected]. PRICE: $75.00 plus shipping and handling. ISBN: 0632043857.

220 Renal Failure

Summary: This volume is one in a series of five in the Atlas of Diseases of the Kidney, a set that offers educational images including colored photographs, schematics, tables, and algorithms. In Volume 1, the first section covers disorders of water and sodium balance; potassium, magnesium, phosphate, and calcium metabolism; and acid base balance. The second section addresses acute renal failure (ARF), including ischemic and nephrotoxic insults and the cellular and molecular mechanisms of renal injury and repair. Diagnostic evaluation, renal histology, nutrition and support therapies including intermittent hemodialysis, peritoneal dialysis, and continuous renal replacement therapies are illustrated. Other topics include ARF in the transplanted kidney; renal injury due to environmental toxins, drugs, and contrast agents; the pathophysiology of nephrotoxic ARF; and nutrition and metabolism in ARF. Each chapter features a detailed introduction and lengthy captions for each of the illustrations and diagrams offered. A subject index for Volume 1 and a section of full color plates concludes the book. •

Treatment Methods for Kidney Failure: Hemodialysis Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 2001. 14 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301) 634-0716. E-mail: [email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available online at no charge; single copy free; bulk orders available. NIH Publication number: 014666. Summary: When the kidneys fail, harmful wastes build up in the body, the blood pressure may rise, and the body may retain excess fluid and not make enough red blood cells. When this happens, treatment is required to replace the work of the failed kidneys. Hemodialysis is the most common method used to treat advanced and permanent kidney failure. This booklet helps readers recently diagnosed with kidney failure understand hemodialysis. Topics include how hemodialysis works, adjusting to changes, getting the vascular access ready, equipment and procedures, tests to monitor how well the dialysis is working, conditions related to kidney failure and their treatments (anemia, renal osteodystrophy, itching, sleep disorders, amyloidosis), how diet can help, financial issues, and current research in this area. Medical or technical terms are defined in the text. The booklet concludes with a list of resources for additional information and a brief description of the activities of the National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 6 figures.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “renal failure” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “renal failure” (or a synonym) in their titles.

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The following is indicative of the results you might find when searching for “renal failure” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A History of the Treatment of Renal Failure by Dialysis by J. Stewart Cameron; ISBN: 0198515472; http://www.amazon.com/exec/obidos/ASIN/0198515472/icongroupinterna

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A Renal Failure Diet Manual Utilizing the Food Exchange System by Mary E. Spitzer; ISBN: 0398034664; http://www.amazon.com/exec/obidos/ASIN/0398034664/icongroupinterna

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Acute and Chronic Renal Failure (Topics in Renal Disease) by M Boulton-Jones; ISBN: 0852004206; http://www.amazon.com/exec/obidos/ASIN/0852004206/icongroupinterna

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Acute and Chronic Renal Failure (Video with Self- Test and Ce Test) by Mosby; ISBN: 0323002080; http://www.amazon.com/exec/obidos/ASIN/0323002080/icongroupinterna

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Acute and Chronic Renal Failure: Pathophysiology for Nurses by Blanchard, et al; ISBN: 1930138075; http://www.amazon.com/exec/obidos/ASIN/1930138075/icongroupinterna

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Acute renal failure; ISBN: 0443019304; http://www.amazon.com/exec/obidos/ASIN/0443019304/icongroupinterna

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Acute Renal Failure by D.J. Rainford (Editor), P. Sweny (Editor); ISBN: 1850830193; http://www.amazon.com/exec/obidos/ASIN/1850830193/icongroupinterna

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Acute Renal Failure by U. Gessler (Editor), David Seybold (Editor); ISBN: 3805535791; http://www.amazon.com/exec/obidos/ASIN/3805535791/icongroupinterna

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Acute Renal Failure by C.T. Flynn (Editor); ISBN: 0852001053; http://www.amazon.com/exec/obidos/ASIN/0852001053/icongroupinterna

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Acute Renal Failure (Contemporary Issues in Nephrology, V. 6) by Barry M. Brenner (Editor), Jay H. Stein (Editor); ISBN: 0443081166; http://www.amazon.com/exec/obidos/ASIN/0443081166/icongroupinterna

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Acute renal failure : discussions in patient management, pathophysiology, clinical diagnosis, and therapy by Edward Kuehnel; ISBN: 0874888786; http://www.amazon.com/exec/obidos/ASIN/0874888786/icongroupinterna

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Acute Renal Failure in Practice by Paul Glynne, et al; ISBN: 1860942164; http://www.amazon.com/exec/obidos/ASIN/1860942164/icongroupinterna

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Acute Renal Failure in the Critically Ill (Update in Intensive Care and Emergency Medicine, No 20) by R. Bellomo (Editor), C. Ronco (Editor); ISBN: 3540584013; http://www.amazon.com/exec/obidos/ASIN/3540584013/icongroupinterna

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Acute Renal Failure in the Intensive Therapy Unit (Current Concepts in Critical Care) by David Bihari, Guy Neild (Editor); ISBN: 0387195882; http://www.amazon.com/exec/obidos/ASIN/0387195882/icongroupinterna

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Acute Renal Failure: A Companion to Brenner and Rector's the Kidney by Bruce A. Molitoris (Editor), William F. Finn (Editor); ISBN: 0721691749; http://www.amazon.com/exec/obidos/ASIN/0721691749/icongroupinterna

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Acute Renal Failure: Correlations Between Morphology and Function by Kim Solez (Editor); ISBN: 0824719042; http://www.amazon.com/exec/obidos/ASIN/0824719042/icongroupinterna

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Acute renal failure: diagnosis and management by Robert C. Muehrcke; ISBN: 0801635772; http://www.amazon.com/exec/obidos/ASIN/0801635772/icongroupinterna

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Acute Renal Failure: Diagnosis Treatment and Prevention by Kim Solez; ISBN: 0824782259; http://www.amazon.com/exec/obidos/ASIN/0824782259/icongroupinterna

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Acute Renal Failure: New Concepts and Therapeutic Strategies by Michael S. Goligorsky (Editor), Jay H. Stein (Editor); ISBN: 0443075808; http://www.amazon.com/exec/obidos/ASIN/0443075808/icongroupinterna

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Acute Renal Failure: Pathophysiology, Prevention, and Treatment by Vittorio E. Andreucci (Editor); ISBN: 0898386276; http://www.amazon.com/exec/obidos/ASIN/0898386276/icongroupinterna

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Aluminum and Renal Failure (Developments in Nephrology, Volume 26) by Marc E. Debroe (Editor), M. E. De Broe; ISBN: 0792303474; http://www.amazon.com/exec/obidos/ASIN/0792303474/icongroupinterna

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Aluminum speciation in biological fluids : implications for patients with end stage renal failure by Glen F. van Landeghem; ISBN: 9090108017; http://www.amazon.com/exec/obidos/ASIN/9090108017/icongroupinterna

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Animal Models in Chronic Renal Failure (Contributions to Nephrology, Vol 60) by N. Gretz, M. Strauch (Editor); ISBN: 380554619X; http://www.amazon.com/exec/obidos/ASIN/380554619X/icongroupinterna

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Biochemical Aspects of Renal Failure (Renal Physiology and Biochemistry Vol 12 No 5-6) by W.G. Guder (Editor); ISBN: 3805551193; http://www.amazon.com/exec/obidos/ASIN/3805551193/icongroupinterna

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Bone and Renal Failure (Contributions to Nephrology, Vol 64) by Marc E. De Broe, Frank L. Van De Vyver (Editor); ISBN: 3805547382; http://www.amazon.com/exec/obidos/ASIN/3805547382/icongroupinterna

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Bone Disease in Renal Failure by H. H. Malluche (Editor); ISBN: 3805555067; http://www.amazon.com/exec/obidos/ASIN/3805555067/icongroupinterna

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Cardiac and Renal Failure: An Expanding Role for Ace Inhibitors by Colin T. Dollery, Louis M. Sherwood (Editor); ISBN: 0932883990; http://www.amazon.com/exec/obidos/ASIN/0932883990/icongroupinterna

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Cardiovascular Disease in End-Stage Renal Failure by Joseph Loscalzo (Editor), Gerard M. London (Editor); ISBN: 0192629875; http://www.amazon.com/exec/obidos/ASIN/0192629875/icongroupinterna

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Chronic renal failure; ISBN: 0443081417; http://www.amazon.com/exec/obidos/ASIN/0443081417/icongroupinterna

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Chronic Renal Failure by G.R.D. Catto (Editor); ISBN: 074620048X; http://www.amazon.com/exec/obidos/ASIN/074620048X/icongroupinterna

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Chronic Renal Failure by F. Santos (Editor), S. Malaga (Editor); ISBN: 380555527X; http://www.amazon.com/exec/obidos/ASIN/380555527X/icongroupinterna

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Chronic Renal Failure: Pathophysiology, Manifestations, and Management by Martin Roy First; ISBN: 087488912X; http://www.amazon.com/exec/obidos/ASIN/087488912X/icongroupinterna

Books 223

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Clinical management of chronic renal failure by John R. Curtis; ISBN: 0632006617; http://www.amazon.com/exec/obidos/ASIN/0632006617/icongroupinterna

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Clinical use of drugs in renal failure by Robert James Anderson; ISBN: 0398034001; http://www.amazon.com/exec/obidos/ASIN/0398034001/icongroupinterna

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Coping With Kidney Failure by Robert H. Phillips; ISBN: 0895293706; http://www.amazon.com/exec/obidos/ASIN/0895293706/icongroupinterna

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CRC Handbook of Animal Models of Renal Failure by Steve Ash (Editor); ISBN: 0849329752; http://www.amazon.com/exec/obidos/ASIN/0849329752/icongroupinterna

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Critical Care Focus : Renal Failure by Webster, Galley; ISBN: 0727914235; http://www.amazon.com/exec/obidos/ASIN/0727914235/icongroupinterna

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Disputed Issues in Renal Failure Therapy (Contributions to Nephrology, Vol 44) by E. Wetzels (Editor), et al; ISBN: 380553938X; http://www.amazon.com/exec/obidos/ASIN/380553938X/icongroupinterna

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Drug Prescribing in Renal Failure; ISBN: 0943126169; http://www.amazon.com/exec/obidos/ASIN/0943126169/icongroupinterna

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Drug Prescribing in Renal Failure : Dosing Guidelines for Adults by George R. Aronoff (Editor), et al; ISBN: 0943126762; http://www.amazon.com/exec/obidos/ASIN/0943126762/icongroupinterna

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Electrolytes & Acute Renal Failure by G. Eknoyan (Editor); ISBN: 3805555059; http://www.amazon.com/exec/obidos/ASIN/3805555059/icongroupinterna

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Endothelium-Dependent Vasodilation & Oxidative Stress in Chronic Renal Failure (Comprehensive Summaries of Uppsala Dissertations from the Faculty of mediciNe, 1122) by Margus Annuk; ISBN: 9155452337; http://www.amazon.com/exec/obidos/ASIN/9155452337/icongroupinterna

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End-Stage Renal Failure: Patient Pictures by Smith, Health Press; ISBN: 1899541586; http://www.amazon.com/exec/obidos/ASIN/1899541586/icongroupinterna

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Experimental and Genetic Rat Models of Chronic Renal Failure by N. Gretz, M. Strauch; ISBN: 3805554990; http://www.amazon.com/exec/obidos/ASIN/3805554990/icongroupinterna

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FRIEDMAN STRATEGY IN RENAL FAILURE (Perspectives in Nephrology and Hypertension) by EA FRIEDMAN, Eli A. Friedman (Editor); ISBN: 0471015970; http://www.amazon.com/exec/obidos/ASIN/0471015970/icongroupinterna

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Growth and Endocrine Changes in Children and Adolescents With Chronic Renal Failure (Pediatric and Adolescent Endocrinology, Vol 20) by K. Scharer (Editor); ISBN: 3805549903; http://www.amazon.com/exec/obidos/ASIN/3805549903/icongroupinterna

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High-dose urography in oliguric and anuric patients; excretion of urographic contrast media in advanced renal failure by Paul F. G. M. van Waes; ISBN: 9021920697; http://www.amazon.com/exec/obidos/ASIN/9021920697/icongroupinterna

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Hormonal and Metabolic Derangements in Renal Failure (Contributions to Nephrology, Vol 50) by A. Heidland (Editor), et al; ISBN: 3805543360; http://www.amazon.com/exec/obidos/ASIN/3805543360/icongroupinterna

224 Renal Failure

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Immunological Perspectives in Chronic Renal Failure (Contributions to Nephrology; Vol 86) by H.J. Gurland, et al; ISBN: 3805552548; http://www.amazon.com/exec/obidos/ASIN/3805552548/icongroupinterna

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Kidney Failure and the Federal Government by Richard A. Rettig, Norman G. Levinsky (Editor); ISBN: 0309044324; http://www.amazon.com/exec/obidos/ASIN/0309044324/icongroupinterna

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Kidney Failure Explained (Class Health) by Andy Stein, Janet Wild; ISBN: 1859590705; http://www.amazon.com/exec/obidos/ASIN/1859590705/icongroupinterna

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Kidney Failure Explained: Everything You Always Wanted to Know About Dialysis and Transplants But Were Afraid to Ask by Andy Stein, et al; ISBN: 1872362907; http://www.amazon.com/exec/obidos/ASIN/1872362907/icongroupinterna

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Kidney Failure: Coping & Feeling Your Best by Anna K. Hollingsworth; ISBN: 0939838370; http://www.amazon.com/exec/obidos/ASIN/0939838370/icongroupinterna

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Kidney Failure: the Facts by J. Stewart Cameron, Stewart Cameron; ISBN: 0192626434; http://www.amazon.com/exec/obidos/ASIN/0192626434/icongroupinterna

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Legal and Ethical Concerns in Treating Kidney Failure: Case Study Workbook by Eli A. Friedman (Editor); ISBN: 0792365704; http://www.amazon.com/exec/obidos/ASIN/0792365704/icongroupinterna

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Living With Renal Failure by J. Parson; ISBN: 0839112750; http://www.amazon.com/exec/obidos/ASIN/0839112750/icongroupinterna

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Living with Renal Failure by J.L. Anderton (Editor), Frank M. Parsons (Editor); ISBN: 0852001975; http://www.amazon.com/exec/obidos/ASIN/0852001975/icongroupinterna

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Long-Term Hemodialysis; The Management of the Patient With Chronic Renal Failure, by Constantine L. Hampers; ISBN: 0808908197; http://www.amazon.com/exec/obidos/ASIN/0808908197/icongroupinterna

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Low Protein Diet and Progression of Chronic Renal Failure (Contributions to Nephrology, Vol 53) by M. Strauch (Editor), et al; ISBN: 3805543646; http://www.amazon.com/exec/obidos/ASIN/3805543646/icongroupinterna

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Management and Resource Allocation in the End Stage Renal Failure Units (Project Paper) by Nicholas B. Mays; ISBN: 1855510545; http://www.amazon.com/exec/obidos/ASIN/1855510545/icongroupinterna

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Mechanisms and Clinical Management of Chronic Renal Failure by Meguid El Nahas (Editor), et al; ISBN: 0192629336; http://www.amazon.com/exec/obidos/ASIN/0192629336/icongroupinterna

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Medicare End-Stage Renal Disease (kidney failure) Program : hearing before the Subcommittee on Health of the Committee on Ways and Means, House of Representatives, One Hundred Fourth Congress, first session, April 3, 1995 (SuDoc Y 4.W 36:104-40); ISBN: 0160529077; http://www.amazon.com/exec/obidos/ASIN/0160529077/icongroupinterna

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Metabolic Disturbances in the Predialytic Phase of Chronic Renal Failure (Contributions to Nephrology, Vol 65) by R. Schmicker, et al; ISBN: 3805547390; http://www.amazon.com/exec/obidos/ASIN/3805547390/icongroupinterna

Books 225

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National High Blood Pressure Education Program (NHBPEP) Working Group report on hypertension and chronic renal failure (SuDoc HE 20.3202:H 99/16) by U.S. Dept of Health and Human Services; ISBN: B000104ZZ0; http://www.amazon.com/exec/obidos/ASIN/B000104ZZ0/icongroupinterna

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Nutritional and Pharmacological Strategies in Chronic Renal Failure (Contributions to Nephrology Vol 81) by A. Alebrtazzi (Editor), A. Albertazzi; ISBN: 3805551894; http://www.amazon.com/exec/obidos/ASIN/3805551894/icongroupinterna

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Nutritional Treatment of Chronic Renal Failure by Sergio Giovannetti (Editor), Segio Giovannetti (Editor); ISBN: 0792300866; http://www.amazon.com/exec/obidos/ASIN/0792300866/icongroupinterna

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On the progression of chronic renal failure in humans by Louis-Jean Vleming; ISBN: 9090116176; http://www.amazon.com/exec/obidos/ASIN/9090116176/icongroupinterna

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Optimal Treatment Strategies For End Stage Renal Failure by Claude Jacobs (Editor); ISBN: 0192629719; http://www.amazon.com/exec/obidos/ASIN/0192629719/icongroupinterna

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Pathogenic and Therapeutic Aspects of Chronic Renal Failure by K.M. Koch (Editor), Gunter Stein (Editor); ISBN: 0824798945; http://www.amazon.com/exec/obidos/ASIN/0824798945/icongroupinterna

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Patient care in renal failure by Joan DeLong Harrington; ISBN: 0721645283; http://www.amazon.com/exec/obidos/ASIN/0721645283/icongroupinterna

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Present Day Concepts in the Treatment of Chronic Renal Failure: Dialysis and Transplantation (Contributions to Nephrology, Vol 71) by Jules Traeger, et al; ISBN: 3805549466; http://www.amazon.com/exec/obidos/ASIN/3805549466/icongroupinterna

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Prevention of Progressive Chronic Renal Failure (Oxford Monographs on Clinical Nephrology, No 1) by A. Meguid El Nahas (Editor), et al; ISBN: 0192622374; http://www.amazon.com/exec/obidos/ASIN/0192622374/icongroupinterna

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Psychological and Physiological Aspects of Chronic Renal Failure (Contributions to Nephrology, Vol 77) by Giuseppe D'Amico, Giuliano Colasanti (Editor); ISBN: 3805550642; http://www.amazon.com/exec/obidos/ASIN/3805550642/icongroupinterna

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Psychonephrology 2: Psychological Problems in Kidney Failure and Their Treatment by Norman B. Levy; ISBN: 0306411547; http://www.amazon.com/exec/obidos/ASIN/0306411547/icongroupinterna

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Quality of Life Following Renal Failure: Psychosocial Challenges Accompanying High Technology Medicine by Hannah M. McGee (Editor), Clare Bradley (Editor); ISBN: 3718655012; http://www.amazon.com/exec/obidos/ASIN/3718655012/icongroupinterna

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Rehabilitation in chronic renal failure; ISBN: 0683015788; http://www.amazon.com/exec/obidos/ASIN/0683015788/icongroupinterna

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Renal Failure (Balckwell's Basics of Medicine) by Horacio J. Adrogue, Donald E. Wesson (Contributor); ISBN: 0865424306; http://www.amazon.com/exec/obidos/ASIN/0865424306/icongroupinterna

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Renal failure in paraplegia by Colin Richard Tribe; ISBN: 0272792802; http://www.amazon.com/exec/obidos/ASIN/0272792802/icongroupinterna

226 Renal Failure

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Renal Failure, Who Cares? by F. M. Parsons (Editor); ISBN: 0852004761; http://www.amazon.com/exec/obidos/ASIN/0852004761/icongroupinterna

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Renal Failure: Diagnosis and Treatment by J. Gary Abuelo (Editor); ISBN: 0792334388; http://www.amazon.com/exec/obidos/ASIN/0792334388/icongroupinterna

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Surgery in Chronic Renal Failure: Experiences With Dialysis and Transplant Patients, International Symposium, February 1983 by Friedrich Wilhelm Eigler, Hans Dieter Jakubowski (Editor); ISBN: 0865771553; http://www.amazon.com/exec/obidos/ASIN/0865771553/icongroupinterna

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Surgical Care of the Patient With Renal Failure by Nicholas Tilney; ISBN: 0721688500; http://www.amazon.com/exec/obidos/ASIN/0721688500/icongroupinterna

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Systemic Consequences of Renal Failure by Garabed Eknoyan (Editor), James P. Knochel (Photographer); ISBN: 0808916343; http://www.amazon.com/exec/obidos/ASIN/0808916343/icongroupinterna

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Terminal Renal Failure: Therapeutic Problems, Possibilities, and Potentials (Contributions to Nephrology, Vol 78) by Horst Klinkmann (Editor); ISBN: 3805550863; http://www.amazon.com/exec/obidos/ASIN/3805550863/icongroupinterna

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The biochemical consequences of chronic renal failure by M. R. Wills; ISBN: 0839105835; http://www.amazon.com/exec/obidos/ASIN/0839105835/icongroupinterna

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The Heart in End-Stage Renal Failure: Etiology, Symptoms and Management of Uremic Heart Disease (Contributions to Nephrology, Vol 52) by V. Wizemann, et al; ISBN: 3805543581; http://www.amazon.com/exec/obidos/ASIN/3805543581/icongroupinterna

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The Heart, Kidney and Renal Failure (Mineral and Electrolyte Metabolism, 25/2) by Natale Gaspare De Santo (Editor), Luigi Iorio (Editor); ISBN: 3805568592; http://www.amazon.com/exec/obidos/ASIN/3805568592/icongroupinterna

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The Treatment of Adult Patients with Renal Failure; ISBN: 1860160670; http://www.amazon.com/exec/obidos/ASIN/1860160670/icongroupinterna

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The Treatment of Renal Failure by G. M. Yuill; ISBN: 0719006287; http://www.amazon.com/exec/obidos/ASIN/0719006287/icongroupinterna

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The Treatment of Renal Failure by J.E. Castro; ISBN: 0852003366; http://www.amazon.com/exec/obidos/ASIN/0852003366/icongroupinterna

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Therapy and Pathophysiology of End-Stage Renal Failure (Blood Purification, Vol 13, No 3-4) by G.E. Striker (Editor), et al; ISBN: 380556130X; http://www.amazon.com/exec/obidos/ASIN/380556130X/icongroupinterna

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Understanding the causes and treatment of kidney failure by Monica O'Hara; ISBN: 0433233508; http://www.amazon.com/exec/obidos/ASIN/0433233508/icongroupinterna

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WILLS METABOLIC CONSEQUENCES OF CHRONIC RENAL FAILURE by MR WILLS; ISBN: 0471260886; http://www.amazon.com/exec/obidos/ASIN/0471260886/icongroupinterna

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You can live : your guide for living with kidney failure (SuDoc HE 22.108:K 54) by U.S. Dept of Health and Human Services; ISBN: B0001178B2; http://www.amazon.com/exec/obidos/ASIN/B0001178B2/icongroupinterna

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Chapters on Renal Failure In order to find chapters that specifically relate to renal failure, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and renal failure using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “renal failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on renal failure: •

Management of Sequelae, Voiding Dysfunction and Renal Failure Source: in Hamdy, F.C, et al. Management of Urologic Malignancies. New York, NY: Elsevier Science, Inc. 2002. p. 259-269. Contact: Available from Elsevier Science, Inc. Journal Information Center, 655 Avenue of the Americas, New York, NY 10010. (212) 633-3750. Fax (212) 633-3764. Website: www.elsevier.com. PRICE: $149.00. ISBN: 443054789. Summary: A small but significant percentage of men with prostate cancer present with or progress to a metastatic and terminal stage of the disease. After attempts to control the cancer with surgery, radiation, or hormonal therapy, the urologist must also know how to treat complications related to the progression of incurable cancer. Most commonly, these complications are bone pain and pathologic fractures related to bone metastases, urethral and ureteral obstruction with progression to renal (kidney) failure, and disseminated intravascular coagulation. Long-term complications of previous attempts at controlling the cancer through hormone therapy, radiation therapy, and surgery must also be addressed in providing care for these men. This chapter on the management of sequelae, voiding dysfunction, and renal failure associated with prostate cancer is from a reference guide to all urologic cancers; the textbook features a strong emphasis on best practice management choices. The authors of this chapter stress that because there is no known treatment capable of curing patients who are refractory to hormone therapy, treatment is aimed at preventing or minimizing they symptoms from these complications and prolonging survival where possible and desirable. A patient care algorithm is provided. 1 table. 81 references.

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Acute and Chronic Renal Failure in Children Source: in Gearhart, J.P.; Rink, R.C.; Mouriquand, P.D. Pediatric Urology. Philadelphia, PA: W.B. Saunders Company. 2001. p. 777-789. Contact: Available from Elsevier, Health Sciences Division. The Curtis Center, 625 Walnut Street, Philadelphia, PA 19106. (800) 523-1649. E-mail: [email protected]. Website: www.us.elsevierhealth.com. PRICE: $239.00 plus shipping and handling. ISBN: 072168680X. Summary: Acute renal (kidney) failure (ARF) is characterized by a reversible increase in the blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to appropriately regulate fluid and electrolyte homeostasis. Chronic renal failure (CRF) results in similar alterations in fluid and electrolyte balance, but the metabolic derangements are irreversible. This chapter, from a comprehensive textbook on pediatric urology that emphasizes the pathophysiology of various disorders, reviews the common causes of ARF and CRF and the management of renal

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failure, including renal replacement therapy (dialysis and transplantation). The author notes that the purpose of renal replacement therapy is to remove endogenous and exogenous toxins and to maintain fluid, electrolyte, and acid-base balance until renal function improves (if the patient has ARF) or until transplantation can be achieved in children who have CRF. 2 figures. 3 tables. 108 references. •

Anemia in Chronic Renal Failure Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 905-912. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: Anemia has been a known complication of renal (kidney) failure for over 160 years, but its etiology (cause) and management have been better elucidated over the past 20 years. This chapter on anemia in chronic renal failure (CRF) is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The author of this chapter discusses pathophysiology, clinical manifestations, diagnosis and differential diagnosis, treatment options, notably the use of erythropoietin (epoetin). The author concludes that the use of epoetin has been one of the most important advances in the management of the patient with CRF, yet its use is still not optimal. Not enough patients with progressive renal insufficiency are receiving epoetin for even partial correction of their anemia. The chapter is clinically focused and extensively illustrated in full color. 1 figure. 5 tables. 45 references.

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Acute Renal Failure and Dialysis Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 173-191. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: Dialysis is often necessary for the treatment of acute kidney (renal) failure. The most common indications include uremia, hyperkalemia, acidosis, fluid overload, and drug overdose. This chapter on acute renal failure and dialysis is from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. The authors of the chapter define acute renal failure (ARF) as the rapid deterioration of kidney function and note that ARF is usually reversible if diagnosed and treated early. ARF is divided into three categories: prerenal, intrarenal, and postrenal. The most common indications for acute dialysis include uremia, pulmonary edema (fluid overload in the lungs), hyperkalemia (high amounts of potassium in the blood), acidosis, neurologic changes, and drug overdoses and poisonings. Treatment options for ARF include hemodialysis, isolated ultrafiltration, peritoneal dialysis, continuous renal replacement therapy (CRRT), and charcoal hemoperfusion. The chapter concludes with a brief section discussing the use of dialysis for patients undergoing rejection of a transplanted kidney. 4 figures.

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Nutrition in Chronic Renal Failure Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 935-943. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: Diet and nutrition play an integral role in the management of individuals with renal (kidney) disease. Abnormalities associated with chronic renal disease include retention of nitrogenous metabolites, a decreased ability to regulate levels of electrolytes and water, and certain vitamin deficiencies. Dietary intake can play a crucial role in managing these abnormalities. Interest in the nutritional status of patients with renal failure has increased with the understanding that poor nutrition predicts a poor outcome. This chapter on nutrition in chronic renal (kidney) failure (CRF) is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The author of this chapter discusses malnutrition, assessment of nutritional status, nutritional guidelines, monitoring and treatment, including the use of oral supplementation, tube feeding, supplementation of dialysate fluids, and appetite stimulants and growth factors. The author concludes that indices of malnutrition are powerful predictors of mortality in end stage renal disease (ESRD). The high prevalence of protein-energy malnutrition in this group is clearly related to multiple factors encountered both before and after renal replacement therapy (dialysis) has commenced. The chapter is clinically focused and extensively illustrated in full color. 8 figures. 4 tables. 28 references.

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Bone and Mineral Metabolism in Chronic Renal Failure Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 873-885. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: Disturbances of mineral metabolism are common during the course of chronic renal disease (CRF) and lead to serious and debilitating complications unless these abnormalities are addressed and treated. This chapter on bone and mineral metabolism in CRF is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The authors of this chapter discuss definitions, the epidemiology (incidence and prevalence) of these complications, pathogenesis, clinical manifestations of renal osteodystrophy, diagnosis and differential diagnosis, and treatment strategies. The chapter is clinically focused and extensively illustrated in full color. 14 figures. 2 tables. 28 references.

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Nutrition in Patients with Chronic Renal Failure and Patients on Dialysis Source: in Nissenson, A.R., Fine, R.N., and Gentile, D.E. Clinical Dialysis. 3rd ed. Norwalk, CT: Appleton and Lange. 1995. p. 518-534. Contact: Available from Appleton and Lange. 25 Van Zant Street, East Norwalk, CT 06855. PRICE: $215.00. ISBN: 0838513794.

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Summary: For many years, dietary manipulation has been an important therapeutic intervention for patients with advanced renal disease. Nutritional factors play a role in the morbidity and mortality of these patients, as well as in their quality of life and ultimate rehabilitative potential. This chapter, from a medical text on clinical dialysis, investigates the role of nutrition in patients with chronic renal failure (CRF) and patients on dialysis. The authors first outline the syndrome of malnutrition in patients with renal failure. Next, they discuss the causes of malnutrition in renal failure, including reduced nutritional intake, intercurrent illness, dialysis losses, and uremia. The authors stress the importance of accurately assessing the nutritional status of all patients with advanced renal disease in order to identify those patients who may need nutritional intervention and to monitor the effects of any therapeutic regimen. Assessment tools include history and physical examination, dietary history, anthropometry, serum proteins, and plasma amino acids. Protein restriction in patients with CRF can slow the progression of renal failure and delay the onset of uremic symptoms and associated metabolic disturbances once glomerular filtration rate (GFR) has fallen below 15 ml per minute. When the GFR falls below 5 ml per minute, dialysis therapy is usually required. Because dialysis therapy is associated with losses of protein and amino acids, the diet should be liberalized and protein intake increased. Additional topics include vitamin therapy and other supplements, nutrition in patients treated with peritoneal dialysis (PD), and intraperitoneal dialysis. 5 tables. 153 references. (AA-M). •

Cardiovascular Disease in Chronic Renal Failure Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 887-904. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: Life expectancy with end stage renal disease (ESRD) is poor despite modern renal replacement therapy (RRT, including dialysis and transplantation). Much of the premature death of these patients, particularly in the first few years of dialysis, is attributable to cardiovascular disease, including stroke, myocardial infarction, and heart failure. This chapter on cardiovascular disease in chronic renal (kidney) failure (CRF) is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The author of this chapter discusses epidemiology (incidence and prevalence), etiology and pathogenesis, clinical manifestations, management of common cardiovascular syndromes in uremia, the effects of hemodialysis and ultrafiltration on cardiovascular function, and the management of cardiovascular risk factors. The chapter is clinically focused and extensively illustrated in full color. 15 figures. 3 tables. 32 references.

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Renal Dysfunction and Postoperative Renal Failure in Obstructive Jaundice Source: in Arroyo, V., et al, eds. Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. Malden, MA: Blackwell Science, Inc. 1999. p.7998. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781)-388-8250. Fax (781) 388-8270. E-mail: [email protected]. Website: www.blackwellscience.com. PRICE: $125.00 plus shipping and handling. ISBN: 0632043423.

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Summary: Patients with obstructive jaundice (OJ) have an increased risk for a wide array of postoperative complications, namely, bleeding, infections, poor wound healing, and kidney (renal) failure. The three major consequences of biliary obstruction: immunosuppression, malnutrition, and hemodynamic (blood flow) disturbances, are all implicated in the pathogenesis of these complications. This chapter on kidney dysfunction and postoperative kidney failure in OJ is from a textbook on ascites and renal dysfunction in liver disease. The author reviews evidence linking biliary obstruction with kidney dysfunction, emphasizing the pathogenesis (development) of this association according to the most recent experimental and clinical data. This knowledge will improve the perioperative care of patients with obstructive jaundice. The author notes that prevention of perioperative kidney dysfunction is best achieved by accurate monitoring of fluid replacement and diuresis, and avoidance of all potentially nephrotoxic drugs, particularly aminoglycoside antibiotics. Preoperative internal biliary drainage, coupled with appropriate rehydration and metabolic support, appears to be a promising adjunct for improving the condition of patients with OJ, particularly of those with severe hyperbilirubinemia, sepsis, or advanced malnutrition. 5 figures. 9 tables. 75 references. •

Clinical Evaluation and Manifestations of Chronic Renal Failure Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 857-872. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: The management of chronic renal failure (CRF) is now the dominant part of the work of a clinical nephrologist. This has come about because chronic kidney disease is easily uncovered by routine blood and urine tests and treatment for end stage renal disease (ESRD) is so successful and widely applied. Although supervision of patients receiving renal replacement therapy (RRT) is the undisputed domain of the nephrologist, care of patients with progressive renal insufficiency is as important, not least because it may be possible to delay progression or to halt a disease process. Many of the complications and long-term problems of renal failure start well before dialysis or renal transplantation are even being discussed, and there are a number of options for preventing or ameliorating these. This chapter on the clinical evaluation and manifestations of CRF is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The authors of this chapter discuss definition and incidence, the epidemiology (incidence and prevalence) of CRF, etiology and pathogenesis, clinical presentations (symptoms), the complications and consequences of CRF, the management of CRF, surgery in the patient with CRF, drug prescribing in CRF, and the management of terminal uremia. The chapter is clinically focused and extensively illustrated in full color. 4 figures. 7 tables. 26 references.

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Gastrointestinal Disease in Patients With Chronic Renal Failure Source: in Nissenson, A.R., Fine, R.N., and Gentile, D.E., eds. Clinical Dialysis. 3rd ed. Norwalk, CT: Appleton and Lange. 1995. p. 607-617. Contact: Available from Appleton and Lange. 25 Van Zant Street, P.O. Box 5630, Norwalk, CT 06856. (800) 423-1359 or (203) 838-4400. PRICE: $175.00. ISBN: 0838513794.

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Summary: This chapter from a textbook on clinical dialysis covers gastrointestinal (GI) disease in patients with chronic renal failure (CRF). Topics include the types of upper GI symptoms common in patients with CRF; the pathogenesis of uremic GI lesions and upper GI tract bleeding; specific causes of GI tract bleeding in renal failure, including angiodysplasia, peptic ulcer disease, and Kaposi's sarcoma; chronic nausea and vomiting in the dialysis patient; GI medication in the dialysis patient, including the use of antiemetic therapy and prokinetic drugs and their use in gastroparesis; the causes of lower GI bleeding, including vascular telangectasia, colonic polyps, colitis, diverticular disease, and isolated idiopathic ulceration; abdominal emergencies in the patient on continuous ambulatory peritoneal dialysis (CAPD); and pancreatic disease in dialysis patients. 5 tables. 60 references. •

Calcium, Phosphorus, and Vitamin D Metabolism in Renal Disease and Chronic Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 341-369. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors discuss calcium, phosphorus, and vitamin D metabolism in renal disease and chronic renal failure (CRF). The authors begin with a brief review of normal physiologic control of calcium and phosphorus homeostasis and normal vitamin D and parathyroid hormone metabolism. Next, they discuss the effects of the failing kidney on mineral metabolism, secondary hyperparathyroidism, hyperphosphatemia, therapeutic interventions in predialysis patients, and control of phosphate retention and secondary hyperparathyroidism in dialysis patients. The authors conclude that dietary restriction of phosphorus intake and adequate dialysis therapy form the basis for management, but are usually insufficient to bring about adequate control. Calcium-based phosphate binders and hormonal vitamin D replacement are powerful adjuncts in regulating mineral pathophysiology. Despite these maneuvers, parathyroidectomy is still occasionally required. The authors provide an algorithm for the management of hyperphosphatemia and secondary hyperparathyroidism. Additional sections discuss the implications for bone disease (renal osteodystrophy), one of the more serious complications of disordered mineral metabolism in renal failure; implications for other complications; disturbances of mineral metabolism following renal transplantation; and disturbances of mineral and vitamin D metabolism in nephrotic syndrome. 5 figures. 124 references. (AA-M).

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Anemia in Patients with Chronic Renal Failure and in Patients Undergoing Chronic Hemodialysis Source: in KT/DA (Kidney Transplant/Dialysis Association, Inc.). KT/DA Patient Handbook. 4th ed. Boston, MA: KT/DA (Kidney Transplant/Dialysis Association, Inc.). 2003. p. 131-134. Contact: Available from KT/DA (Kidney Transplant/Dialysis Association, Inc.). P.O. Box 51362 GMF, Boston, MA 02205-1362. (781) 641-4000. Email: [email protected]. Website: www.ktda.org. PRICE: Full-text available online at no charge. Summary: This chapter on anemia in patients with chronic renal (kidney) failure (CRF) and in patients undergoing chronic hemodialysis is from a book that was written to help

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kidney patients understand the forms of treatment available for their kidney disease and the impact of each form of treatment on the patient's quality of life. The authors define anemia as a reduction in the oxygen-carrying capacity of blood. The typical anemia in kidney disease is a result of a decreased production of red blood cells by the bone marrow. This defect in red blood cell production is largely explained by the inability of the failing kidneys to secrete the hormone erythropoietin. The authors describe the symptoms of anemia, the role of hemodialysis in this anemia, and treatment options, notably treatment with recombinant erythropoietin. The book is created and published by the Kidney Transplant/Dialysis Association, a non-profit, all-volunteer organization of dialysis and transplant patients, their families, and friends. •

Carbohydrate Metabolism in Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 63-76. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on carbohydrate metabolism is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors note that many aspects of carbohydrate metabolism are impaired in patients with chronic renal failure (CRF). These derangements lead to glucose intolerance in these patients. The two major defects that underlie glucose intolerance in uremia are resistance to the peripheral action of insulin and impaired insulin secretion. When these two abnormalities are present in a particular patient, glucose intolerance ensues. Despite impaired insulin secretion, the increase in the blood levels of insulin in response to hyperglycemia may be decreased, normal, or increased. These variations are most likely due to differences in the degree of the impairment in insulin secretion or its metabolic clearance rate. The authors caution that these disturbances and the secondary hyperparathyroidism may all contribute to the increased risk for atherogenesis in patients with CRF. Postprandial (after meals) hyperglycemia in the glucose intolerant uremic patient may, by itself, be a risk factor for atherosclerotic cardiovascular disease. In addition, hyperinsulinemia and insulin resistant state may be associated with hypertension, which is an important risk factor for cardiac disease in uremia. 2 figures. 1 table. 88 references. (AA-M).

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Carnitine in Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 191-201. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on carnitine in renal failure is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. Carnitine is found in mammalian cells and has a number of well-established roles in intermediary metabolism. In humans, carnitine is derived from dietary sources and from endogenous biosynthesis. Foods with high carnitine content include meat and dairy products, which is consistent with the high carnitine concentrations in muscle and milk. The author discusses the potential changes associated with renal failure that may impact carnitine metabolism and function. Glucose and fatty acid metabolism are clearly altered in renal

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failure, and carnitine metabolism is closely integrated with overall fuel homeostasis. Dietary recommendations for renal failure patients may inadvertently limit dietary carnitine intake. As the kidney may be an important site of carnitine biosynthesis, production rates may be altered in renal disease. Normal carnitine elimination occurs via urinary excretion, and this will be altered in renal failure. There are ample reports showing the beneficial effects of carnitine treatment in patients with renal failure. The effects of carnitine therapy to improve skeletal muscle function and decrease intradialytic symptoms are of particular clinical importance. The author concludes that decisions about the use of carnitine supplementation in renal failure patients must be individualized and must be considered as a therapeutic trial; the need for continued treatment should be reassessed at regular intervals based on objective measurements of efficacy. 3 figures. 3 tables. 42 references. (AA-M). •

Drug Dosing and Toxicities in Renal Failure Source: in Mandal, A.K. and Nahman, N.S., Jr., eds. Kidney Disease in Primary Care. Baltimore, MD: Williams and Wilkins. 1998. p. 255-265. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. E-mail: [email protected]. PRICE: $39.95. ISBN: 0683300571. Summary: This chapter on drug dosing and toxicities in renal failure is from a textbook that provides primary care physicians with practical approaches to common clinical problems of kidney diseases. Changes in drug absorption, distribution, metabolism, and excretion must be considered in the therapeutic management of patients with impaired renal function or End Stage Renal Disease. The authors give general guidelines for the appropriate dosage adjustment of medications in patients with impaired renal function. Topics include the estimation of glomerular filtration rate (GFR), pharmacokinetics and pharmacodynamics (bioavailability, elimination coefficient and half-life, protein binding, volume of distribution), metabolism, and drug-induced nephrotoxicity (aminoglycosides, ACE inhibitors, amphotericin B, nonsteroidal anti-inflammatory agents, cisplatin, cyclosporine, radiographic contrast media, and nephrolithiasis or kidney stones). The authors note that gastrointestinal symptoms are common in renal patients and may prevent or delay oral absorption of drugs. Gastroparesis is especially common in renal patients with diabetes and may cause a delay in absorption of many drugs. 6 tables. 8 references.

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Drug-Nutrient Interactions in Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 799-815. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on drug-nutrient interactions is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The author notes that, in patients with chronic renal failure (CRF) or end-stage renal disease (ESRD), drug-nutrient interactions may lead to overt nutritional deficiencies, particularly when the general nutritional status is poor or specific subclinical nutritional deficiencies already exist. The author reviews those drug-nutrient interactions that may result from medicines or food supplements that are commonly or occasionally used in patients with CRF or ESRD. Patients with advanced CRF and those on maintenance

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dialysis are often prescribed food supplements such as vitamins, iron preparations, or phosphate binders. Topics include the effect of food intake on drug absorption; the effects of nutrients on drug metabolism; the interactions of food supplements with drugs; drug-induced nutritional deficiencies, including vitamin, mineral, and traceelement deficiencies; interactions of cyclosporine A with nutrients; and enteral tube feeding and oral drug administration. 6 tables. 101 references. (AA-M). •

Lipid Metabolism in Renal Disease and Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 35-62. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on lipid metabolism is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. In uremia, the distribution of lipid and apolipoproteins in the lipoprotein density classes is distorted. The disorder is complex and varies substantially within groups of patients treated with different renal replacement methods (e.g., hemodialysis, CAPD, transplantation). Abnormalities in lipid metabolism can be detected in the patient early as renal function begins to decline. The author summarizes the most characteristic patterns of serum lipids in patients with renal disease and renal failure. Guidelines for the detection, evaluation, and treatment of hypercholesterolemia in adults have been established in the U.S. and Europe. These guidelines recommend that total cholesterol levels be used for screening purposes. All persons in the so-called high category (cholesterol greater than 240 mg per dL) require measurements of low-density lipoprotein (LDL) cholesterol levels; the measurements are used as a guide to the selection of treatment. The chapter concludes with recommended treatment and patient care management strategies. 4 figures. 3 tables. 153 references. (AA-M).

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Protein and Amino Acid Metabolism in Renal Disease and Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 1-33. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on protein and amino acid metabolism is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors discuss alterations in protein and amino acid metabolism that are well recognized complications of acute and chronic renal failure and may contribute to wasting. As renal function declines, nitrogenous wastes accumulate, eventually resulting in symptomatic uremia. Changes in protein turnover and amino acid oxidation have also been described in the nephrotic syndrome when the glomerular filtration rate was normal, and in patients with early diabetic nephropathy. Finally, complications of renal failure (i.e., metabolic acidosis) may increase protein and amino acid catabolism and contribute to the loss of lean body mass. The authors note that recent advances in molecule and cellular biology have provided insight into the regulation of proteolysis and have indicated that accelerated protein catabolism in renal failure is due, at least in part, to activation of specific proteolytic pathways. Evidence that growth factors and inhibitors of proteolysis may block catabolism in experimental animals suggests a

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potential therapeutic role in patients with renal failure. 7 figures. 1 table. 141 references. (AA-M). •

Rehabilitative Exercise Training in Chronic Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 817-841. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on rehabilitative exercise training in chronic renal failure (CRF) is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. Exercise programs potentially have two distinct benefits for the patient with renal disease: psychologic and physiologic. The psychologic benefits of exercise are beginning to be understood; exercise programs generally have marked antidepressant effects. Exercise programs that focus on reaping these psychologic benefits can be quite successful in improving exercise tolerance and the overall quality of life. In contrast to programs designed to yield physiologic benefits, these programs can use exercise modalities and schedules at the convenience of the rehabilitation unit (i.e., more easily worked into the dialysis schedule). The author also summarizes exercise design features for physiologic gains for patients with CRF. Topics include structural and biochemical changes induced by training in healthy persons; characteristics of an effective exercise training program; the causes of exercise intolerance in patients with renal failure, including anemia, myopathy, cardiovascular dysfunction, carnitine deficiency, and deconditioning; guidelines for exercise training programs in patients with CRF; and exercise prescription recommendations for chronic dialysis patients. 1 figure. 2 tables. 134 references. (AA-M).

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Renal Failure Source: in Blandy, J. Lecture Notes on Urology. Malden, MA: Blackwell Science, Inc. 1998. p.112-120. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $39.95. ISBN: 0632042028. Summary: This chapter on renal (kidney) failure is from an undergraduate medical textbook in the field of urology and urological surgery. The author discusses acute renal failure (ARF), chronic renal failure (CRF), dialysis, and renal transplantation. The causes of ARF fall into three main categories which often occur together: poor renal perfusion, renal tubular poisoning, and renal tubular blockage. Sometimes renal function deteriorates very slowly, and the patient may be kept well on a diet low in protein. But eventually, dialysis is called for, often because of intolerable symptoms. Much of the information is presented in diagrams or illustration format for ease of use. 9 figures. 13 references.

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Renal Physiology and the Pathology of Renal Failure Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 25-34.

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Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: This chapter on renal physiology and the pathology of renal failure is from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. The author of the chapter reviews the two prime functions of the normal kidney: elimination of metabolic wastes and other toxic materials; and maintenance of a stable composition of the body's internal fluid environment. In addition, kidneys also have several endocrine functions including: production of renin, which affects sodium, fluid volume, and blood pressure; erythropoietin formation, which controls red cell production in the bone marrow; production of prostaglandins; and involvement in the kallikreinkinin system. Also, the normal kidney is a receptor site for several hormones: antidiuretic hormone (ADH), produced by the pituitary, which reduces the excretion of water; aldosterone, produced by the adrenal cortex, which promotes sodium retention and enhances secretion of potassium and hydrogen ion; and parathyroid hormone, which increases phosphorus and bicarbonate excretion and stimulates conversion of vitamin D to the active form. The author describes each of these functions in detail, and the related problems that occur during reduced kidney function or kidney failure. 3 figures. 1 table. •

Causes, Manifestations, and Assessment of Malnutrition in Chronic Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 245-256. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on the causes, manifestations, and assessment of malnutrition in chronic renal failure (CRF) is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The author notes that patients with chronic renal insufficiency and those with end-stage renal disease (ESRD) often manifest signs of wasting and malnutrition. The initiation of dialysis therapy in the malnourished patient often fails to improve nutritional status. The author describes the causes of malnutrition in patients with renal failure and those treated with maintenance dialysis. Renal disease is associated with anorexia and alterations in taste; these symptoms may lead to decreased dietary intake and subsequent malnutrition. CAPD is also associated with abnormal patterns of dietary intake, due to the large amount of fluid in the peritoneal cavity and the effect of glucose absorption on appetite. Patients undergoing maintenance hemodialysis have reduced gastric emptying, and the frequent coexistence of diabetes mellitus may also be associated with gastroparesis, further suppressing intake. Frequent intercurrent illness may increase catabolism and further impair nutritional status. Inadequate dialysis is another possible cause of malnutrition in maintenance dialysis patients. The author also outlines the methods available to assess nutritional status in these patients. 1 figure. 2 tables. 52 references. (AA-M).

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Epidemiology of Chronic Renal Failure and Guidelines for Initiation of Hemodialysis Source: in Wilson, S.E. Vascular Access: Principles and Practice. 4th ed. St. Louis, MO: Mosby, Inc. 2002. p. 76-81. Contact: Available from Elsevier, Health Sciences Division, 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Website: www.us.elsevierhealth.com. PRICE: $99.00. ISBN: 0323011888. Summary: This chapter on the epidemiology of chronic renal (kidney) failure (CRF) and guidelines for initiation of hemodialysis (HD) is from a text that reviews the principles and practice of vascular access, including that used for hemodialysis and for critical care, chemotherapy, and nutrition. Decisions concerning the timing of the initiation of dialysis are based on careful monitoring and evaluation of various clinical and biochemical features of renal failure. In this chapter, the authors provide a brief overview of the main clinical and biochemical manifestations of CRF. Topics include biochemical abnormalities, cardiovascular features, neurologic features, hematologic (blood) abnormalities, gastrointestinal abnormalities, immunologic abnormalities, endocrine abnormalities, and dermatologic (skin) abnormalities. The chapter concludes with brief sections offering guidelines for initiation of HD in CRF patients, and recommendations for vascular access. 1 table. 35 references.

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Nutritional Management of Nondialyzed Patients with Chronic Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 479-531. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on the nutritional management of nondialyzed patients with chronic renal failure (CRF) is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The author stresses that the patient with CRF has alterations in both the dietary requirements and tolerance for most nutrients. Causes of these disorders include decreased (or occasionally increased) urinary, intestinal, and dermal excretion and intestinal absorption. Causes may also include altered metabolism of individual nutrients or their metabolites or products. The author also notes that the nutritional status of the patient undergoing maintenance hemodialysis or peritoneal dialysis is a strong predictor of morbidity and mortality. Other topics include training and monitoring the patient undergoing dietary therapy; dietary therapy for patients who are not yet receiving dialysis therapy, including recommended nutrient intakes; management of the patient with diabetic nephropathy; nutritional management during catabolic stress; and the use of growth factors. Detailed guidelines are provided for patient care management. 4 figures. 3 tables. 270 references. (AA-M).

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Progression of Chronic Renal Failure Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 843-856. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail:

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[email protected] Website: www.elsevierhealth.com. PRICE: $199.00. ISBN: 723432589. Summary: This chapter on the progression of chronic renal (kidney) failure (CRF) is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The authors of this chapter discuss definition and incidence, the epidemiology (incidence and prevalence) of CRF, natural history, factors affecting the progression of CRF, the mechanisms of progression of CRF, and clinical interventions in patients with CRF, including dietary interventions, and drug therapy. The authors conclude with a list of general recommendations for the management of patients with progressive CRF. The chapter is clinically focused and extensively illustrated in full color. 8 figures. 6 tables. 57 references. •

Trace Element Metabolism in Renal Disease and Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 395-414. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on trace element metabolism is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. It is generally accepted that the term 'trace element' applies to elements that occur in the body at concentrations of less than 50 mg per kg under normal conditions. The definition of 'essential' trace elements is that the element should be present in healthy tissues; deficiency of the element consistently produces functional impairment; the abnormalities induced by the deficiency are always followed by specific biochemical changes; and addition of the element prevents or corrects these changes. Topics include methodology for the measurement of trace elements; trace element concentrations in uremia; the potential contribution of trace elements to the uremic syndrome, including impairment of renal function, susceptibility to cancer, cardiovascular disease, glucose intolerance, bone disease, anemia, enzyme dysfunction, encephalopathy and coma, and immune deficiency; factors affecting trace element concentration, including inadequate intake, decreased availability, impaired reabsorption, excessive excretion, and extracorporeal losses; specific examples relating to aluminum, lead, selenium and arsenic, zinc, vanadium, silicon, and chromium; and therapeutic considerations. The authors caution that the treatment of uremia by dialysis strategies may cause changes in trace element handling. Trace elements should be considered in the case of any unexplained toxic event in uremia. 5 tables. 89 references. (AA-M).

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Vitamin Metabolism and Requirements in Renal Disease and Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 415-477. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on vitamin metabolism and requirements is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors discuss several factors that may enhance the risk of abnormal vitamin levels in renal disease: decreased vitamin intake caused by anorexia, unpalatability of

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prescribed diets, or a dietary prescription that contains insufficient vitamins; increased degradation or endogenous clearance of vitamins from blood; elevated levels of vitamin binding proteins; losses of vitamins into dialysate; excretion of protein-bound vitamins by nephrotic patients; and interference of medicines with the absorption, excretion, and metabolism of vitamins. The authors review each of the common vitamins for its normal biochemistry and metabolism, the effect of renal disease and renal failure on these processes, and the clinical spectrum of vitamin disorders in these conditions. The authors propose guidelines concerning the needs for supplementation. Vitamins discussed are A, E, K, B1, B2, B6, B12, C, folates, niacin, biotin, and pantothenic acid. The authors conclude by calling for additional research to address vitamin supplementation in renal failure patients, particularly those on dialysis. 2 figures. 7 tables. 249 references. (AA-M). •

Haemodialysis in Type 1 and Type 2 Diabetic Patients with End Stage Renal Failure Source: in Mogensen, C.E. Kidney and Hypertension in Diabetes Mellitus. 3rd ed. Norwell, MA: Kluwer Academic Publishers. 1997. p. 481-488. Contact: Available from Kluwer Academic Publishers. 101 Philip Drive, Assinippi Park, Norwell, MA 02061. (617) 871-6600. Fax (617) 871-6528. PRICE: $130.00. ISBN: 0792343530. Summary: This chapter, from a book on the kidney and hypertension in diabetes mellitus, addresses the use of hemodialysis in patients with end-stage renal disease (ESRD) and type 1 or type 2 diabetes. The authors consider epidemiology, survival and causes of death, predictors of survival, metabolic control while on renal replacement therapy (dialysis), managing diabetic complications while on renal replacement therapy, and kidney transplantation in the patient with diabetes. The authors note that the number of patients with diabetes entering renal replacement programs has increased in all Western countries. Hemodialysis is the preferred modality of treatment, hemofiltration and CAPD being used only in a minority of cases. The proportion of patients undergoing renal or combined renal and pancreatic transplantation is rising. Survival in patients with diabetes compared to nondiabetic patients is worse for all renal replacement modalities. This is mainly due to cardiovascular death. Cardiac death is poorly predicted by the level of blood pressure and blood pressure related target organ damage, while cholesterol and other lipid parameters are potent predictors. Common clinical problems in the dialysis patient with diabetes include metabolic control, visual disturbance, sequelae of autonomic polyneuropathy, amputation, and vascular access. 1 figure. 2 tables. 36 references. (AA-M).

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Principles of Drug Therapy in Renal Failure Source: in Greenberg, A., et al., eds. Primer on Kidney Diseases. New York, NY: National Kidney Foundation. 1994. p. 318-323. Contact: Available from Academic Press. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 321-5068. PRICE: Paperback $49.95 (paper). ISBN: 0122992318. OR $99 (hardback). ISBN: 012299230X. Summary: This chapter, from a comprehensive textbook of clinical nephrology, provides an overview of the principles of drug therapy in renal failure. The author emphasizes the complex problems of drug therapy, including drug interactions, reduced drug clearance, and altered drug effects, in patients with renal insufficiency. Topics covered include pharmocokinetic considerations, including bioavailability and absorption, protein binding, volume of distribution, metabolism, and renal excretion; the effect of

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renal failure on pharmacodynamics; adjusting dosages for renal failure; estimation of glomerular filtration rate (GRF); loading doses; maintenance doses; drug removal by dialysis or hemofiltration; and drug complications in patients with renal failure, including cardiovascular preparations, antimicrobials, central nervous system agents including analgesics, immunosuppressive agents, gastrointestinal drugs, endocrine preparations, and the nephrotic syndrome and diuretic resistance. 1 figure. 2 tables. 10 references. •

Nutrition Assessment in Chronic Renal Failure Source: in American Dietetic Association. Clinical Guide to Nutrition Care in End-Stage Renal Disease. Chicago, IL: American Dietetic Association. 1994. p. 5-15. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard Chicago, IL 60606-6995. (312) 899-0040. PRICE: $24 for members; $28 for non-members; plus shipping and handling. ISBN: 0880911247. Summary: This chapter, from a manual that provides guidelines for the clinical nutrition care of patients with end-stage renal disease (ESRD), discusses nutrition assessment in chronic renal failure. Topics covered include the anthropometric evaluation, notably actual body weight, height, estimation of frame size, desirable body weight, estimation of body fat and protein reserves, and anthropometric measurements for children; clinical signs of nutrient deficiency; the patient's diet history; evaluation of biochemical parameters, including serum proteins, blood urea nitrogen, creatinine, potassium, sodium, calcium, phosphorus, calcium-phosphorus product, alkaline phosphatase, magnesium, glucose, iron studies, and lipids; urea kinetic modeling; and the use of the prognostic nutrition index (PNI). Information is presented in a concise style, often in list format, for ease of use. 58 references.

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Renal Failure and Secondary Hyperparathyroidism Source: in Pellitteri, P.; McCaffrey, T.V. Endocrine Surgery of the Head and Neck. Florence, KY: Thomson Learning. 2003. p. 389-400. Contact: Available from Thomson Learning, Attn: Order Fulfillment. P.O. Box 6904 Florence, KY 41022 (800) 347-7707. Fax (800) 487-8488. E-mail: [email protected]. Website: www.delmar.com. PRICE: $179.95 plus shipping and handling. ISBN: 076930091x. Summary: This chapter, from a textbook on endocrine surgery of the head and neck, covers renal (kidney) failure and secondary hyperparathyroidism (HPTH). The authors note that secondary HPTH is a complex process. Hyperplasia (overgrowth) of the parathyroid glands and increase in the serum PTH (parathyroid hormone) levels appear early in the development of renal disease. Medical treatment of HPTH is aimed at reducing serum phosphatase levels, increasing serum calcium levels, administering vitamin D analogs, and maintaining an appropriate metabolic equilibrium with adequate dialysis. The most common indications for surgical treatment of secondary HPTH are the development of renal osteodystrophy (bone disease), severe pruritus (itching) associated with HPTH, calciphylaxis, and tumoral calcinosis. Less clear indications for surgery are easy fatigability, proximal muscle weakness and anemia. Patients with secondary HPTH treated surgically can expect substantial improvements in bone and joint pain and pruritus in most cases. Amelioration of fatigue and generalized well being are often observed, albeit harder to quantify. Surgical techniques most commonly employed include subtotal parathyroidectomy and total parathyroidectomy with autotransplantation. There may be a role for minimally

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invasive approaches, such as endoscopic parathyroidectomy and percutaneous ethanol ablation, which are currently still investigational. 3 figures. 95 references. •

Cholesterol Emboli: A Common Cause of Renal Failure Source: in Coggins, C.H., Hancock, E.W., and Levitt, L.J., eds. Annual Review of Medicine. Palo Alto, CA: Annual Reviews Inc. 1997. Volume 48: 375-385. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. E-mail: [email protected]. PRICE: $60.00 for individuals; $120.00 for institutions. ISBN: 0824303555. ISSN: 00664219. Individual chapter reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. Base price $13.50 per article. Summary: This chapter, from the Annual Review of Medicine, describes cholesterol emboli, a common cause of renal failure. Cholesterol embolization (CE), usually occurring in males in their sixth or seventh decade of life, can affect multiple organ systems, including the kidney. The author notes that interventive diagnostic procedures and aortic surgery greatly increase the risk of CE. Rapid or insidious progression of renal failure in association with surgical or diagnostic radiologic procedures should suggest this diagnosis. Progressive renal insufficiency in older patients with generalized arterial disease should suggest ischemic nephropathy secondary to bilateral renal artery stenosis, renal CE, or both. Recent worsening of hypertension is characteristic of either diagnosis. A number of clinical conditions can simulate renal CE, and final differentiation may be possible only by renal biopsy. The author stresses that aggressive, supportive management of renal CE is warranted because renal function may stabilize and, in a limited number of cases, may even improve. 2 figures. 2 tables. 44 references. (AA).

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Bone Disease in Moderate Renal Failure: Cause, Nature, and Prevention Source: in Coggins, C.H., Hancock, E.W., and Levitt, L.J., eds. Annual Review of Medicine. Palo Alto, CA: Annual Reviews Inc. 1997. Volume 48: 167-176. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. E-mail: [email protected]. PRICE: $60.00 for individuals; $120.00 for institutions. ISBN: 0824303555. ISSN: 00664219. Individual chapter reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. Base price $13.50 per article. Summary: This entry describes the cause, nature, and prevention of bone disease in moderate renal failure. Patients with end-stage renal disease (ESRD) present with two primary types of bone disorders: a high-turnover osteodystrophy characterized by osteitis fibrosa, and a low-turnover osteodystrophy characterized initially by osteomalacia and, more recently, by adynamic or aplastic bone disease. The author reviews the clinical presentation, pathogenesis, and laboratory findings of patients with these two disorders. The author discusses the important roles of phosphorus binding, vitamin D administration, and correction of acidosis in the prevention and treatment of bone disease in these patients. As renal function declines, dietary phosphorus intake should be restricted to prevent its accumulation. The author cautions that, although dialysis removes phosphate from the body, it is a rare dialysis patient who will not require phosphate binders in addition to dietary phosphorus restriction to control serum phosphate. Vitamin D sterols are effective in decreasing parathyroid hormone (PTH) secretion and bone turnover and in increasing serum calcium. Calcium carbonate is useful as a buffer against acidosis; it has been shown to increase the extracellular fluid

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bicarbonate concentration. Alkalosis should be avoided, as it promotes calcium phosphate deposit in soft tissues. 2 figures. 46 references. (AA-M). •

Nutrition Care of the Hospitalized Patient With Renal Failure Source: in American Dietetic Association. Clinical Guide to Nutrition Care in End-Stage Renal Disease. Chicago, IL: American Dietetic Association. 1994. p. 187-189. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard Chicago, IL 60606-6995. (312) 899-0040. PRICE: $24 for members; $28 for non-members; plus shipping and handling. ISBN: 0880911247. Summary: This item, from a manual that provides guidelines for the clinical nutrition care of patients with end-stage renal disease (ESRD), is an appendix that summarizes the nutrition care of the hospitalized patient with renal failure. The author notes that the presentation of multiple needs in this patient population requires treatment of the whole patient in whom kidney failure is a component and not the sole or main focus. Specific topics discussed include malnutrition in renal failure; the effect on patient outcome; screening for nutrition problems; conditions placing the patient at further risk; and formulation of the nutrition care plan. 4 references.

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Nutrition Support in Renal Failure Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 327-342. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 877-1600 or (312) 899-0040. Fax (312) 899-4899. PRICE: $59.95 for members, $70.00 for nonmembers. ISBN: 0880911530. Summary: This section outlining guidelines for nutritional support in renal failure is from a manual that serves as a nutrition care guide for dietetics professionals, physicians, nurses, and other health professionals. The manual integrates current knowledge of nutrition, medical science, and food to set forth recommendations for healthy individuals and those for whom medical nutrition therapy (MNT) is indicated. The goal of nutrition support in renal failure is to achieve or maintain optimal nutritional status and preserve remaining kidney function through alterations in fluid, protein, and electrolyte intake. Nutrition support is used for patients with acute or chronic renal failure who are unable to meet nutrient requirements by oral intake. Impaired kidney function results in altered filtration, reabsorption, and excretion of metabolites and diminished urinary output. Hormonal function is also affected and may cause impaired vitamin D activation, impaired red blood cell synthesis, and glucose intolerance. The alterations differ with the cause of renal impairment; therefore, sodium, potassium, blood urea nitrogen (BUN), phosphate, urinary output, and the presence of acidosis must be monitored. The text notes the purpose, use, modifications, and adequacy of the diet. A separate section discusses enteral and parenteral nutrition, continuous arteriovenous hemofiltration, and the use of modified formulas (essential amino acids). 3 tables. 57 references. (AA-M).

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Nutrition Management of Chronic Renal Failure Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 535-553.

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Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 877-1600 or (312) 899-0040. Fax (312) 899-4899. PRICE: $59.95 for members, $70.00 for nonmembers. ISBN: 0880911530. Summary: This section providing guidelines for the nutritional management of chronic renal failure (CRF) is from a manual that serves as a nutrition care guide for dietetics professionals, physicians, nurses, and other health professionals. The manual integrates current knowledge of nutrition, medical science, and food to set forth recommendations for healthy individuals and those for whom medical nutrition therapy (MNT) is indicated. The diet for CRF is designed to meet nutritional requirements, prevent malnutrition, and maintain acceptable blood chemistries, blood pressure, and fluid status in patients with impaired renal (kidney) function. The text notes the purpose, use, modifications, and adequacy of the diet. The diet is used for patients with CRF requiring hemodialysis or peritoneal dialysis treatments. Generally, the diet controls intake of protein, potassium, sodium, phosphorus, and fluids. Additional modifications of fat, cholesterol, triglycerides, and fiber may be necessary based on individual requirements. The section also outlines the related physiology. Charts provide a brief sample menu, food lists, and calculation figures for planning the CRF diet. 5 tables. 25 references. (AAM).

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CHAPTER 7. MULTIMEDIA ON RENAL FAILURE Overview In this chapter, we show you how to keep current on multimedia sources of information on renal failure. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on renal failure is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “renal failure” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “renal failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on renal failure: •

End-Stage Renal Disease: Preventing Dialysis Through Early Recognition and Intervention Source: Secaucus, NJ: Network for Continuing Medical Education (NCME). 1992. Contact: Available from NCME. One Harmon Plaza, Secaucus, NJ 07094. (800) 223-0272 or, in New Jersey, (800) 624-2102, or (201) 867-3550. PRICE: $50 for 2-week rental or $75 for purchase. Available only to NCME subscribers; subscriber fees as of 1995 are $1,920 for VHS subscription, $2,120 for U-matic subscription. Summary: Although deaths in the United States from stroke and coronary artery disease are declining, the incidence of renal failure, another major consequence of hypertension, continues to grow. In this continuing education videotape program, viewers are taught early recognition of end-stage renal disease (ESRD) and appropriate intervention, in an attempt to eliminate or reduce the need for dialysis in hypertensive and diabetic patients. The program focuses on the identification of the very early signs of kidney impairment and the appropriate modes of therapy. (AA-M).

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Diabetes: From Detection to Treatment Source: Calhoun, KY: NIMCO. 1994. (videocassette). Contact: Available from NIMCO. P.O. Box 9, 117 Highway 815, Calhoun, KY 423270009. (800) 962-6662 or (502) 273-5050. Fax (502) 273-5844. PRICE: $89.95. Order number: NIM-SM-CD1-V. Summary: This video takes the viewer through the medical detection of diabetes. The model it presents of the cause of diabetes hypothesizes that an environmental trigger in a genetically susceptible person causes inflammation that eventually destroys the cells of the pancreas and leads to a reduction in insulin. The video highlights diabetes symptoms, including polyuria, polydipsia, polyphagia, weight loss, and blurred vision. It explains why people with diabetes consume so much fluid and why they have increased urination. Among the other topics covered are diabetes education, medications and their side effects, diabetic retinopathy, cardiovascular disease, atherosclerosis, foot problems and neuropathy, and renal failure. The video includes numerous comments from physicians and patients.

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Renal Disorders: Fluids and Electrolytes Source: in Schwartz, R.S., ed. Aging and the Elderly: A Review Course of Geriatric Medicine. Seattle, WA: University of Washington School of Medicine. 1992. Tape 8, Section 29). Contact: Available from CME Conference Video, Inc. 2000 Crawford Place, Suite 100, Mount Laurel, NJ 08054. (800) 284-8433. PRICE: $549; plus $18.25 shipping and handling; Group Practice Package $150 plus $5.25 shipping and handling. Program Number 053. Summary: This videotape presentation is part of the 16th Annual Symposium on Aging and the Elderly, a continuing medical education (CME) program offered through the University of Washington School of Medicine. This program covers renal disease, notably fluid and electolytes physiology, in the elderly. Topics include anatomic changes with aging; changes in renal blood flow and glomerular filtration rate that accompany aging; changes in water homeostasis; and the diagnosis and treatment of hyponatremia, hypernatremia, sodium homeostasis, hyperkalemia, renal tubular acidosis, renal failure in the elderly, and end-stage renal disease. The proceedings include an outline of the author's comments on these topics. The videotape program includes the question-and-answer period conducted after the section.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “renal failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on renal failure: •

Diet and the Retardation of the Progression of Chronic Renal Failure Source: Bethlehem, PA: St. Luke's Hospital. 1991.

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Contact: Available from St. Luke's Hospital. Nutrition Services-Renal, 801 Ostrum Street, Bethlehem, PA 18015. (215) 954-4000. ATTN: Emilia Johns. PRICE: Contact directly for details. Summary: This audiocassette presents a program from a one-day symposium, held in October 1991, that focuses on the nutritional assessment and nutritional intervention in the treatment of patients with chronic renal failure (CRF). The speaker, Joel D. Kopple, a professor of medicine and public health, discusses diet and the retardation of the progression of CRF. Special attention is directed at the nutritional aspects of the treatment of the patient in the earlier stages of CRF. The symposium was designed for dietitians and for students studying to become dietitians.

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CHAPTER 8. PERIODICALS AND NEWS ON RENAL FAILURE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover renal failure.

News Services and Press Releases One of the simplest ways of tracking press releases on renal failure is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “renal failure” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to renal failure. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “renal failure” (or synonyms). The following was recently listed in this archive for renal failure: •

Renal failure after non-kidney transplantation greatly raises risk of death Source: Reuters Medical News Date: September 03, 2003

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High phenylacetic acid in chronic renal failure may lead to vascular disease Source: Reuters Medical News Date: July 18, 2003

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Women at increased risk of acute renal failure after open-heart surgery Source: Reuters Medical News Date: April 10, 2003

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N-acetylcysteine prevents renal failure in animal model Source: Reuters Medical News Date: April 03, 2003

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Dual kidney-pancreas transplant can improve survival in diabetic renal failure Source: Reuters Medical News Date: March 13, 2003

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Renal failure does not preclude mechanical support as bridge to cardiac transplant Source: Reuters Industry Breifing Date: February 20, 2003

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Low ferritin level not predictive of renal failure after cardiac surgery Source: Reuters Medical News Date: February 18, 2003

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Pentoxifylline reduces protein catabolism in chronic renal failure Source: Reuters Industry Breifing Date: December 24, 2002

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Diuretics may be deleterious in oliguric acute renal failure, by delaying dialysis Source: Reuters Industry Breifing Date: November 26, 2002

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Hemofiltration recommended for infection-associated renal failure in developing countries Source: Reuters Medical News Date: September 19, 2002

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HBV vaccine most effective pretransplant in children with chronic renal failure Source: Reuters Industry Breifing Date: September 10, 2002

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Kidney failure strikes 1 in 13 African Americans Source: Reuters Health eLine Date: June 04, 2002

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Antioxidant vitamins may play a role in chronic renal failure Source: Reuters Medical News Date: April 08, 2002

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Daily hemodialysis reduces mortality in acute renal failure patients Source: Reuters Medical News Date: January 30, 2002

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Daily dialysis for kidney failure lengthens life Source: Reuters Health eLine Date: January 30, 2002

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Vitamin E hemodialyzer improves neutrophil function in renal failure patients Source: Reuters Industry Breifing Date: January 24, 2002

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Nonnarcotic analgesic use tied to development of chronic renal failure Source: Reuters Industry Breifing Date: December 21, 2001

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Painkillers linked to kidney failure Source: Reuters Health eLine Date: December 19, 2001

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Even low-level cadmium exposure increases the risk of renal failure Source: Reuters Medical News Date: December 10, 2001

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Heart surgery tied to kidney failure risk in women Source: Reuters Health eLine Date: October 15, 2001

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Off-pump bypass appropriate for patients with highest stroke, renal failure risk Source: Reuters Industry Breifing Date: October 02, 2001

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High levels of a hematopoiesis inhibitor in renal failure raise erythropoietin needs Source: Reuters Medical News Date: September 20, 2001

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Cephalosporin-induced nonconvulsive status epilepticus seen in renal failure patients Source: Reuters Medical News Date: September 05, 2001

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Use of dopamine in acute renal failure unjustified Source: Reuters Industry Breifing Date: August 28, 2001

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Moderate analgesic use not associated with renal failure in healthy men Source: Reuters Industry Breifing Date: July 17, 2001

•

Drug dosing in renal failure patients optimized by pharmacist input on rounds Source: Reuters Medical News Date: July 13, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “renal failure” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “renal failure” (or synonyms). If you know the name of a company that is relevant to renal failure, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “renal failure” (or synonyms).

Newsletters on Renal Failure Find newsletters on renal failure using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “renal failure.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “renal failure” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Kidney Failure in Sarcoidosis Source: Sarcoidosis Networking. 8(3): 3. 2000. Contact: Available from Sarcoid Network Association. Sarcoidosis Networking, 13925 80th Street East, Puyallup, WA 98372-3614. Email: [email protected]. Summary: Sarcoidosis is a chronic, progressive systemic granulomatous (causing lesions) disease of unknown cause (etiology), involving almost any organ or tissue, including the skin, lungs, lymph nodes, liver, spleen, eyes, and small bones of the hands or feet. This brief article, from a newsletter for patients with sarcoidosis, reviews the complications of kidney failure in sarcoidosis. Granulomatous infiltration of the kidney may be present in as many as 40 percent of patients with sarcoidosis, but it is rarely

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extensive enough to cause renal (kidney) dysfunction. The lesions are usually responsive to steroid therapy. Kidney failure has also been diagnosed in patients with sarcoidosis without the presence of lesions, possibly due to hypercalcemia (too much calcium in the blood), involvement of the glomerular filter system, and renal arteritis (inflammation of the arteries of the kidney), which may be associated with severe high blood pressure. It is recommended that all people with active sarcoidosis be screened for hypercalciuria (high levels of calcium in the urine). This may precede development of hypercalcemia, which should be treated. Glucocorticoids are the main choice of therapy and do seem to reduce levels of urinary calcium to normal within a few days. People with sarcoidosis may also have severe pain; the frequent use of pain medication can be another cause of kidney failure. People who take pain medication should ask their physicians to evaluate their kidneys on a regular basis. 9 references.

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “renal failure” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on renal failure: •

Growth Retardation Affects Kidney and Liver Transplant Recipients Source: Transplant Chronicles. 4(4): 16, 19. 1997. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Summary: Growth retardation, or short stature, is a serious problem in children with chronic renal failure (CRF) and liver failure, and creates a challenge in posttransplant rehabilitation. This newsletter article describes this growth retardation and its causes. The author notes that children with CRF may suffer from short stature prior to transplantation, especially if CRF begins during infancy. Resistance to growth hormone, a substance that is responsible for normal growth of bone and cartilage, may cause short stature. Malnutrition also accounts for poor growth in these children and can be caused by inadequate caloric and protein intake, poor appetite, higher than normal caloric requirements, and protein losses on dialysis. Kidney transplantation results in an increased rate of growth; however, it usually does not occur fast enough for children to attain normal adult height. Prednisone is known to have an adverse effect on linear growth, but how it does this is not fully understood. Although some children show significant improvement in growth when prednisone is discontinued, a number of children develop severe kidney rejection, requiring continuing high dose prednisone therapy. Poor function of the transplanted kidney may also have a negative impact on growth. This problem may be due to recurrent acute rejection, chronic rejection, or recurrence of the kidney disease that was present in the child's native kidneys. Due to the discouraging growth rate in the majority of children following kidney transplantation, a number of transplant centers have started using daily injections of recombinant human growth hormone in selected children and are reporting improved growth rates.

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•

Nephropathy in NIDDM as Compared With IDDM Source: Diabetes News. 16(2): 5-8. 1995. Contact: Available from Excerpta Medica. P.O. Box 1126, 1000 BC Amsterdam, Netherlands. Summary: In this article, the author reports on nephropathy in people with noninsulindependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). The author notes that renal disease in both NIDDM and IDDM is frequently associated with poor metabolic control as well as with elevated blood pressure. To date, these two risk factors appear to be the only ones that are clearly linked to the development of renal disease, though several other modifying factors are known. Topics covered include population-based studies of individuals without known diabetes; renal function at the clinical diagnosis of diabetes; normal albumin excretion and the transition to microalbuminuria; overt diabetic retinopathy; end-stage renal failure; epidemiological studies; and screening. 2 figures. 2 tables. 12 references. (AA-M).

•

Vascular Access Procedures for American Indian Dialysis Patients Source: IHS Primary Care Provider. 25(10): 153-158. October 2000. Contact: Available from Indian Health Service Clinical Support Center. Two Renaissance Square, Suite 780, 40 North Central Avenue, Phoenix, AZ 85004. (602) 3647777. Fax (602) 364-7788. E-mail: [email protected]. Website: www.ihs.gov. Summary: More than 300,000 patients are currently receiving treatment for chronic renal failure with chronic dialysis in the United States. Access complications are the leading cause for hospitalizations in this population. This article examines renal (kidney) failure and the complications of dialysis access in two groups of patients from two southwestern Native American tribes. As in the general population, comorbid conditions (illnesses in addition to the kidney disease) were common. In the group from Tribe A, 84 percent had diabetes and 97 percent had hypertension (high blood pressure). In the Tribe B group, 66 percent had diabetes and 80 percent had hypertension. Renal failure associated with diabetes mellitus and hypertension is largely preventable by maintaining strict control of serum glucose and blood pressure. There are three general treatment options for end stage renal disease (ESRD): no therapy (which results in death), peritoneal dialysis, and hemodialysis. In this article, the authors review results from 60 patients from Tribe A who had 81 primary dialysis access procedures over a 6 year period, and from 58 patients from Tribe B who had 94 primary dialysis access procedures over a three year period. The authors discuss the types of grafts and fistulas used, and the complications that can be encountered, including thrombosis (clotting), infection, and arterial insufficiency. In the groups covered in this paper, arteriovenous fistulas had a higher initial failure rate than PTFE (polytetrafluoroethylene) grafts in both patient populations, but those that last a year have longer patency than grafts. The primary and secondary patency rates for Tribe B are less than those for Tribe A patients for PTFE grafts. Radiologic thrombectomy with angioplasty has as good results as surgical revisions as a treatment for graft thrombosis. The authors conclude that early placement of access in patients with progressive ESRD reduces the need for temporary access procedures and may reduce the incidence of subclavian vein stenosis. 5 figures. 3 tables. 28 references.

•

Genes Behaving Badly Source: PKR Progress. 13(2): 4-5, 17. Spring 1998.

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Contact: Available from PKD (Polycystic Kidney Disease) Foundation. 9221 Ward Parkway, Suite 400 Kansas City, MO 64114.(800) PKD-CURE. Fax (816) 931-8655. Email:[email protected]. Website: www.pkdcure.org. Summary: One of the striking features of polycystic kidney disease (PKD) is the variability with which it affects people. Some individuals develop a modest number of cysts throughout their lifetime and do not even know they are affected by the disorder. Others develop a massive amount of cysts on their kidneys and reach renal failure at a young age. This article summarizes recent data from studies that are attempting to identify the factors and determine the processes that account for these differences. The author discusses three areas of study: interfamilial variability, intrafamilial variability, and intraindividual variability. The author describes how differences in the type of PKD or the influence of genetic modifiers may explain different disease presentations in different families; however, these differences do not cover variability between individuals. Careful analysis of early cystic kidneys reveals that only a small subset of tubules develop cysts. Researchers are trying to determine how the cells that go on to become cysts differ from those that do not. The author describes the focal nature of renal cyst formation and the molecular basis of focal cyst formation. A sidebar urges readers who are interested in participating in research studies to contact the study coordinator (telephone number provided). 2 figures. •

Anemia-Related Fatigue: Feeling Tired Isn't Always Normal Source: PKR Progress. 15(3): 10. Fall-Winter 2000. Contact: Available from PKD (Polycystic Kidney Disease) Foundation. 9221 Ward Parkway, Suite 400 Kansas City, MO 64114.(800) PKD-CURE. Fax (816) 931-8655. Email:[email protected]. Website: www.pkdcure.org. Summary: This article from a newsletter for patients with polycystic kidney disease (PKD) explores the problem of anemia related fatigue in patients with kidney diseases. The author notes that since basic treatments are available for PKD, health care providers and researchers are now turning their attention to quality of life medical issues such as anemia. Anemia develops in virtually all patients with renal failure during the course of their disease. Health care providers now know that by intervening earlier in the disease process (in patients with chronic kidney disease who are not yet on dialysis), patients can realize a number of benefits and enhance their overall well being. The kidneys produce about 90 percent of the body's supply of the hormone erythropoietin (EPO); EPO is a major catalyst in the production of red blood cells in the bone marrow, so a reduction in EPO due to kidney disease usually results in fewer red blood cells and insufficient oxygen reaching the body tissues. The author explains the two primary diagnostic tests used to check for anemia, hematocrit (HCT) and hemoglobin. Anemia related fatigue is often described as a total lack of energy or debilitating exhaustion that can last days, weeks, or months. Fatigue can also have mental and emotional effects. The author cautions that because of its gradual onset and insidious nature, fatigue is often overlooked, underrecognized, and undertreated. Readers are encouraged to work with their physicians to address any problems or symptoms of fatigue.

•

Interpreting Laboratory Values in the Renal Patient Source: Renal Nutrition Forum. 19(1): 1, 3-5. Winter 2000. Summary: This article, from a newsletter for renal (kidney) dietitians, focuses on interpreting laboratory values in the renal patient. The author reminds readers that every measurement in the clinical laboratory is made with an accuracy and precision

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determined in large part by the test methodology. The author explains the differences between accuracy (how well does the test measure what it is supposed to measure, i.e., validity) and precision (reproducibility, i.e., reliability). Renal failure itself also has a variety of effects on laboratory values. The most common of these result from loss of renal clearance. The renal handling of certain biochemical markers (e.g., serum protein prealbumin) must be considered in clinical interpretation of their values. Another effect from renal failure on laboratory values is the accumulation of normally cleared substances that interfere with an assay; common examples include therapeutic drug monitoring (for phenytoin and vancomycin, for example). Inability to take this reduction in clearance into consideration may lead to under dosing of the drugs involved. A further complication arises when drugs are bound to protein, especially albumin, in plasma (blood). The author concludes that both the clinician and the laboratory need to be aware of the importance of method selection when dealing with patients with renal failure. Two way communication is the key to the proper use of the laboratory results. One appendix reprints a sample monthly lab report, listing the lab test and acceptable level, a blank space for the patient's value to be entered, what to do if the level is too high or too low, the symptoms that the patient may experience, and why the level may have gotten high or low. The lab tests included are: BUN (blood urea nitrogen), albumin, potassium, phosphorus, calcium, and average fluid gain. 1 figure. 3 tables. 9 references. •

Nutrition: Preserving Muscle and Providing Energy for Rehabilitation Source: Renal Rehabilitation Report. 6(3): 7. May-June 1998. Contact: Available from Life Options Rehabilitation Program. Medical Education Institute, Inc, 414 D'Onofrid Drive., Suite 200, Madison, WI 53719. (608) 833-8033. Email: [email protected]. Summary: This brief article reviews the role of nutrition in patients with end-stage renal disease (ESRD), particularly the importance of adequate nutrition as a prerequisite for rehabilitation. Dialysis patients have an increased need for protein, however, due to such factors as anorexia, nausea, comorbid conditions, or restrictive and unpalatable diets, they often have difficulty taking in enough protein to meet this increased need. When inadequate dietary protein is combined with chronic renal failure, patients often experience loss of lean tissue mass (muscle), muscle fiber deterioration, and decreased muscle function. The article emphasizes that the need for adequate dietary protein intake must be balanced with other aspects of the renal diet, including control of sodium, potassium, calcium, phosphorus, fluids, and in the case of patients with diabetes, simple sugars. The article briefly discusses the use of recommendations for the assessment and monitoring of patients nutritional status. The article concludes that good nutrition can prevent or reverse the effects of malnutrition, enabling patients to preserve the strength and energy they need for rehabilitation. 5 references.

Academic Periodicals covering Renal Failure Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to renal failure. In addition to these sources, you can search for articles covering renal failure that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.”

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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for renal failure. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with renal failure. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to renal failure: Amlodipine •

Systemic - U.S. Brands: Norvasc http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202670.html

Amlodipine and Benazepril •

Systemic - U.S. Brands: Lotrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203634.html

Angiotensin-Converting Enzyme (ACE) Inhibitors •

Systemic - U.S. Brands: Accupril; Aceon; Altace; Capoten; Lotensin; Mavik; Monopril; Prinivil; Univasc; Vasotec 4; Zestril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202044.html

Angiotensin-Converting Enzyme (ACE) Inhibitors and Hydrochlorothiazide •

Systemic - U.S. Brands: Accuretic; Capozide; Lotensin HCT; Prinzide; Uniretic; Vaseretic; Zestoretic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202045.html

Beta-Adrenergic Blocking Agents and Thiazide Diuretics •

Systemic - U.S. Brands: Corzide 40/5; Corzide 80/5; Inderide; Inderide LA; Lopressor HCT; Tenoretic 100; Tenoretic 50; Timolide 10-25; Ziac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202088.html

Calcium Channel Blocking Agents •

Systemic - U.S. Brands: Adalat; Adalat CC; Calan; Calan SR; Cardene; Cardizem; Cardizem CD; Cardizem SR; Dilacor-XR; DynaCirc; Isoptin; Isoptin SR; Nimotop; Plendil; Procardia; Procardia XL; Vascor; Verelan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202107.html

Candesartan •

Systemic - U.S. Brands: Atacand http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203598.html

Carvedilol •

Systemic - U.S. Brands: Coreg http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203636.html

Clonidine •

Systemic - U.S. Brands: Catapres; Catapres-TTS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202152.html

Clonidine and Chlorthalidone •

Systemic - U.S. Brands: Combipres http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202153.html

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Diuretics, Loop •

Systemic - U.S. Brands: Bumex; Edecrin; Lasix; Myrosemide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202205.html

Diuretics, Potassium-Sparing •

Systemic - U.S. Brands: Aldactone; Dyrenium; Midamor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202206.html

Diuretics, Potassium-Sparing, and Hydrochlorothiazide •

Systemic - U.S. Brands: Aldactazide; Dyazide; Maxzide; Moduretic; Spirozide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202207.html

Diuretics, Thiazide •

Systemic - U.S. Brands: Aquatensen; Diucardin; Diulo; Diuril; Enduron; Esidrix; Hydro-chlor; Hydro-D; HydroDIURIL; Hydromox; Hygroton; Metahydrin; Microzide; Mykrox; Naqua; Naturetin; Oretic; Renese; Saluron; Thalitone; Trichlorex 10; Zaroxolyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202208.html

Doxazosin •

Systemic - U.S. Brands: Cardura http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202629.html

Enalapril and Felodipine •

Systemic - U.S. Brands: Lexxel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203638.html

Eprosartan •

Systemic - U.S. Brands: Teveten http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500044.html

Guanabenz •

Systemic - U.S. Brands: Wytensin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202271.html

Guanadrel •

Systemic - U.S. Brands: Hylorel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202272.html

Guanethidine •

Systemic - U.S. Brands: Ismelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202273.html

Guanfacine •

Systemic - U.S. Brands: Tenex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202275.html

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Hydralazine and Hydrochlorothiazide •

Systemic - U.S. Brands: Apresazide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202286.html

Indapamide •

Systemic - U.S. Brands: Lozol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202296.html

Irbesartan •

Systemic - U.S. Brands: Avapro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203379.html

Losartan •

Systemic - U.S. Brands: Cozaar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202767.html

Losartan and Hydrochlorothiazide •

Systemic - U.S. Brands: Hyzaar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203639.html

Mecamylamine •

Systemic - U.S. Brands: Inversine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202340.html

Methyldopa •

Systemic - U.S. Brands: Aldomet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202359.html

Methyldopa and Thiazide Diuretics •

Systemic - U.S. Brands: Aldoclor; Aldoril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202360.html

Minoxidil •

Systemic - U.S. Brands: Loniten http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202373.html

Nisoldipine •

Systemic - U.S. Brands: Sular http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203431.html

Prazosin •

Systemic - U.S. Brands: Minipress http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202475.html

Prazosin and Polythiazide •

Systemic - U.S. Brands: Minizide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202476.html

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Rauwolfia Alkaloids •

Systemic - U.S. Brands: Harmonyl; Raudixin; Rauval; Rauverid; Serpalan; Wolfina http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202503.html

Rauwolfia Alkaloids and Thiazide Diuretics •

Systemic - U.S. Brands: Demi-Regroton; Diupres; Diurigen with Reserpine; Diutensen-R; Enduronyl; Enduronyl Forte; Oreticyl; Oreticyl Forte; Rauzide; Regroton http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202504.html

Reserpine, Hydralazine, and Hydrochlorothiazide •

Systemic - U.S. Brands: Cam-Ap-Es; Cherapas; Ser-A-Gen; Seralazide; Ser-ApEs; Serpazide; Tri-Hydroserpine; Unipres http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202506.html

Telmisartan •

Systemic - U.S. Brands: Micardis http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203710.html

Terazosin •

Systemic - U.S. Brands: Hytrin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202546.html

Torsemide •

Systemic - U.S. Brands: Demadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202740.html

Trandolapril and Verapamil •

Systemic - U.S. Brands: Tarka http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203641.html

Valsartan •

Systemic - U.S. Brands: Diovan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203478.html

Vitamin D and Related Compounds •

Systemic - U.S. Brands: Calciferol; Calciferol Drops; Calcijex; Calderol; DHT; DHT Intensol; Drisdol; Drisdol Drops; Hectorol; Hytakerol; Rocaltrol; Zemplar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202597.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

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Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to renal failure by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “renal failure” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for renal failure: •

Somatropin for Injection (trade name: Nutropin) http://www.rarediseases.org/nord/search/nodd_full?code=100

Researching Medications 265

•

Anaritide acetate (trade name: Auriculin) http://www.rarediseases.org/nord/search/nodd_full?code=558

•

Calcium acetate (trade name: Phos-Lo) http://www.rarediseases.org/nord/search/nodd_full?code=606

•

Alpha-melanocye stimulating hormone http://www.rarediseases.org/nord/search/nodd_full?code=842

•

Alpha-melanocyte stimulating hormone http://www.rarediseases.org/nord/search/nodd_full?code=875

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “renal failure” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 92697 831 917 225 1578 96248

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “renal failure” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Renal Failure In the following section, we will discuss databases and references which relate to the Genome Project and renal failure. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “renal failure” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for renal failure: •

Nephrolithiasis, X-linked Recessive, with Renal Failure Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=310468

•

Renal Failure, Progressive, with Hypertension Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=161900 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “renal failure” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “renal failure” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

23

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on renal failure can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to renal failure. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to renal failure. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “renal failure”:

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Diabetic Kidney Problems http://www.nlm.nih.gov/medlineplus/diabetickidneyproblems.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Kidney Failure http://www.nlm.nih.gov/medlineplus/kidneyfailure.html Kidney Failure http://www.nlm.nih.gov/medlineplus/tutorials/kidneyfailureloader.html Kidney Transplantation http://www.nlm.nih.gov/medlineplus/kidneytransplantation.html

Within the health topic page dedicated to renal failure, the following was listed: •

General/Overviews Dialysis Source: Merck & Co., Inc. http://www.merck.com/mrkshared/mmanual_home2/sec11/ch143/ch143d.jsp

•

Nutrition Eat Right to Feel Right on Hemodialysis http://kidney.niddk.nih.gov/kudiseases/pubs/eatright/index.htm Na-K-Phos Counter Source: American Association of Kidney Patients http://www.aakp.org/na-k-pho.htm Nutrition and Peritoneal Dialysis http://www.kidney.org/atoz/pdf/nutri_pd.pdf Protein/Calorie Counter Source: American Association of Kidney Patients http://www.aakp.org/Prot/cal.htm

•

Specific Conditions/Aspects Amyloidosis and Kidney Disease Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/amyloidosis/index.htm Anemia in Kidney Disease and Dialysis Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/anemia/index.htm Dialysis Keeps People with Kidney Failure Alive: Are You Getting Adequate Hemodialysis? http://www.medicare.gov/publications/pubs/pdf/dialysise.pdf

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Hemodialysis Dose and Adequacy Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/hemodialysisdose/ Inadequate Hemodialysis Increases the Risk of Premature Death Source: American Association of Kidney Patients http://www.aakp.org/hd-adv.htm Just the Facts: Skin and Hair Problems on Dialysis http://www.lifeoptions.org/pdfs/teachtools/skinhafs.pdf Keeping Fit: Why Dialysis Patients Should Exercise Source: American Association of Kidney Patients http://www.aakp.org/Keeping_Fit.htm Peritoneal Dialysis: Dose and Adequacy Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/peritonealdose/index.htm Preparing for Emergencies: A Guide for People on Dialysis http://www.medicare.gov/publications/pubs/pdf/10150.pdf Vascular Access for Hemodialysis Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/vascularaccess/index.htm What Do I Need to Do Before Traveling as a Dialysis Patient? Source: American Association of Kidney Patients http://www.aakp.org/Traveling.htm What You Should Know about Dialyzer Reuse: A Guide for Hemodialysis Patients and Their Families http://www.kidney.org/atoz/pdf/dialyzer_reuse.pdf •

Children Treatment Methods for Kidney Failure in Children Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/childkidneydiseases/treatment_me thods/index.htm What's the Deal with Dialysis? Source: Nemours Foundation http://kidshealth.org/kid/feel_better/things/dialysis.html

•

Law and Policy Medicare Coverage of Kidney Dialysis and Kidney Transplant Services http://www.medicare.gov/Publications/Pubs/pdf/esrdCoverage.pdf

•

Organizations Life Options Rehabilitation Program http://www.lifeoptions.org/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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National Kidney and Urologic Diseases Information Clearinghouse Source: National Institute of Diabetes and Digestive and Kidney Diseases http://kidney.niddk.nih.gov/ National Kidney Foundation http://www.kidney.org/ •

Research Hemodialysis Study Results Published Confirms Current Recommended Practice Source: National Institute of Diabetes and Digestive and Kidney Diseases http://www.nih.gov/news/pr/dec2002/niddk-18.htm Preventing Worsening Kidney Function in Patients Receiving Peritoneal Dialysis Source: American College of Physicians http://www.annals.org/cgi/content/full/139/2/I-32

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on renal failure. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Treatment Methods for Kidney Failure: Peritoneal Dialysis Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH). 2001. 24 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301)634-0716. E-mail: [email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available online at no charge; single copy free; bulk orders available. Order number: KU-153. Summary: This booklet describes the option of peritoneal dialysis (PD) as a treatment for people with advanced and permanent kidney failure (end stage renal disease or ESRD). Healthy kidneys clean the blood by removing excess fluid, minerals, and wastes. They also make hormones to keep the bones strong and the blood healthy. In kidney failure, medical treatments must be used to perform these functions of the kidneys. This booklet describes how PD works, getting ready for PD, the different types of PD, customizing PD to the individual patient, preventing problems, equipment and supplies

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for PD, testing the effectiveness of the dialysis, conditions related to kidney failure and their treatments, and the psychosocial adjustments that occur as one learns to cope with kidney failure. In PD, a soft tube (catheter) is used to fill the abdomen with dialysis solution; the peritoneum (lining of the abdomen) serves as a membrane to allow waste products and extra fluid to pass from the blood into the dialysis solution. These wastes and fluid then leave the patient's body when the dialysis solution is drained. The most common form of PD, continuous ambulatory peritoneal dialysis (CAPD), does not require a machine; other forms use a cycler to perform the exchanges. Infection is the most common problem for people on PD, but equipment advances and strict adherence to infection control measures can reduce this complication. Monitoring tests are performed on the used solution, urine, and blood measurements to determine whether the dialysis is adequate. Conditions related to kidney failure and their treatments include anemia, renal osteodystrophy (bone disease associated with kidney failure), itching (pruritus), sleep disorders, and dialysis related amyloidosis. The booklet concludes with a description of current research efforts devoted to improving treatment for patients with progressive kidney disease and permanent kidney failure. The booklet also includes a list of resources (organizations and instructional materials) and a brief description of the National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) and its contact information. 4 figures. •

Treating Kidney Failure Source: Montreal, Quebec: Kidney Foundation of Canada. 199x. [4 p.]. Contact: Available from Kidney Foundation of Canada. 300-5165, rue Sherbrooke Ouest, Montreal, QC H4A 1T6. (514) 369-4806. Fax (514) 369-2472. Website: www.kidney.ca. PRICE: Single copy free. Summary: This brochure answers questions that readers may have as they face a diagnosis of kidney failure. The brochure first reviews the physiology of the kidneys, emphasizing that kidneys remove wastes from the blood via the urine. In the early stages of chronic kidney failure, the only treatment needed may be a special diet or medication. When kidney function is no longer adequate (end stage renal disease, or ESRD), dialysis treatment or a kidney transplant is required. Dialysis is a way to clean the blood by removing wastes and excess water. The brochure describes the two types: hemodialysis and peritoneal dialysis. A kidney transplant is a surgical procedure, in which a healthy kidney from either a living or deceased donor is placed in the recipient's lower abdomen. Choosing a treatment depends on what is available in the community, as well as what is most appropriate for each individual's particular needs. The health care team can provide information and support to help the patient make a decision about the best treatment. The brochure concludes with a brief description of the Kidney Foundation of Canada, including patient services and public education programs. 5 figures.

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Choosing a Treatment for Kidney Failure Source: New York, NY: National Kidney Foundation (NKF). 1999. 15 p. Contact: Available from National Kidney Foundation (NKF). 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Website: www.kidney.org. PRICE: Single copy free; $25.00 for 100 copies. Summary: This brochure outlines the treatment options for patients with a diagnosis of kidney failure. When the kidneys are not working well, as a result of disease or injury, wastes and excess fluid build up in the blood. Treatment is instigated at this point,

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taking into consideration the patient's general medical condition, how much kidney function he or she has left, and the patient's nutritional status. The treatments for chronic kidney failure are dialysis (hemodialysis or peritoneal) and kidney transplantation. Hemodialysis is a treatment during which the blood travels through soft tubes to a dialysis machine where it goes through a special filter (dialyzer) to be cleaned. As the blood is cleaned, it is returned to the bloodstream. Only a small amount of blood is out of the body at any time. Hemodialysis requires an access (entrance) to the bloodstream; this can be a fistula, a graft, or a catheter. The brochure describes each type. In peritoneal dialysis, the blood is cleansed inside the body. The lining of the abdomen (the peritoneum) acts as a natural filter. The dialysate (cleansing solution) is passed into the belly through a catheter, wastes and excess fluid pass from the blood into the cleansing solution, and the used solution is drained from the abdomen. There are different types of peritoneal dialysis. A kidney transplant is an operation that places a healthy kidney from another person into the patient with kidney disease. The kidney may come from someone who has died (a cadaver) or from a living donor (a close relative or spouse). The patient must take medications to prevent their body from rejecting the new kidney. The brochure describes each of these treatments in some detail and considers the impact of each on the patient's diet, the use of special medications, prognosis, the role of exercise, vocational rehabilitation (returning to work), coping and psychological issues, and cost issues. The brochure concludes with a list of publications available from the National Kidney Foundation. 3 figures. •

Planning for the Treatment of Kidney Failure Source: New York, NY: National Kidney Foundation. 1994. 5 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. PRICE: Single copy free. Summary: This brochure provides information for kidney patients and their families about kidney disease and the different treatments for chronic kidney failure. Written in a question and answer format, the brochure covers topics including the role of the kidneys and the determination to start kidney replacement therapy; hemodialysis; peritoneal dialysis; kidney transplantation; receiving a transplant before going on dialysis; diet therapy and the dietary recommendations associated with each of the treatment options; drug therapy for each of the treatment options; how treatment impacts the patient's quality of life; the prognosis for regular lifespan; the role of exercise; rehabilitation to work; paying for kidney replacement treatment; and coping with kidney disease and its treatment. The brochure stresses the importance of working in close collaboration with one's physician and other members of the health care team in order to ensure the best outcome.

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Social Work Services: For the Patient with Chronic Renal Failure Source: New York, NY: National Kidney Foundation. 1991. 2 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (212) 889-2210 or (800) 622-9010. PRICE: Single copy free. Order Number 0801-PP. Summary: This brochure reviews the role of the nephrology social worker as a member of the treatment team at all transplant and dialysis facilities. Among the many services provided by the social worker are helping the patient adjust to chronic kidney disease by providing counseling to the patient and family, identifying community services, providing resources, and making referrals.

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Bone Disease in Chronic Kidney Failure Source: New York, NY: The National Kidney Foundation. 1996. [4 p.]. Contact: National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Website: www.kidney.org. PRICE: Single copy free; bulk copies available. Summary: This brochure, written in question and answer format, presents patient information about bone disease in chronic kidney failure. Topics include the causes of bone disease in people with kidney failure, the different types of bone disease, how phosphorus levels affect the bones, the role of the parathyroid glands, how aluminum levels in the bones are related to bone disease, the role of vitamin D, how diet and exercise can contribute to healthy bones, guidelines for calcium supplementation, how a kidney transplant will affect bone disease problems, and risk factors for bone disease. The brochure concludes with a list of patient education publications available from the National Kidney Foundation.

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Acute Renal Failure Source: in Kerestes-Smith, J.; Chua, G.; Sullivan, K. Guidelines for Nutritional Care. Ann Arbor, MI: Food and Nutrition Services, University of Michigan Medical Center. 1995. Chapter 53, p. 53.1-53.4. Contact: Available from Guidelines for Nutritional Care. Food and Nutrition Services, 2C227-0056, University of Michigan Hospitals, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0056. (313) 936-5199. Fax (313) 936-5195. PRICE: $79.00 including shipping and handling (as of 1996). ISBN: 0964799405. Summary: This chapter on dietary recommendations for individuals with acute renal failure (ARF) is from a manual of the impact nutrition has on promoting health and in preventing and treating disease. Included are sections detailing indications for use, contraindications, a description of the diet including a brief physiological and/or biochemical rationale, guidelines for nutritional management, nutrient adequacy, ordering procedures, and references for both the health care providers and the layperson. 1 table. 19 references.

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Financial Help for Treatment of Kidney Failure Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH). 2001. 4 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301)634-0716. E-mail: [email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available online at no charge; single copy free; bulk orders available. Order number: KU-147. Summary: This fact sheet describes the types of financial assistance available for the treatment of chronic kidney failure (end stage renal disease, or ESRD). In 1972, Congress passed legislation making people of any age with permanent kidney failure eligible for Medicare, a program that helps people over 65 and people with disabilities pay for medical care, usually up to 80 percent. Other public and private resources can help with the remaining 20 percent of the costs. The fact sheet encourages readers to consult with dialysis or transplant center social workers who can help patients locate and apply for financial assistance. The fact sheet details how Medicare works, the role of

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private insurance, Medicaid, benefits available through the Department of Veterans Affairs (VA), Social Security Disability Income (SSDI) and Supplemental Security Income (SSI) programs, and patient assistance programs from prescription drug companies. The fact sheet includes a list of resource organizations for more information, a few resources for additional reading (with availability details), and a brief description of the National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) and its contact information. 2 references. •

Renal Failure, Acute (Kidney Failure, Acute) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 395. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This fact sheet on acute renal failure is from a compilation of instructions for patients, published in book format. The fact sheet covers a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. The fact sheet can be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.

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Renal Failure, Chronic (Kidney Failure, Chronic) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 396. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This fact sheet on chronic kidney failure is from a compilation of instructions for patients, published in book format. The fact sheet covers a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. The fact sheet can be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.

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Accelerating Recovery From Acute Renal Failure: News Briefings for Science Writers on Transplantation, Dialysis and Kidney Research (memorandum) Source: New York, NY: National Kidney Foundation, Inc. March 26-27, 1990. 5 p. Contact: Available from National Kidney Foundation, Inc. 30 East 33rd Street, New York, NY 10016. (800) 622-9010 or (212) 889-2210. Summary: This technical paper prepared for the National Kidney Foundation's 1990 science writers news briefing on transplantation, dialysis, and kidney/urology research discusses ways to accelerate recovery from acute renal failure. The paper reports on recent work demonstrating that a single dose of two growth factors to animals whose

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kidneys have been severely damaged, either from ischemia or administered toxins, substantially accelerates the repair of damaged kidney tissue and leads to accelerated recovery of kidney function. The two growth factors are epidermal growth factor and transforming growth factor-alpha. This finding is the initial demonstration that certain growth factors can accelerate the repair of injured tissue in a visceral organ, similar to recent clinical and experimental demonstrations that various growth factors can speed the repair of cutaneous wounds. Clinical use of growth factors to speed the regenerative repair of damaged kidney tissue will have the potential to limit hospital length of stay, minimize expensive dialytic therapy, or diminish mortality rates. The use of growth factors during the harvesting process for kidneys for transplantation may also lessen the rate of acute kidney failure following transplantation to a recipient. •

Facts About Kidney Failure: A Guide for Employers Source: New York, NY: National Kidney Foundation. 1999. 3 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, Suite 1100, New York, NY 10016. (800) 622-9010 or (212) 889-2210. Fax (212) 689-9261. E-mail: [email protected]. Website: www.kidney.org. PRICE: Single copy free; bulk copies available. Summary: Treatments such as dialysis and kidney transplantation enable people with kidney failure to live normal lives, including working. Working is very important because it makes people feel valuable to their families, to society, and to themselves. This publication, one in a series developed to help the members of the renal (kidney) treatment team better understand all aspects of ESRD patient rehabilitation and increase their involvement in rehabilitation, focuses on the role of the employer. The brochure answers questions about kidney failure and demonstrates that an employee with kidney failure can be a valuable worker who contributes to the organization. The brochure reminds readers that Medicare helps pay for the cost of treating kidney failure regardless of the employee's age; Medicare becomes the primary payer 30 months after the employee becomes eligible for Medicare. Employers are reassured that studies have shown that employees with kidney failure are no different from other employees with regard to attendance, conscientiousness, and productivity. Employees who choose hemodialysis or peritoneal dialysis may need a temporary reduction of hours while they are getting used to their new home. The brochure outlines strategies for accommodating employees with kidney failure, the benefits (tax credits) that may be available, and laws that cover employment of people with kidney failure. A list of publications from the National Kidney Foundation (NKF) is offered, with a brief description of the organization and its activities.

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EPO: Treating Anemia in Chronic Renal Failure Source: New York, NY: National Kidney Foundation. 1990. 4 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. PRICE: Single copy free ($12 per 100 copies). Order Number 08-75. Summary: Written in a question-and-answer format, this brochure provides basic information about the use of erythropoietin (EPO) in treating the anemia frequently resulting from chronic renal failure. Topics covered include the development of kidney disease, obtaining and using EPO, dosage information, complications and side effects of EPO, and the impact of EPO on the daily lifestyle of the patient. The brochure notes that rehabilitation and adjustment to kidney failure require hard work, determination, and

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close cooperation between patient and doctor. EPO can be an important adjunct to successfully living with chronic renal failure. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “renal failure” (or synonyms). The following was recently posted: •

Screening for type 2 diabetes mellitus in adults: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2003 Feb); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3523&nbr=2749&a mp;string=renal+AND+failure

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Secondary prevention of coronary heart disease following myocardial infarction. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 January; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2303&nbr=1529&a mp;string=renal+AND+failure

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Smallpox vaccination and adverse reactions. Guidance for clinicians Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 January 24; 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3597&nbr=2823&a mp;string=renal+AND+failure

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Specialty referral guidelines for cardiovascular evaluation and management Source: American Healthways, Inc - Public For Profit Organization; 2002; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3168&nbr=2394&a mp;string=renal+AND+failure

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Specialty referral guidelines for people with diabetes Source: American Healthways, Inc - Public For Profit Organization; 1998 (revised 1999); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2005&nbr=1231&a mp;string=kidney+AND+failure

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Spondylolysis, lytic spondylolisthesis and degenerative spondylolisthesis (SLD). In: North American Spine Society phase III clinical guidelines for multidisciplinary spine care specialists Source: North American Spine Society - Medical Specialty Society; 2000; 106 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2804&nbr=2030&a mp;string=renal+AND+failure

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Standards of medical care for patients with diabetes mellitus Source: American Diabetes Association - Professional Association; 1988 (revised 2002 October; republished 2003 Jan); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3567&nbr=2793&a mp;string=renal+AND+failure

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Systemic lupus erythematosus (SLE) Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3390&nbr=2616&a mp;string=renal+AND+failure

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The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children Source: American Academy of Pediatrics - Medical Specialty Society; 1999 April 5; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1838&nbr=1064&a mp;string=renal+AND+failure

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The management of diabetes mellitus in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 December; 147 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2583&nbr=1809&a mp;string=renal+AND+failure

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The role of calcium in peri- and postmenopausal women: consensus opinion of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2001 March; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2740&nbr=1966&a mp;string=kidney+AND+failure

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The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1997 (revised 2003 May 21); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3744&nbr=2970&a mp;string=renal+AND+failure

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Thrombocytopenia Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3393&nbr=2619&a mp;string=renal+AND+failure

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Treatment of acute myocardial infarction Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 May (revised 2002 Nov); 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3659&nbr=2885&a mp;string=renal+AND+failure

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Treatment of tuberculosis Source: American Thoracic Society - Medical Specialty Society; 2003 June 20; 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3829&nbr=3054&a mp;string=renal+AND+failure

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Type 2 diabetes practice guidelines Source: International Diabetes Center - Private Nonprofit Organization; 2000 (revised 2003); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4159&nbr=3187&a mp;string=kidney+AND+failure

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Ultrasonographic examinations: indications and preparation of the patient Source: Finnish Medical Society Duodecim - Professional Association; 2000 April 18 (revised 2001 October 24); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3385&nbr=2611&a mp;string=kidney+AND+failure

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Unremitting low back pain. In: North American Spine Society phase III clinical guidelines for multidisciplinary spine care specialists Source: North American Spine Society - Medical Specialty Society; 2000; 96 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2805&nbr=2031&a mp;string=renal+AND+failure

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Use of antibiotics in adults Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2000 April; 78 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3434&nbr=2660&a mp;string=renal+AND+failure

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Use of antibiotics in paediatric care Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 March; 109 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3436&nbr=2662&a mp;string=renal+AND+failure

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Venous thromboembolism Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 June (revised 2003 Apr); 93 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3757&nbr=2983&a mp;string=kidney+AND+failure

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VHA/DoD clinical practice guideline for the management of substance use disorders Source: Department of Defense - Federal Government Agency [U.S.]; 2001 September; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3169&nbr=2395&a mp;string=renal+AND+failure

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(1) Part I. Guidelines for the management of severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury. (2) Update notice. Guidelines for the management of severe traumatic brain injury: cerebral perfusion pressure Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000 (revised 2003); 165 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3794&nbr=3020&a mp;string=renal+AND+failure

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(1) Targeted tuberculin testing and treatment of latent tuberculosis infection Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 June 9 (addendum released 2003 August 8); 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4004&nbr=3134&a mp;string=renal+AND+failure

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2002 national guideline on the management of sexually acquired reactive arthritis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3045&nbr=2271&a mp;string=kidney+AND+failure

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A guideline for the management of heart failure Source: National Heart Foundation of New Zealand - Disease Specific Society; 1996 (revised 2001 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3309&nbr=2535&a mp;string=renal+AND+failure

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ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperati Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 March 15 (revised 2002); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3149&nbr=2375&a mp;string=renal+AND+failure

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ACC/AHA guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery) Source: American College of Cardiology Foundation - Medical Specialty Society; 1999 October; 80 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2121&nbr=1347&a mp;string=renal+AND+failure

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ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines). A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Perc Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 June; 66 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2840&nbr=2066&a mp;string=renal+AND+failure

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ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evalua Source: American College of Cardiology Foundation - Medical Specialty Society; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3114&nbr=2340&a mp;string=renal+AND+failure

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ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guide Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 October; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2968&nbr=2194&a mp;string=renal+AND+failure

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ACR Appropriateness Criteriatm for percutaneous nephrostomy Source: American College of Radiology - Medical Specialty Society; 2002; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3560&nbr=2786&a mp;string=renal+AND+failure

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Acute pain management Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1997 (revised 1999 April 6); 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1888&nbr=1114&a mp;string=kidney+AND+failure

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Altered nutritional status Source: American Medical Directors Association - Professional Association; 2001; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3304&nbr=2530&a mp;string=renal+AND+failure

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American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1998 (revised 2003); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3726&nbr=2952&a mp;string=renal+AND+failure

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American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2003 Sep-October; 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4265&nbr=3265&a mp;string=renal+AND+failure

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American Gastroenterological Association medical position statement: parenteral nutrition Source: American Gastroenterological Association - Medical Specialty Society; 2001 May 18; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3056&nbr=2282&a mp;string=renal+AND+failure

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Antithrombotic therapy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 March; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2907&nbr=2133&a mp;string=renal+AND+failure

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Appropriate patient preparation for renal replacement therapy Source: Renal Physicians Association - Medical Specialty Society; 2002 October; 78 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3591&nbr=2817&a mp;string=renal+AND+failure

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ASHP therapeutic guidelines on stress ulcer prophylaxis Source: American Society of Health-System Pharmacists - Professional Association; 1999 February 15; 33 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1745&nbr=971&am p;string=renal+AND+failure

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Assessment and management of acute pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2000 October (revised 2002 Oct); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3500&nbr=2726&a mp;string=kidney+AND+failure

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Cardiovascular disease in women: a guide to risk factor screening, prevention and management Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3487&nbr=2713&a mp;string=renal+AND+failure

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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=renal+AND+failure

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Chronic kidney disease (non-dialysis) medical nutrition therapy protocol Source: American Dietetic Association - Professional Association; 2002 May; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3293&nbr=2519&a mp;string=renal+AND+failure

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Clinical practice guideline for the management of rheumatoid arthritis Source: Advanced Research Techniques in the Health Services - Private For Profit Research Organization; 2001; 170 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3683&nbr=2909&a mp;string=renal+AND+failure

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Clinical practice guideline on shared decision-making in the appropriate initiation of and withdrawal from dialysis Source: American Society of Nephrology - Professional Association; 2000 January; 124 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2195&nbr=1421&a mp;string=renal+AND+failure

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Clinical practice guidelines for nutrition in chronic renal failure Source: National Kidney Foundation - Disease Specific Society; 2000 June; 121 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2545&nbr=1771&a mp;string=renal+AND+failure

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Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3170&nbr=2396&a mp;string=renal+AND+failure

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Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3171&nbr=2397&a mp;string=renal+AND+failure

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Congestive heart failure in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jan); 71 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3165&nbr=2391&a mp;string=renal+AND+failure

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Control of pain in patients with cancer. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 June; 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2910&nbr=2136&a mp;string=renal+AND+failure

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Depression in older adults Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3512&nbr=2738&a mp;string=kidney+AND+failure

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Diagnosis and management of hypertension in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 May; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2579&nbr=1805&a mp;string=renal+AND+failure

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Diagnosis and treatment of autoimmune hepatitis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2002 August; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3447&nbr=2673&a mp;string=kidney+AND+failure

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Diagnosis and treatment of heart failure due to left ventricular systolic dysfunction. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 February; 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2906&nbr=2132&a mp;string=renal+AND+failure

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Essential hypertension Source: University of Michigan Health System - Academic Institution; 1997 (revised 2002 Aug); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3539&nbr=2765&a mp;string=renal+AND+failure

•

Evidence based clinical practice guideline for patients 6 years of age or less with a first time acute urinary tract infection (UTI) Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1999 March 28 http://www.guideline.gov/summary/summary.aspx?doc_id=1970&nbr=1196&a mp;string=renal+AND+failure

•

Genetic counseling for fragile X syndrome: recommendations of the National Society of Genetic Counselors Source: National Society of Genetic Counselors; 2000; 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2546&nbr=1772&a mp;string=kidney+AND+failure

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Glomerulonephritis Source: National Committee on Renal Care (Singapore); 2001 October; 132 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2971&nbr=2197&a mp;string=renal+AND+failure

•

Guideline for the management of acute and chronic pain in sickle cell disease Source: American Pain Society - Professional Association; 1999 August; 96 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2621&nbr=1847&a mp;string=renal+AND+failure

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•

Guidelines for quality standards for immunization Source: Infectious Diseases Society of America - Medical Specialty Society; 1997 (revised 2002); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3412&nbr=2638&a mp;string=renal+AND+failure

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Guidelines for referral to pediatric surgical specialists Source: American Academy of Pediatrics - Medical Specialty Society; 2002 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3420&nbr=2646&a mp;string=renal+AND+failure

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Guidelines for the diagnosis and management of blunt aortic injury Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2676&nbr=1902&a mp;string=renal+AND+failure

•

Guidelines for the diagnosis and treatment of chronic heart failure Source: European Society of Cardiology - Medical Specialty Society; 2001 September; 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2976&nbr=2202&a mp;string=renal+AND+failure

•

Guidelines on diagnosis and management of acute pulmonary embolism Source: European Society of Cardiology - Medical Specialty Society; 2000 August; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2592&nbr=1818&a mp;string=renal+AND+failure

•

Heart failure Source: American Medical Directors Association - Professional Association; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3303&nbr=2529&a mp;string=renal+AND+failure

•

Heart failure - systolic dysfunction Source: University of Michigan Health System - Academic Institution; 1999 August; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2282&nbr=1508&a mp;string=renal+AND+failure

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Heart Failure Society of America guidelines for management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches Source: Heart Failure Society of America, Inc - Disease Specific Society; 1999 December; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2736&nbr=1962&a mp;string=renal+AND+failure

•

Heparin and low molecular weight heparin. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2722&nbr=1948&a mp;string=renal+AND+failure

•

Herniated disc. In: North American Spine Society phase III clinical guidelines for multidisciplinary spine care specialists Source: North American Spine Society - Medical Specialty Society; 2000; 104 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2803&nbr=2029&a mp;string=renal+AND+failure

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Hyperglycemic crises in diabetes Source: American Diabetes Association - Professional Association; 2000 October (revised 2001; republished 2004 Jan); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4694&nbr=3428&a mp;string=renal+AND+failure

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Hyperlipidemia medical nutrition therapy protocol Source: American Dietetic Association - Professional Association; 2001 June; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3295&nbr=2521&a mp;string=renal+AND+failure

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Hypertension Source: National Committee on Cardiac Care (Singapore) - National Government Agency [Non-U.S.]; 2000 December; 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2837&nbr=2063&a mp;string=renal+AND+failure

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Hypertension Source: University of Texas Medical Branch Correctional Managed Care - Academic Institution; 1997 March (revised 2002 Apr); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3475&nbr=2701&a mp;string=renal+AND+failure

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Hypertension diagnosis and treatment Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 June (revised 2003 Apr); 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3759&nbr=2985&a mp;string=renal+AND+failure

•

Hypertension in older people. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2001 January; 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2915&nbr=2141&a mp;string=renal+AND+failure

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Immunizations Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 May (revised 2002 Jun); 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3353&nbr=2579&a mp;string=renal+AND+failure

•

Intravenous immunoglobulin preparations Source: University HealthSystem Consortium - Private Nonprofit Organization; 1999 March; 216 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1976&nbr=1202&a mp;string=renal+AND+failure

•

K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Source: National Kidney Foundation - Disease Specific Society; 2002 February; 246 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3192&nbr=2418&a mp;string=renal+AND+failure

•

Low back pain or sciatica in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 May; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2578&nbr=1804&a mp;string=kidney+AND+failure

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Management of acute coronary syndromes in patients presenting without persistent ST- segment elevation Source: European Society of Cardiology - Medical Specialty Society; 2000 September (revised 2002 Dec); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3518&nbr=2744&a mp;string=renal+AND+failure

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Management of acute myocardial infarction in patients presenting with ST-segment elevation Source: European Society of Cardiology - Medical Specialty Society; 1996 (revised 2003); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3590&nbr=2816&a mp;string=renal+AND+failure

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Management of chronic kidney disease and pre-ESRD in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 2000 November; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3099&nbr=2325&a mp;string=renal+AND+failure

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Management of diabetes. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2001 November; 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3078&nbr=2304&a mp;string=renal+AND+failure

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Management of early rheumatoid arthritis. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 December; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2914&nbr=2140&a mp;string=renal+AND+failure

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Management of postmenopausal osteoporosis: position statement of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2002 March; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3179&nbr=2405&a mp;string=kidney+AND+failure

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Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=renal+AND+failure

•

Massachusetts guidelines for adult diabetes care Source: Massachusetts Department of Public Health, Bureau of Family and Community Health, Diabetes Control Program - State/Local Government Agency [U.S.]; 1999 June (revised 2001 Jun); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3429&nbr=2655&a mp;string=renal+AND+failure

•

Multiple myeloma (MM) Source: Finnish Medical Society Duodecim - Professional Association; 2001 December 27; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3394&nbr=2620&a mp;string=renal+AND+failure

•

National High Blood Pressure Education Program: Working Group report on high blood pressure in pregnancy Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1990 (revised 2000 Jul); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1478&nbr=704&am p;string=renal+AND+failure

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NKF-K/DOQI clinical practice guidelines for anemia of chronic kidney disease: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 67 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2784&nbr=2010&a mp;string=renal+AND+failure

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NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2781&nbr=2007&a mp;string=renal+AND+failure

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NKF-K/DOQI clinical practice guidelines for peritoneal dialysis adequacy: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 72 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2782&nbr=2008&a mp;string=renal+AND+failure

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NKF-K/DOQI clinical practice guidelines for vascular access: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2783&nbr=2009&a mp;string=renal+AND+failure

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Osteoporosis: prevention and treatment Source: University of Michigan Health System - Academic Institution; 2002 March; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3541&nbr=2767&a mp;string=renal+AND+failure

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Pancreas transplantation in type 1 diabetes Source: American Diabetes Association - Professional Association; 1999 November (republished 2004 Jan); 1 page http://www.guideline.gov/summary/summary.aspx?doc_id=4695&nbr=3429&a mp;string=kidney+AND+failure

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Perioperative blood transfusion for elective surgery. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2001 October; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3077&nbr=2303&a mp;string=renal+AND+failure

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Practice guideline for evaluation of fever and infection in long-term care facilities Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 September; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2664&nbr=1890&a mp;string=kidney+AND+failure

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•

Practice guideline for the treatment of patients with bipolar disorder (revision) Source: American Psychiatric Association - Medical Specialty Society; 1994 December (revised 2002 Apr); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3302&nbr=2528&a mp;string=kidney+AND+failure

•

Practice guideline for the treatment of patients with eating disorders Source: American Psychiatric Association - Medical Specialty Society; 1993 (updated 2000 Jan); 51 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2194&nbr=1420&a mp;string=kidney+AND+failure

•

Practice management guidelines for geriatric trauma. Source: Eastern Association for the Surgery of Trauma - Professional Association; 2001; 55 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2959&nbr=2185&a mp;string=renal+AND+failure

•

Preventing falls in acute care Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3510&nbr=2736&a mp;string=renal+AND+failure

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Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 October. 6; 37 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2568&nbr=1794&a mp;string=renal+AND+failure

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Prevention and management of pain and stress in the neonate Source: American Academy of Pediatrics - Medical Specialty Society; 2000 February; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2597&nbr=1823&a mp;string=renal+AND+failure

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Prevention of constipation in the older adult population Source: Registered Nurses Association of Ontario - Professional Association; 2002 January; 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3710&nbr=2936&a mp;string=renal+AND+failure

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Primary care guidelines for the management of core aspects of diabetes care Source: New Zealand Guidelines Group - Private Nonprofit Organization; 2000 June; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3110&nbr=2336&a mp;string=renal+AND+failure

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Procedure guideline for radionuclide cystography in children Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1356&nbr=614&am p;string=renal+AND+failure

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Prophylaxis for patients who have experienced a myocardial infarction: drug treatment, cardiac rehabilitation and dietary manipulation Source: University of Newcastle upon Tyne, Centre for Health Services Research Academic Institution; 2001 April 23; 115 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2954&nbr=2180&a mp;string=renal+AND+failure

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Prophylaxis of venous thromboembolism. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 October; 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3485&nbr=2711&a mp;string=kidney+AND+failure

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Pulmonary rehabilitation Source: American Association for Respiratory Care - Professional Association; 2002; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3211&nbr=2437&a mp;string=renal+AND+failure

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Recommendations for preventing transmission of infections among chronic hemodialysis patients Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2001 April; 46 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2789&nbr=2015&a mp;string=renal+AND+failure

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Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update Source: American College of Rheumatology - Medical Specialty Society; 2000 September; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2935&nbr=2161&a mp;string=renal+AND+failure

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Reduction of the influenza burden in children Source: American Academy of Pediatrics - Medical Specialty Society; 2002 December; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3527&nbr=2753&a mp;string=renal+AND+failure Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Financial Help for Treatment of Kidney Failure Summary: Provides an overview of financial help that may be available for the treatment of kidney failure: Medicare, Medicaid, private insurance, VA, SSDI, and SSI benefits. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6506

•

Kidney Failure Glossary Summary: This glossary defines words that are often used when people talk or write about kidney failure and its treatments. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6517

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•

Kidney Failure: Choosing a Treatment That's Right for You Summary: Thorough description, with illustrations, of hemodialysis, peritoneal dialysis, kidney transplantation, and refusal of or withdrawal from treatment. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6518

•

Treatment Methods for Kidney Failure: Hemodialysis Summary: Describes how hemodialysis works, how people prepare for it, and the equipment and tests involved. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6540

•

Treatment Methods for Kidney Failure: Peritoneal Dialysis Summary: Describes how peritoneal dialysis works, how people prepare for it, and the equipment and tests involved. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6541

•

Treatment Methods for Kidney Failure: Transplantation Summary: This fact sheet explains how transplantation works, the process itself, posttransplant care, financial issues, and organ donation. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6543 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to renal failure. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to renal failure. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with renal failure. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about renal failure. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “renal failure” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received

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your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “renal failure”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “renal failure” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “renal failure” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.25

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

25

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)26: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

26

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

314 Renal Failure

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

315

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

317

RENAL FAILURE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acid-Base Equilibrium: The balance between acids and bases in the blood plasma. Normally it results in a slightly alkaline state with an excess of hydroxyl ions in comparison to hydrogen. The balance is achieved by the offset of the ingestion and production of acidic and basic material by the amount of acidic and basic material metabolized and excreted by the body. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acidosis, Renal Tubular: A rare sometimes familial disorder of the renal tubule

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characterized by the inability to excrete urine of normal acidity. This leads to a hyperchloremic acidosis which is often associated with one or more secondary complications such as hypercalcinuria with nephrolithiasis and nephrocalcinosis, rickets, or osteomalacia and severe potassium depletion. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a

Dictionary 319

wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Afferent Pathways: Nerve structures through which impulses are conducted from a peripheral part toward a nerve center. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the

320 Renal Failure

preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically

Dictionary 321

identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amikacin: A broad-spectrum antibiotic derived from kanamycin. It is reno- and ototoxic like the other aminoglycoside antibiotics. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Aminophylline: A drug combination that contains theophylline and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium

322 Renal Failure

channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and

Dictionary 323

stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiodysplasia: Degenerative, acquired lesions consisting of distorted, dilated, thin-walled vessels lined by vascular endothelium. This pathological state is seen especially in the gastrointestinal tract and is frequently a cause of upper and lower gastrointestinal hemorrhage in the elderly. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Angiotensin I: The decapeptide precursor of angiotensin II, generated by the action of renin on angiotensinogen. It has limited pharmacologic activity. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Angiotensins: Oligopeptides ranging in size from angiotensin precursors with 14 amino acids to the active vasoconstrictor angiotensin II with 8 amino acids, or their analogs or derivatives. The amino acid content varies with the species and changes in that content

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produce antagonistic or inactive compounds. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthropometric measurements: Measurements of human body height, weight, and size of component parts, including skinfold measurement. Used to study and compare the relative proportions under normal and abnormal conditions. [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Anticardiolipin: Antiphospholipid antibodies found in association with systemic lupus erythematosus (lupus erythematosus, systemic), antiphospholipid syndrome, and in a variety of other diseases as well as in healthy individuals. The antibodies are detected by solid-phase immunoassay employing the purified phospholipid antigen cardiolipin. [NIH] Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome, related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH]

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Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (antibodies, antiphospholipid). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (antibodies, anticardiolipin). Present also are high levels of lupus anticoagulant (lupus coagulation inhibitor). [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU]

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Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Anti-Ulcer Agents: Various agents with different action mechanisms used to treat or ameliorate ulcers or irritation of the gastrointestinal tract. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appetite Stimulants: Agents that are used to stimulate appetite. These drugs are frequently used to treat anorexia associated with cancer and AIDS. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the

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interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avidin: A specific protein in egg albumin that interacts with biotin to render it unavailable to mammals, thereby producing biotin deficiency. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Vein: The venous trunk of the upper limb; a continuation of the basilar and brachial veins running from the lower border of the teres major muscle to the outer border of the first rib where it becomes the subclavian vein. [NIH] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH]

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Backcross: A cross between a hybrid and either one of its parents. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Pair Mismatch: The presence of an uncomplementary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA (nucleic acid heteroduplexes). [NIH] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene

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causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and

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protein structure function analysis and prediction. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH]

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Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU]

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Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchopneumonia: A name given to an inflammation of the lungs which usually begins in the terminal bronchioles. These become clogged with a mucopurulent exudate forming consolidated patches in adjacent lobules. The disease is frequently secondary in character, following infections of the upper respiratory tract, specific infectious fevers, and debilitating diseases. In infants and debilitated persons of any age it may occur as a primary affection. Called also bronchial pneumonia, bronchiolitis, bronchoalveolitis, bronchopneumonitis, catarrhal pneumonia, lobular pneumonia, capillary bronchitis and vesicular bronchiolitis. [EU]

Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadaver: A dead body, usually a human body. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH]

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Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calciphylaxis: Condition of induced systemic hypersensitivity in which tissues respond to appropriate challenging agents with a sudden local calcification. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH]

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Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capital Financing: Institutional funding for facilities and for equipment which becomes a part of the assets of the institution. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbenicillin: Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiolipins: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal syphilis serodiagnosis. [NIH]

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Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of

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reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cefaclor: Semisynthetic, broad-spectrum antibiotic derivative of cephalexin. [NIH] Cefoxitin: Semisynthetic cephamycin antibiotic resistant to beta-lactamase. [NIH] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH]

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Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH]

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Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH]

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Chondrocytes: Polymorphic cells that form cartilage. [NIH] Choriocarcinoma: A malignant tumor of trophoblastic epithelium characterized by secretion of large amounts of chorionic gonadotropin. It usually originates from chorionic products of conception (i.e., hydatidiform mole, normal pregnancy, or following abortion), but can originate in a teratoma of the testis, mediastinum, or pineal gland. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]

Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH]

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CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clitoral: Pertaining to the clitoris. [EU] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties

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and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colonic Polyps: Pedunculated or sessile growths arising from the mucous membrane of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compacta: Part of substantia nigra. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols

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C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH]

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Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]

Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group.

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[NIH]

Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vasospasm: Spasm of the large- or medium-sized coronary arteries. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic

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hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Crystalluria: The excretion of crystals in the urine, producing renal irritation. [EU] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active

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aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH]

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Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU]

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Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextrorotatory: Turning towards the right hand. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar

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moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [NIH] Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to didanosine (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietetics: The study and regulation of the diet. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important

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determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH]

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Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenitis: An irritation of the first part of the small intestine (duodenum). [NIH] Duodenum: The first part of the small intestine. [NIH] Dysgerminoma: A malignant ovarian neoplasm, thought to be derived from primordial germ cells of the sexually undifferentiated embryonic gonad. It is the counterpart of the classical seminoma of the testis, to which it is both grossly and histologically identical. Dysgerminomas comprise 16% of all germ cell tumors but are rare before the age of 10, although nearly 50% occur before the age of 20. They are generally considered of low-grade malignancy but may spread if the tumor extends through its capsule and involves lymph nodes or blood vessels. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1646 [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysmenorrhoea: Painful menstruation. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH]

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Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embolectomy: Surgical removal of an obstructing clot or foreign material which has been transported from a distant vessel by the bloodstream. Removal of a clot at its original site is called thrombectomy. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until

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it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH]

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Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner

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as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and

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mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by

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determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH]

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Fat: Total lipids including phospholipids. [NIH] Fat Body: A nutritional reservoir of fatty tissue found mainly in insects and amphibians. [NIH]

Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fenoldopam: A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation

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emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Flutter: A rapid vibration or pulsation. [EU] Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of microfilaments terminate and attach to the transmembrane linkers, integrins, which in turn attach through their extracellular domains to extracellular matrix proteins. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH]

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Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Bypass: Surgical procedure in which the stomach is transected high on the body. The resulting proximal remnant is joined to a loop of the jejunum in an end-to-side anastomosis. This procedure is used frequently in the treatment of morbid obesity. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes

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are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Germfree: Free from all living micro-organisms. [NIH]

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Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after

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ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadal Dysgenesis: Any of several developmental anomalies involving the total or partial failure of the indifferent embryonic gonad to differentiate into ovary or testis. This concept includes gonadal agenesis. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH]

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Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haematuria: Blood in the urine. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU]

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Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Heat Stroke: A condition characterized by cessation of sweating, hot dry skin, delirium, collapse, and coma and resulting from prolonged exposure to high environmental temperature. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by

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centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic tissue: Tissue in which new blood cells are formed. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodialyzer: Apparatus for hemodialysis performing the functions of human kidneys in place of the damaged organs; highly specialized medical equipment used for treating kidney failure by passing the body's toxic substances through an external artificial kidney. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemoperfusion: Removal of toxins or metabolites from the circulation by the passing of blood, within a suitable extracorporeal circuit, over semipermeable microcapsules containing adsorbents (e.g., activated charcoal) or enzymes, other enzyme preparations (e.g.,

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gel-entrapped microsomes, membrane-free enzymes bound to artificial carriers), or other adsorbents (e.g., various resins, albumin-conjugated agarose). [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heteroduplex Analysis: A method of detecting gene mutation by mixing PCR-amplified mutant and wild-type DNA followed by denaturation and reannealing. The resultant products are resolved by gel electrophoresis, with single base substitutions detectable under optimal electrophoretic conditions and gel formulations. Large base pair mismatches may also be analyzed by using electron microscopy to visualize heteroduplex regions. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the

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opening. [NIH] Hirudin: The active principle in the buccal gland secretion of leeches. It acts as an antithrombin and as an antithrombotic agent. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydatidiform Mole: A trophoblastic disease characterized by hydrops of the mesenchymal portion of the villus. Its karyotype is paternal and usually homozygotic. The tumor is indistinguishable from chorioadenoma destruens or invasive mole ( = hydatidiform mole, invasive) except by karyotype. There is no apparent relation by karyotype to

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choriocarcinoma. Hydatidiform refers to the presence of the hydropic state of some or all of the villi (Greek hydatis, a drop of water). [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydronephrosis: Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroureter: Abnormal enlargement of the ureter caused by any blockage that prevents urine from draining into the bladder. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaldosteronism: Aldosteronism. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperkalaemia: Pathology: an abnormally high concentration of potassium in the blood. [EU]

Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperoxaluria: Excretion of an excessive amount of oxalate in the urine. [NIH] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor

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formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Pulmonary: Increased pressure within the pulmonary circulation, usually secondary to cardiac or pulmonary disease. [NIH] Hypertension, Renal: Hypertension due to renal diseases, especially chronic parenchymal disease. Hypertension as a result of compression or obstruction of the renal artery or its branches is hypertension, renovascular. [NIH] Hypertension, Renovascular: Hypertension due to compression or obstruction of the renal artery or its branches. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity

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against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU]

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In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and

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severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures

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and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraindividual: Being or occurring within the individual. [EU] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH]

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Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is

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attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH]

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Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Legionellosis: Infections with bacteria of the genus Legionella. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocyte Count: A count of the number of white blood cells per unit volume in venous blood. A differential leukocyte count measures the relative numbers of the different types of white cells. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils,

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and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein

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B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment

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but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated.

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[EU]

Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU]

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Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH]

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Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercuric Chloride: Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylmalonic Acid: A malonic acid derivative which is a vital intermediate in the metabolism of fat and protein. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This metabolic disease is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH]

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Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

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Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Moxalactam: Broad- spectrum beta-lactam antibiotic similar in structure to the cephalosporins except for the substitution of an oxaazabicyclo moiety for the thiaazabicyclo moiety of certain cephalosporins. It has been proposed especially for the meningitides because it passes the blood-brain barrier and for anaerobic infections. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucopurulent: Containing both mucus and pus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multidose: Occurring in, or using multiple doses. [EU] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH]

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Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH]

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Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU]

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Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephrolithiasis: Kidney stones. [NIH] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon,

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and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonmalignant: Not cancerous. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood

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pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutrition Assessment: Evaluation and measurement of nutritional variables in order to assess the level of nutrition or the nutritional status of the individual. Nutrition surveys may be used in making the assessment. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor

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of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Preservation: The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from

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arginine. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ototoxic: Having a deleterious effect upon the eighth nerve, or upon the organs of hearing and balance. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH]

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Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH]

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Pancreatectomy: Surgery to remove the pancreas. In a total pancreatectomy, a portion of the stomach, the duodenum, common bile duct, gallbladder, spleen, and nearby lymph nodes also are removed. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papovaviridae: A family of small, non-enveloped DNA viruses affecting mostly mammals. Most members can induce tumors in hosts. There are two genera: Papillomavirus and Polyomavirus. [NIH] Paralyses: Loss or impairment of muscle function or sensation. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraplegia: Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with spinal cord diseases, although brain diseases; peripheral nervous system diseases; neuromuscular diseases; and muscular diseases may also cause bilateral leg weakness. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parathyroidectomy: Excision of one or both of the parathyroid glands. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH]

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Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic fracture: A broken bone caused by disease, often by the spread of cancer to the bone. [NIH] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillinase: A beta-lactamase preferentially cleaving penicillins. (Dorland, 28th ed) EC 3.5.2.-. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Elongation Factors: Protein factors uniquely required during the elongation phase of protein synthesis. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-

Dictionary 397

L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Perioperative Care: Interventions to provide care prior to, during, and immediately after surgery. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs

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are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels,

Dictionary 399

active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [NIH] Phosphoglycerate Kinase: An enzyme catalyzing the transfer of a phosphate group from 3phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoribosyl Pyrophosphate: The key substance in the biosynthesis of histidine, tryptophan, and purine and pyrimidine nucleotides. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Piperacillin: Semisynthetic, broad-spectrum, ampicillin-derived ureidopenicillin antibiotic

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proposed for pseudomonas infections. It is also used in combination with other antibiotics. [NIH]

Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH]

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Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polydipsia: Chronic excessive thirst, as in diabetes mellitus or diabetes insipidus. [EU] Polyhydramnios: Excess of amniotic fluid greater than 2,000 ml. It is a common obstetrical complication whose major causes include maternal diabetes, chromosomal disorders, isoimmunological disease, congenital abnormalities, and multiple gestations. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH] Polyphagia: Great hunger; a sign of diabetes. People with this great hunger often lose weight. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polytetrafluoroethylene: Homopolymer of tetrafluoroethylene. Nonflammable, tough, inert plastic tubing or sheeting; used to line vessels, insulate, protect or lubricate apparatus; also as filter, coating for surgical implants or as prosthetic material. Synonyms: Fluoroflex; Fluoroplast; Ftoroplast; Halon; Polyfene; PTFE; Tetron. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH]

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Potassium Compounds: Inorganic compounds that contain potassium as an integral part of the molecule. [NIH] Potassium, Dietary: Potassium or potassium compounds used in foods or as foods. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Practice Management: Business management of medical and dental practices that may include capital financing, utilization management, and arrangement of capitation agreements with other parties. [NIH] Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH]

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Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prokinetic Drugs: Medicines that cause muscles in the GI tract to move food. An example is cisapride (SIS-uh-pryd) (Propulsid). [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane).

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The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein

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C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein-Energy Malnutrition: The lack of sufficient energy or protein to meet the body's metabolic demands, as a result of either an inadequate dietary intake of protein, intake of poor quality dietary protein, increased demands due to disease, or increased nutrient losses. [NIH]

Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]

Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudomonas Infections: Infections with bacteria of the genus Pseudomonas. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in

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psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychological Theory: Principles applied to the analysis and explanation of psychological or behavioral phenomena. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a

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wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to

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separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Transforming Growth Factor beta: Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]

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Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH]

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Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the

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retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of

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developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatica: A condition characterized by pain radiating from the back into the buttock and

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posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrub Typhus: An acute infectious disease caused by Orientia tsutsugamushi. It is limited to eastern and southeastern Asia, India, northern Australia, and the adjacent islands. Characteristics include the formation of a primary cutaneous lesion at the site of the bite of an infected mite, fever lasting about two weeks, and a maculopapular rash. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminoma: A type of cancer of the testicles. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU]

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Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shiga Toxin: A toxin produced by Shigella dysenteriae. It is the protype of class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA with peptide elongation factors. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoidal: S-shaped; shaped like the letter sigma. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-

Dictionary 415

mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol

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Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH]

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Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spondylolisthesis: Forward displacement of one vertebra over another. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sternum: Breast bone. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between

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the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Stress Ulcer: An upper GI ulcer from physical injury such as surgery, major burns, or critical head injury. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclavian Artery: Artery arising from the brachiocephalic trunk on the right side and from the arch of the aorta on the left side. It distributes to the neck, thoracic wall, spinal cord, brain, meninges, and upper limb. [NIH] Subclavian Vein: The continuation of the axillary vein which follows the subclavian artery and then joins the internal jugular vein to form the brachiocephalic vein. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH]

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Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH]

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Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Teicoplanin: Glycopeptide antibiotic complex from Actinoplanes teichomyceticus active against gram-positive bacteria. It consists of five major components each with a different fatty acid moiety. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH]

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Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermogenesis: The generation of heat in order to maintain body temperature. The uncoupled oxidation of fatty acids contained within brown adipose tissue and shivering are examples of thermogenesis in mammals. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH]

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Thrombectomy: Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]

Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate

Dictionary 423

organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Total pancreatectomy: Surgery to remove the entire pancreas. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trabecular Meshwork: A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to

424 Renal Failure

the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by

Dictionary 425

conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tube-feeding: Feeding by a tube passed into the stomach. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]

Tuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin

426 Renal Failure

specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Uranyl Nitrate: Bis(nitrato-O)dioxouranium. A compound used in photography and the porcelain industry. It causes severe renal insufficiency and renal tubular necrosis in mammals and is an effective lymphocyte mitogen. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urography: Radiography of any part of the urinary tract. [NIH] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH]

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Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasopressor: 1. Stimulating contraction of the muscular tissue of the capillaries and arteries. 2. An agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU]

VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide

428 Renal Failure

back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium

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metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar

430 Renal Failure

moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX 1 1-phosphate, 181, 317 A Abdomen, 281, 282, 317, 331, 332, 356, 375, 380, 392, 395, 396, 397, 417, 421 Abdominal, 21, 125, 232, 317, 319, 349, 375, 384, 394, 395, 397, 398, 409 Abdominal Pain, 21, 317, 398 Aberrant, 66, 193, 317 Ablation, 52, 242, 317 Abortion, 317, 325, 340, 428 Acceptor, 317, 379, 394 Acetaminophen, 27, 317 Acetic Acids, 168, 317 Acetylcholine, 205, 317, 390 Acetylcysteine, 87, 177, 250, 317 Acid-Base Equilibrium, 190, 317 Acidity, 317, 318, 398 Acidosis, 15, 16, 23, 63, 101, 112, 117, 135, 183, 217, 228, 235, 242, 243, 246, 317 Acidosis, Renal Tubular, 217, 317 Acquired Immunodeficiency Syndrome, 87, 318 Acremonium, 318, 338 Actin, 38, 41, 48, 81, 318, 385, 388, 424 Acute Disease, 75, 318 Acute myelogenous leukemia, 318 Acute myeloid leukemia, 125, 318 Acute nonlymphocytic leukemia, 318 Acute renal, 11, 12, 15, 16, 17, 20, 23, 28, 33, 36, 38, 39, 46, 48, 52, 53, 54, 55, 62, 63, 69, 71, 72, 75, 76, 82, 134, 135, 136, 137, 145, 147, 161, 162, 168, 169, 171, 173, 177, 179, 182, 183, 186, 187, 190, 192, 193, 197, 198, 202, 209, 210, 211, 219, 220, 221, 222, 227, 228, 236, 250, 251, 283, 284 Acyclovir, 107, 318 Adaptability, 318, 337 Adaptation, 26, 318 Adenine, 83, 167, 318, 329, 406 Adenosine, 62, 174, 179, 180, 210, 211, 318, 327, 333, 371, 399, 421 Adenosine Triphosphate, 318, 327, 399 Adenylate Cyclase, 175, 178, 201, 204, 318, 339 Adhesions, 48, 318 Adipocytes, 201, 319, 378

Adipose Tissue, 319, 379, 421 Adjustment, 26, 110, 142, 218, 234, 285, 318, 319 Adjuvant, 98, 319, 361 Adolescence, 319, 396 Adrenal Cortex, 237, 319, 320, 345, 346, 357, 403, 410 Adrenal Glands, 319, 322, 409 Adrenal Medulla, 319, 336, 355, 356, 390 Adrenergic, 40, 173, 184, 198, 260, 319, 325, 351, 356, 403, 420 Adrenergic beta-Antagonists, 319, 325 Adverse Effect, 77, 173, 197, 215, 253, 319, 399, 414 Aerobic, 319, 357, 372, 405 Afferent, 65, 319, 378, 416 Afferent Pathways, 65, 319 Affinity, 42, 78, 319, 320, 384, 408, 416 Agar, 319, 320, 346, 400 Agarose, 320, 368 Age of Onset, 320, 425 Agenesis, 320, 364 Agonist, 37, 62, 168, 181, 196, 320, 351, 359 Airways, 165, 320 Albumin, 12, 21, 28, 73, 179, 254, 256, 320, 328, 368, 400 Albuminuria, 22, 320 Aldehydes, 69, 320, 429 Aldosterone, 199, 217, 237, 320 Algorithms, 220, 320, 330 Alimentary, 320, 395 Alkaline, 73, 91, 241, 317, 320, 322, 334, 421 Alkaline Phosphatase, 73, 91, 241, 320 Alkaloid, 320, 335, 341, 342, 421 Alkalosis, 22, 243, 320, 421 Alleles, 45, 320, 379 Allergic Rhinitis, 200, 320, 366 Allo, 187, 320 Allogeneic, 50, 93, 97, 320, 365 Allogeneic bone marrow transplantation, 97, 320 Allograft, 77, 114, 321 Allylamine, 321 Alopecia, 321, 347 Alpha Particles, 321, 407 Alternative medicine, 252, 321

432 Renal failure

Aluminum, 134, 219, 222, 239, 283, 321, 419 Alveoli, 321, 348, 428 Alveolitis, 165, 321 Ameliorating, 162, 165, 190, 231, 321 Amenorrhea, 127, 321 Amikacin, 83, 321 Amine, 111, 128, 321, 369 Amino Acid Sequence, 321, 324, 358, 362 Aminophylline, 210, 211, 321 Amlodipine, 173, 197, 260, 321 Ammonia, 321, 322, 419, 426 Amniotic Fluid, 322, 401 Amphetamines, 322, 341 Ampicillin, 322, 399 Ampulla, 322, 355 Amputation, 150, 240, 322 Amyloidosis, 19, 91, 110, 176, 220, 278, 281, 322 Anabolic, 73, 112, 193, 322, 350 Anaemia, 94, 160, 322, 383 Anaerobic, 322, 372, 386 Anaesthesia, 89, 117, 322, 373 Anal, 322, 380, 387 Analgesic, 27, 250, 251, 317, 322, 341, 371, 377, 394 Analog, 318, 322, 360, 378 Analogous, 322, 352, 424 Anaphylatoxins, 322, 343 Anastomosis, 35, 322, 361 Anatomical, 30, 137, 322, 328, 339, 344, 350, 354, 372, 413 Androgens, 319, 322, 346 Anemic, 47, 323 Anesthesia, 37, 177, 323, 354, 389 Anesthetics, 323, 329, 356 Aneurysm, 323, 326, 427 Angina, 99, 172, 173, 180, 186, 187, 197, 198, 200, 201, 319, 322, 323, 403 Angina Pectoris, 172, 180, 186, 187, 198, 319, 322, 323, 403 Anginal, 323, 390 Angiodysplasia, 232, 323 Angiogenesis, 165, 180, 323 Angiography, 59, 104, 137, 323 Angioplasty, 114, 182, 200, 207, 254, 323, 388 Angiotensin converting enzyme inhibitor, 22, 85, 323 Angiotensin I, 62, 65, 212, 323 Angiotensin-Converting Enzyme Inhibitors, 323, 325

Angiotensinogen, 40, 71, 170, 198, 212, 323, 410 Angiotensins, 71, 323 Anhydrous, 161, 163, 164, 166, 187, 324 Animal model, 28, 30, 41, 47, 49, 61, 172, 250, 324 Anions, 320, 324, 376, 414, 419 Anomalies, 324, 364, 420 Anorexia, 73, 203, 237, 239, 256, 322, 324, 326, 393, 426 Anoxia, 38, 52, 324 Antagonism, 187, 324, 333, 350, 421 Anterior chamber, 324, 376, 423 Anthropometric measurements, 241, 324 Anthropometry, 230, 324 Antibacterial, 127, 324, 371, 416, 427 Antibiotic, 49, 61, 321, 322, 324, 332, 337, 338, 340, 377, 386, 396, 399, 412, 416, 420, 421 Antibodies, 184, 324, 325, 328, 366, 367, 369, 372, 381, 400, 407, 412 Antibodies, Anticardiolipin, 324, 325 Antibodies, Antiphospholipid, 324, 325 Antibody, 14, 151, 176, 319, 324, 325, 342, 366, 369, 372, 373, 376, 383, 386, 407, 412, 416, 429 Anticoagulant, 143, 324, 325, 404 Anticonvulsant, 325, 398 Antidepressant, 236, 325 Antidiuretic, 178, 204, 237, 325, 389 Antidote, 126, 325 Antiemetic, 232, 325 Antifungal, 325, 359 Antigen, 191, 319, 324, 325, 335, 343, 363, 369, 371, 372, 373, 374, 383 Antigen-Antibody Complex, 325, 343 Antihypertensive, 17, 39, 86, 184, 219, 325, 359, 370 Antihypertensive Agents, 184, 325 Anti-infective, 325, 370, 376 Anti-inflammatory, 27, 33, 46, 62, 64, 162, 234, 317, 325, 327, 346, 363, 371, 373, 377, 402 Anti-Inflammatory Agents, 234, 325, 327, 346 Antimetabolite, 318, 325, 333, 360, 411 Antimicrobial, 219, 325, 338 Antineoplastic, 325, 333, 346, 360, 362, 383 Antioxidant, 46, 250, 325, 394 Antiphospholipid Syndrome, 99, 324, 325 Antipyretic, 317, 325, 377 Antiseptic, 325, 384

433

Antithrombotic, 134, 292, 297, 326, 369, 404 Anti-Ulcer Agents, 135, 326 Antiviral, 317, 318, 326, 333, 375, 397, 411 Anuria, 326, 377 Anus, 322, 326, 332, 342 Anxiety, 77, 141, 175, 203, 319, 326, 391, 403 Anxiety Disorders, 175, 326 Aorta, 326, 336, 345, 409, 418, 428 Aortic Aneurysm, 94, 113, 125, 326, 361 Apolipoproteins, 235, 326, 379 Apoptosis, 36, 46, 54, 55, 64, 68, 73, 174, 193, 194, 326, 347 Appetite Stimulants, 229, 326 Applicability, 50, 326 Aqueous, 163, 326, 329, 347, 354, 370, 423 Aqueous humor, 326, 423 Arachidonic Acid, 326, 403, 404 Archaea, 326, 385 Arginine, 62, 136, 169, 180, 187, 322, 326, 390, 393, 406 Aromatic, 204, 326, 384, 398 Arrhythmia, 180, 326, 428 Arterial, 38, 95, 185, 196, 217, 242, 254, 321, 325, 327, 335, 339, 345, 371, 405, 420 Arteries, 171, 200, 253, 326, 327, 331, 345, 380, 384, 387, 400, 406, 422, 427 Arteriography, 103, 327 Arteriolar, 327, 332, 359, 410 Arterioles, 327, 331, 335, 385, 387, 427 Arteriosus, 327, 406 Arteriovenous, 36, 150, 243, 254, 327, 385 Arteriovenous Fistula, 36, 254, 327 Arteritis, 253, 327 Artery, 69, 180, 196, 245, 290 Articular, 327, 393 Artifacts, 104, 327 Aseptic, 327, 392, 417 Aspergillosis, 125, 327 Aspirin, 27, 327 Assay, 46, 49, 58, 62, 68, 73, 201, 256, 327, 412 Astringents, 327, 384 Asymptomatic, 327, 330, 395 Ataxia, 274, 275, 327, 338, 421 ATP, 38, 52, 53, 63, 174, 318, 327, 351, 362, 381, 399, 404, 405, 423 Atrial, 172, 193, 198, 291, 327, 345, 424 Atrial Fibrillation, 172, 198, 291, 327 Atrial Flutter, 172, 198, 327 Atrioventricular, 327, 345, 419

Atrioventricular Node, 327, 419 Atrium, 327, 328, 336, 345, 385, 419, 424, 428 Atrophy, 58, 274, 328, 389 Autacoids, 328, 373 Autoantibodies, 42, 116, 324, 328 Autoantigens, 328 Autodigestion, 328, 395 Autoimmune disease, 42, 324, 328, 387 Autoimmune Hepatitis, 295, 328 Autoimmunity, 77, 328 Autologous, 50, 110, 328 Autonomic, 240, 317, 328, 361, 390, 397, 416, 419 Autonomic Nervous System, 328, 397, 419 Autoradiography, 40, 328 Avidin, 46, 328 Axillary, 328, 418 Axillary Vein, 328, 418 Azotemia, 62, 171, 328, 426 B Bacillus, 328, 425 Back Pain, 288, 298, 328 Backcross, 43, 329 Bacterial Physiology, 318, 329 Bactericidal, 329, 357 Bacteriophage, 329, 400, 424 Bacterium, 329, 344, 367 Bacteriuria, 329, 426 Barbiturate, 329, 421 Basal Ganglia, 327, 329, 332, 361 Basal Ganglia Diseases, 327, 329 Base Pair Mismatch, 329, 368 Base Sequence, 206, 329, 362 Basement Membrane, 41, 48, 57, 59, 68, 329, 358, 378 Basophils, 329, 365, 378 Benign, 59, 89, 94, 200, 329, 361, 362, 366, 388, 407 Benzene, 329, 330, 376 Benzodiazepines, 178, 330 Beta blocker, 17, 330 Beta-Lactamases, 330, 372 Beta-Thalassemia, 124, 330 Bilateral, 14, 21, 86, 90, 242, 330, 395 Bile, 330, 361, 364, 368, 377, 380, 417, 419 Bile duct, 330, 361 Bile Pigments, 330, 377 Biliary, 231, 330, 334, 342, 395 Biliary Tract, 330, 334, 395 Bilirubin, 320, 330, 361, 364, 370

434 Renal failure

Bioavailability, 161, 188, 202, 219, 234, 240, 330 Biological response modifier, 330, 374 Biological therapy, 330, 365 Biomarkers, 71, 330 Biopsy, 21, 22, 34, 57, 153, 242, 330, 397 Biotechnology, 82, 85, 154, 252, 271, 273, 274, 275, 330 Biotic, 172, 331 Biotin, 46, 139, 140, 240, 328, 331 Bipolar Disorder, 302, 331 Bivalent, 331, 384 Bladder, 178, 200, 203, 331, 343, 347, 370, 373, 387, 389, 404, 409, 426 Bloating, 331, 361 Blood Cell Count, 155, 331, 367 Blood Coagulation, 331, 334, 359, 412, 422 Blood Glucose, 17, 68, 331, 367, 374 Blood Platelets, 331, 383, 414, 422 Blood transfusion, 301, 331 Blood urea, 172, 209, 241, 243, 256, 331, 377 Blood Volume, 177, 188, 331, 336 Blood-Brain Barrier, 331, 386 Blot, 42, 57, 331 Body Composition, 148, 331 Body Fluids, 320, 330, 331, 333, 352, 359, 391, 416, 425 Body Image, 40, 331 Body Mass Index, 331, 393 Bone Density, 153, 332 Bone Development, 73, 332 Bone Marrow, 90, 143, 144, 147, 170, 193, 194, 233, 237, 255, 318, 330, 332, 347, 357, 362, 365, 372, 381, 383, 386, 416, 417, 418 Bone Marrow Cells, 170, 332, 383 Bone Marrow Transplantation, 90, 147, 170, 332 Bone metastases, 227, 332 Bone scan, 332, 412 Bowel, 23, 162, 174, 200, 322, 332, 350, 373, 375, 398, 418 Bowel Movement, 332, 350, 418 Brachytherapy, 332, 375, 376, 407, 429 Bradycardia, 86, 332 Bradykinin, 332, 390, 400 Brain Diseases, 332, 395 Brain Stem, 182, 332, 338 Branch, 298, 313, 332, 381, 396, 406, 409, 416, 421

Breakdown, 31, 178, 184, 203, 331, 332, 337, 350, 361, 392 Breeding, 43, 332 Broad-spectrum, 321, 322, 332, 335, 337, 338, 399 Bromodeoxyuridine, 73, 333 Bronchi, 333, 356, 421 Bronchial, 321, 333, 369, 421 Bronchioles, 321, 333 Bronchiolitis, 333 Bronchitis, 200, 333, 340 Bronchopneumonia, 101, 333 Buccal, 333, 369, 381 Bullous, 114, 333 Burns, 12, 94, 333, 418 Burns, Electric, 333 Bypass, 127, 182, 251, 290, 333, 388 C Cachexia, 58, 162, 174, 333 Cadaver, 282, 333 Cadmium, 251, 333 Cadmium Poisoning, 333 Caffeine, 333, 406 Calcifediol, 333, 334 Calcification, 117, 129, 334 Calcineurin, 30, 334 Calcinosis, 35, 241, 334 Calciphylaxis, 117, 241, 334 Calcitonin, 32, 334 Calcitriol, 13, 32, 72, 106, 190, 334 Calcium channel blocker, 172, 184, 322, 325, 334, 428 Calcium Channel Blockers, 325, 334 Calcium Channels, 32, 334 Calcium Oxalate, 45, 334, 394 Calculi, 97, 334, 364 Calmodulin, 334, 335 Caloric intake, 18, 335 Camptothecin, 335, 376 Candidiasis, 335, 359 Capillary, 41, 59, 332, 333, 335, 363, 379, 428 Capital Financing, 335, 402 Capsules, 155, 335, 351, 361, 363 Captopril, 59, 335 Carbenicillin, 83, 335 Carbohydrate, 30, 205, 233, 335, 346, 363, 364, 401 Carboxy, 164, 335 Carcinogen, 335, 383 Carcinogenic, 330, 335, 374, 392, 403, 417 Carcinoma, 75, 335

435

Cardiac Output, 37, 335 Cardiogenic, 37, 335 Cardiolipins, 325, 335 Cardiomyopathy, 172, 198, 336 Cardiopulmonary, 88, 336 Cardiopulmonary Bypass, 88, 336 Cardioselective, 336, 403 Cardiovascular Agents, 219, 336 Cardiovascular System, 199, 207, 336 Carnitine, 87, 233, 236, 336 Carotene, 336, 410 Carrier Proteins, 336, 400 Case report, 14, 90, 100, 101, 125, 128, 336, 341 Case series, 336, 341 Catabolism, 15, 63, 68, 235, 237, 250, 336, 426 Catecholamine, 336, 351 Catheter, 89, 113, 151, 208, 281, 282, 336, 354, 376 Catheterization, 104, 171, 323, 336, 376, 388 Cations, 336, 376 Cauda Equina, 336, 413 Caudal, 336, 350, 371, 401 Causal, 337, 367, 375 Cause of Death, 26, 65, 337 Cecum, 49, 337, 378 Cefaclor, 84, 337 Cefoxitin, 83, 337 Ceftriaxone, 83, 84, 337 Cell, 20, 21, 29, 32, 33, 34, 35, 36, 38, 39, 41, 44, 46, 48, 52, 53, 54, 55, 57, 58, 60, 62, 63, 66, 68, 69, 70, 71, 75, 76, 77, 82, 88, 92, 100, 116, 141, 147, 148, 151, 152, 153, 155, 160, 170, 174, 175, 181, 184, 192, 193, 195, 199, 207, 215, 233, 237, 243, 274, 275, 295, 317, 318, 320, 322, 326, 328, 329, 330, 331, 334, 336, 337, 339, 340, 341, 343, 344, 346, 347, 348, 349, 350, 353, 354, 355, 356, 358, 360, 361, 362, 363, 365, 368, 369, 372, 374, 375, 376, 378, 383, 385, 386, 388, 390, 391, 392, 393, 398, 399, 400, 404, 408, 410, 413, 414, 418, 419, 420, 421, 422, 423, 424, 425, 427, 429 Cell Adhesion, 48, 75, 78, 116, 337, 374 Cell Adhesion Molecules, 116, 337 Cell Count, 151, 153, 155, 337 Cell Death, 46, 68, 175, 326, 337, 363 Cell Differentiation, 337, 414

Cell Division, 52, 274, 329, 337, 365, 385, 400, 413 Cell Extracts, 44, 337 Cell membrane, 181, 184, 334, 336, 337, 339, 349, 353, 399 Cell motility, 337, 368 Cell proliferation, 35, 46, 53, 64, 66, 193, 194, 207, 337, 375, 414 Cell Survival, 69, 337, 365 Cell Transplantation, 141, 148, 337 Cellobiose, 337, 338 Cellular metabolism, 184, 337 Cellulose, 15, 337, 338, 360, 400 Central Nervous System Diseases, 175, 338 Central Nervous System Infections, 338, 366 Centrifugation, 338, 367 Cephalexin, 337, 338 Cephalosporins, 218, 330, 338, 386 Ceramide, 39, 338 Cerebellar, 327, 338, 408, 424 Cerebellar Diseases, 327, 338, 424 Cerebellum, 332, 338, 401, 408 Cerebral Cortex, 327, 332, 338, 357 Cerebral hemispheres, 329, 332, 338 Cerebrospinal, 104, 338 Cerebrospinal fluid, 104, 338 Cerebrovascular, 150, 175, 329, 334, 336, 338, 421 Cerebrum, 338, 399, 425 Character, 323, 333, 339, 348 Chelating Agents, 134, 339 Chemokines, 55, 76, 339 Chemotactic Factors, 339, 343 Chemotaxis, 52, 339 Chemotherapeutic agent, 339, 350 Chemotherapy, 170, 192, 193, 238, 293, 339 Chickenpox, 14, 339 Chimera, 38, 339 Chin, 117, 339, 383 Chloride Channels, 32, 339 Chlorophyll, 339, 360 Cholera, 45, 339, 428 Cholera Toxin, 45, 339 Cholesterol, 92, 145, 235, 240, 242, 244, 330, 339, 340, 345, 352, 361, 370, 379, 380, 417 Cholesterol Esters, 339, 379 Chondrocytes, 73, 340 Choriocarcinoma, 107, 340, 370 Choroid, 340, 345, 410

436 Renal failure

Chromaffin System, 340, 354 Chromatin, 326, 340, 356 Chromium, 139, 239, 340 Chromosomal, 340, 400, 401 Chromosome, 22, 42, 43, 44, 340, 344, 379, 413 Chronic Disease, 170, 195, 333, 340, 378 Chronic Obstructive Pulmonary Disease, 194, 200, 340 Chronic renal, 12, 13, 14, 15, 18, 19, 21, 22, 23, 24, 25, 27, 28, 29, 31, 36, 41, 43, 47, 51, 54, 59, 60, 61, 67, 72, 73, 76, 78, 80, 81, 85, 134, 135, 136, 137, 148, 150, 161, 162, 164, 165, 170, 179, 180, 181, 190, 196, 201, 203, 205, 206, 208, 209, 215, 217, 218, 222, 223, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 241, 243, 244, 247, 249, 250, 253, 254, 256, 285, 293 Chylomicrons, 340, 379 Cilastatin, 85, 340, 372 Cimetidine, 135, 340 Circadian, 135, 203, 340 Circadian Rhythm, 203, 340 Circulatory system, 188, 209, 340, 354 Cirrhosis, 23, 128, 165, 168, 178, 180, 181, 203, 340 CIS, 81, 341, 411 Cisplatin, 172, 234, 341 Citric Acid, 169, 341 Citrus, 341 Clamp, 32, 341 Clear cell carcinoma, 341, 349 Clinical Medicine, 94, 116, 341, 402 Clinical study, 143, 341, 344 Clinical trial, 24, 25, 26, 35, 36, 65, 78, 143, 156, 271 Clitoral, 185, 200, 341 Clone, 32, 341 Cloning, 43, 60, 165, 170, 184, 206, 330, 341 Coagulation, 12, 71, 86, 171, 227, 325, 331, 341, 368, 400, 422 Coca, 341 Cocaine, 46, 341 Codeine, 341, 394 Coenzymes, 342, 390 Cofactor, 342, 404, 422 Cognitive restructuring, 342, 418 Colchicine, 52, 342 Colitis, 49, 174, 232, 342, 373 Collagen, 46, 53, 57, 59, 68, 73, 321, 329, 342, 344, 358, 359, 361, 400, 403

Collapse, 332, 342, 366 Colloidal, 320, 342, 353, 414 Colon, 49, 274, 342, 373, 378 Colonic Polyps, 232, 342 Colorectal, 130, 342 Colorectal Cancer, 130, 342 Combination Therapy, 17, 184, 342 Common Bile Duct, 342, 395 Comorbidity, 74, 342 Compacta, 204, 342 Complement, 153, 322, 342, 362, 374, 382, 400, 405 Compliance, 28, 77, 343 Compulsions, 343, 391 Computational Biology, 271, 273, 343 Computed tomography, 124, 332, 343, 412 Computerized tomography, 343 Concentric, 102, 343 Conception, 317, 340, 343, 359, 417 Concomitant, 48, 173, 197, 201, 343 Concretion, 334, 343 Conduction, 328, 343, 389 Cones, 343, 411 Congestion, 20, 54, 343 Conjugated, 344, 347, 368, 388, 391 Conjugation, 58, 344 Conjunctiva, 343, 344, 373 Connective Tissue, 325, 332, 342, 344, 349, 359, 361, 381, 384, 405, 411, 412, 418, 420 Connective Tissue Diseases, 325, 344 Consciousness, 322, 344, 348, 351, 356, 368, 406, 417 Constipation, 15, 303, 344, 398 Constriction, 208, 344, 376, 405, 427 Constriction, Pathologic, 344, 427 Consultation, 153, 344 Consumption, 27, 344, 349, 357, 391, 410 Contamination, 202, 344 Contractility, 37, 168, 169, 323, 344 Contraindications, ii, 283, 344 Contrast Media, 66, 223, 234, 344 Contrast medium, 130, 172, 323, 344, 345 Control group, 73, 344 Controlled clinical trial, 35, 57, 344, 408 Controlled study, 65, 344 Conus, 345, 406 Coordination, 204, 338, 339, 345, 387 Cor, 178, 203, 345 Cornea, 63, 324, 326, 345, 430 Coronary Angiography, 124, 345 Coronary Arteriosclerosis, 345, 387 Coronary Artery Bypass, 88, 120, 290, 345

437

Coronary Circulation, 323, 345 Coronary heart disease, 180, 181, 201, 286, 336, 345 Coronary Thrombosis, 345, 384, 387 Coronary Vasospasm, 173, 178, 197, 203, 345 Corpus, 345, 396, 403, 421, 429 Cortex, 182, 237, 345, 408 Cortical, 38, 40, 46, 171, 345, 413, 421 Corticosteroid, 345, 402, 417 Cortisol, 320, 346 Cortisone, 346, 402 Cranial, 338, 346, 366, 375, 392, 397 Craniocerebral Trauma, 329, 346, 366, 421 Creatine, 27, 346 Creatinine clearance, 21, 23, 27, 60, 179, 190, 346 Critical Care, 37, 96, 112, 116, 121, 123, 126, 221, 223, 238, 294, 346 Crossing-over, 346, 408 Crowding, 184, 346 Crystalluria, 117, 346 Culture Media, 75, 320, 346 Cultured cells, 69, 346 Curative, 346, 390, 411, 421 Cutaneous, 50, 118, 285, 335, 346, 378, 381, 413 Cyclic, 187, 199, 200, 318, 333, 335, 346, 365, 390, 399, 404, 421 Cyclophosphamide, 145, 346 Cyclosporine, 34, 151, 153, 179, 234, 235, 347 Cyst, 66, 255, 347 Cystathionine beta-Synthase, 347, 370 Cysteinyl, 347, 384 Cystitis, 90, 347 Cytochrome, 136, 142, 340, 347 Cytokine, 34, 37, 49, 51, 71, 75, 76, 80, 162, 347, 421 Cytomegalovirus, 74, 347 Cytoplasm, 326, 329, 337, 339, 347, 356, 365, 384, 411, 428 Cytoskeleton, 38, 41, 48, 347, 374 Cytotoxic, 37, 82, 347, 372, 407, 415 Cytotoxicity, 37, 321, 341, 347 D Dairy Products, 233, 347 Data Collection, 74, 77, 78, 347, 360 De novo, 81, 347 Deamination, 329, 348, 350, 426 Decarboxylation, 348, 369, 406 Decision Making, 20, 348

Defense Mechanisms, 348, 374 Degenerative, 174, 287, 323, 345, 348, 368, 381, 393, 411 Dehydration, 339, 348 Deletion, 30, 42, 45, 47, 195, 326, 348, 362 Delirium, 348, 366 Delivery of Health Care, 348, 366 Dementia, 162, 175, 200, 318, 348 Denaturation, 348, 368 Dendrites, 348, 390 Density, 91, 153, 201, 235, 331, 332, 338, 348, 352, 379, 392, 416 Dental Caries, 25, 348 Dental Plaque, 25, 348 Dentition, 25, 348 Depolarization, 349, 414 Dermal, 238, 349 Dermatitis, 162, 349 Dermatosis, 114, 349 Dermis, 349, 423 DES, 211, 322, 349 Deuterium, 349, 370 Developing Countries, 250, 349 Dextrorotatory, 173, 198, 349 Diabetes Insipidus, 349, 401 Diabetic Retinopathy, 172, 198, 246, 254, 349, 399 Diagnostic procedure, 159, 242, 252, 349 Dialysate, 65, 229, 240, 282, 349 Dialyzer, 279, 282, 349, 367 Diaphragm, 41, 349, 368 Diarrhea, 75, 349 Diastole, 349 Diastolic, 19, 173, 197, 349, 371 Diastolic blood pressure, 19, 349 Didanosine, 101, 349, 350 Dideoxyadenosine, 350 Diencephalon, 338, 350, 371, 421 Dietary Fats, 350, 379 Dietetics, 135, 243, 244, 350 Digestion, 121, 320, 330, 332, 350, 352, 361, 375, 379, 380, 395, 396, 417, 427 Digestive system, 157, 350, 386 Digestive tract, 183, 350, 415 Dihydropyridines, 172, 350 Dihydrotestosterone, 350, 408 Dilatation, 66, 317, 323, 350, 402, 427 Dilatation, Pathologic, 350, 427 Dilation, 200, 332, 350, 427 Diltiazem, 172, 350 Dilution, 217, 350, 357 Dipyridamole, 35, 350

438 Renal failure

Direct, iii, 30, 47, 64, 72, 77, 145, 181, 259, 341, 350, 351, 370, 381, 397, 401, 408, 418, 420 Discrete, 350, 380, 404, 430 Disease Progression, 56, 57, 350, 428 Disinfectant, 351, 357, 384 Disparity, 50, 351 Disposition, 83, 351 Dissection, 54, 351 Dissociation, 319, 351 Distal, 32, 42, 200, 345, 351, 353, 377, 405 Diuresis, 231, 333, 351, 421 Diuretics, Thiazide, 261, 325, 351 Dizziness, 173, 197, 351 DNA Topoisomerase, 351, 362 Dopamine, 89, 204, 251, 341, 351, 359, 390, 398 Dorsal, 351, 401, 416 Dosage Forms, 161, 163, 166, 351 Dose-dependent, 52, 352 Dosimetry, 219, 352 Double-blind, 35, 51, 153, 352 Double-blinded, 51, 153, 352 Drug Design, 78, 264, 352 Drug Interactions, 240, 264, 352 Drug Monitoring, 219, 256, 352 Drug Tolerance, 352, 423 Duct, 66, 322, 336, 342, 352, 358, 412, 417 Duodenitis, 19, 352 Duodenum, 19, 330, 352, 355, 361, 377, 395, 396, 418 Dysgerminoma, 105, 352 Dyslipidemia, 201, 352 Dysmenorrhea, 203, 352 Dysmenorrhoea, 200, 352 Dyspepsia, 98, 352 Dysplasia, 275, 352 Dyspnea, 101, 352, 406 Dystrophin, 353, 387 Dystrophy, 174, 274, 353 E Eating Disorders, 207, 210, 302, 353 Edema, 15, 20, 49, 165, 173, 178, 197, 200, 203, 206 Effector, 201, 317, 342, 353, 399 Efferent, 65, 353, 416 Efficacy, 23, 35, 40, 50, 56, 62, 73, 98, 125, 126, 185, 234, 352, 353, 372 Elasticity, 345, 353, 415 Elastin, 342, 344, 353, 358 Elective, 301, 353 Electrocardiogram, 148, 353

Electrocoagulation, 341, 353 Electrode, 189, 353 Electrophoresis, 70, 353, 368, 402 Electroporation, 47, 353 Emaciation, 318, 353 Embolectomy, 353, 422 Emboli, 242, 353, 354 Embolism, 296, 354, 406 Embolization, 242, 354 Embolus, 354, 373 Embryo, 317, 332, 337, 354, 362, 373, 393 Emollient, 354, 364, 392 Emphysema, 194, 340, 354 Emulsion, 328, 354 Enalapril, 23, 91, 98, 261, 354 Enamel, 25, 348, 354 Encephalopathy, 23, 184, 239, 354 Endarterectomy, 323, 354 Endemic, 339, 354, 382, 417 Endocrine Glands, 354, 395 Endocrine System, 217, 354 Endocytosis, 56, 354 Endopeptidases, 354, 404 Endorphins, 355, 390 Endoscope, 355 Endoscopic, 98, 242, 355 Endothelial cell, 37, 38, 39, 44, 46, 55, 62, 63, 76, 116, 195, 207, 331, 355, 422 Endothelium, 49, 55, 99, 180, 199, 200, 223, 323, 355, 390 Endothelium, Lymphatic, 355 Endothelium, Vascular, 355 Endothelium-derived, 199, 200, 355, 390 Endotoxic, 174, 355, 379 Endotoxin, 355, 425 End-stage renal, 17, 19, 33, 36, 43, 45, 48, 50, 57, 65, 70, 73, 74, 78, 81, 83, 85, 136, 152, 153, 170, 218, 234, 237, 240, 241, 242, 243, 245, 246, 254, 256 Energy balance, 64, 355, 378 Energy Intake, 18, 355 Enhancer, 47, 202, 355, 410 Enkephalins, 355, 390 Environmental Exposure, 42, 355, 392 Environmental Health, 270, 272, 355 Enzymatic, 211, 321, 334, 336, 343, 348, 350, 355, 369, 384, 410 Enzyme Inhibitors, 22, 355, 400 Eosinophils, 356, 365, 378 Epidemic, 25, 31, 356, 417 Epidemiological, 195, 216, 254, 356 Epidermal, 285, 356, 383

439

Epidermal Growth Factor, 285, 356 Epidermis, 349, 356, 406 Epigastric, 356, 394 Epilepticus, 251, 356 Epinephrine, 199, 319, 351, 356, 390, 425 Epiphyseal, 72, 356 Epithelial, 32, 34, 38, 41, 48, 49, 55, 63, 66, 68, 75, 76, 195, 196, 197, 339, 356, 368, 378 Epithelial Cells, 32, 48, 49, 63, 75, 76, 196, 197, 339, 356, 368, 378 Epithelium, 64, 75, 329, 340, 355, 356, 361, 376, 430 Equipment and Supplies, 17, 217, 280, 356 Erectile, 180, 185, 356, 396 Erection, 185, 200, 356 ERV, 272, 356, 358 Erythroblasts, 356, 357 Erythrocyte Indices, 331, 356 Erythrocyte Volume, 331, 357 Erythrocytes, 119, 170, 322, 323, 331, 332, 356, 357, 367, 408 Erythroid Progenitor Cells, 170, 356, 357 Erythropoiesis, 170, 356, 357 Erythropoietin, 47, 66, 135, 160, 170, 192, 193, 215, 217, 228, 233, 237, 251, 255, 285 Esophagitis, 19, 357, 419 Esophagus, 19, 350, 357, 366, 396, 398, 409, 418 Essential Tremor, 274, 357 Estradiol, 32, 196, 357 Estrogen, 181, 196, 357 Ethanol, 242, 357 Ether, 209, 326, 357 Ethnic Groups, 33, 216, 357 Eukaryotic Cells, 357, 373, 425 Evacuation, 344, 357, 361 Evoke, 357, 417 Excitation, 72, 322, 327, 357, 390 Excrete, 45, 318, 326, 357, 377, 410 Exercise Test, 357, 358 Exercise Tolerance, 236, 358 Exhaustion, 255, 324, 358, 382 Exocrine, 358, 394, 395 Exogenous, 37, 51, 68, 228, 335, 354, 358, 362, 364, 404, 425 Exon, 42, 358 Expiratory, 356, 358 Expiratory Reserve Volume, 356, 358 Extensor, 358, 405 External-beam radiation, 358, 376, 407, 429

Extracellular Matrix, 34, 48, 57, 66, 165, 199, 344, 358, 359, 360, 374 Extracellular Matrix Proteins, 57, 358, 360 Extracellular Space, 72, 165, 358, 385 Extracorporeal, 239, 358, 367 Extraction, 72, 358 Extrapyramidal, 351, 358 Extravascular, 84, 358 Extremity, 127, 150, 358 Exudate, 333, 358 F Family Planning, 271, 358 Fat, 40, 148, 191, 241, 244 Fat Body, 191, 359 Fatigue, 94, 102, 241, 255, 359, 366 Fatty acids, 201, 320, 359, 403, 421, 422 Febrile, 287, 359, 382 Feces, 344, 359, 418 Femoral, 336, 359 Femoral Artery, 336, 359 Fenoldopam, 37, 202, 203, 359 Ferritin, 250, 359 Fetus, 317, 332, 357, 359, 400, 402, 427 Fibrillation, 172, 198, 291, 359 Fibrin, 331, 359, 398, 422 Fibrinogen, 26, 74, 102, 108, 359, 400, 422 Fibroblasts, 359, 375 Fibronectins, 358, 359 Fibrosis, 56, 122, 145, 175, 181, 189, 200, 275, 321, 359, 406, 412, 413 Filtration, 12, 41, 56, 68, 72, 148, 190, 195, 230, 234, 235, 241, 243, 246, 359, 377 Fistula, 36, 149, 282, 359 Fluconazole, 97, 359 Fluid Therapy, 359, 391 Fluorescence, 32, 72, 177, 359 Fluorouracil, 350, 360 Flutter, 172, 198, 360 Focal Adhesions, 48, 360 Focus Groups, 216, 360 Folate, 103, 108, 150, 360 Fold, 42, 69, 360, 384, 392 Folic Acid, 108, 129, 137, 138, 360 Follicular Phase, 196, 360 Foramen, 339, 360, 398 Forearm, 112, 331, 360 Free Radicals, 63, 325, 351, 360, 388 Friction, 360, 380 Fungi, 325, 327, 344, 360, 365, 385, 429 Fungus, 335, 338, 360 Furosemide, 194, 360

440 Renal failure

G Gallbladder, 317, 330, 350, 361, 395 Gallstones, 110, 361 Gamma Rays, 361, 407 Ganglia, 317, 329, 361, 389, 397, 416, 419 Ganglion, 361, 392, 430 Ganglionic Blockers, 325, 361 Gas, 322, 356, 361, 370, 390, 410, 419, 427, 428 Gas exchange, 361, 410, 428 Gastric, 19, 104, 116, 135, 175, 237, 328, 335, 336, 340, 351, 356, 361, 366, 369, 396 Gastric Bypass, 116, 361 Gastric Emptying, 19, 237, 361 Gastric Juices, 361, 396 Gastric Mucosa, 135, 361 Gastrin, 340, 361, 369 Gastritis, 19, 361, 419 Gastrointestinal tract, 323, 326, 357, 361, 414, 425 Gastroparesis, 232, 234, 237, 361 Gelatin, 46, 346, 361, 364, 419, 421 Gene Deletion, 42, 362 Gene Duplication, 43, 362 Gene Expression, 33, 42, 46, 47, 53, 68, 80, 174, 275, 362 Gene Targeting, 60, 362 Gene Therapy, 38, 47, 52, 160, 362 Genetic Code, 362, 391 Genetic Engineering, 24, 330, 341, 362 Genetic Markers, 34, 362 Genetic Predisposition to Disease, 39, 362 Genetics, 59, 61, 344, 362, 386 Genistein, 51, 362 Genital, 185, 200, 341, 362, 426 Genotype, 194, 362, 398 Germ cell tumors, 352, 362 Germ Cells, 352, 362, 393, 420 Germ Layers, 332, 362 Germfree, 61, 362 Gestation, 40, 363, 400 Gestational, 42, 363 Giant Cells, 363, 412 Gingival Hyperplasia, 25, 363 Gingivitis, 348, 363 Gland, 30 Glomerular Filtration Rate, 72, 148, 230, 234, 235, 241, 246, 363, 377 Glomeruli, 34, 41, 57, 70, 363 Glomerulonephritis, 15, 42, 57, 104, 171, 172, 180, 197, 198, 295, 363, 381

Glomerulosclerosis, 33, 46, 122, 145, 181, 211, 363 Glomerulus, 54, 59, 68, 169, 363, 377, 389 Glucocorticoid, 184, 363, 402 Gluconeogenesis, 31, 363 Glucose Intolerance, 233, 239, 243, 349, 363 Glucose tolerance, 146, 363 Glucose Tolerance Test, 146, 363, 364 Glucuronic Acid, 165, 364, 368 Glucuronides, 364 Glutamic Acid, 360, 364, 390, 403 Glutathione Peroxidase, 364, 413 Glycerol, 201, 335, 364, 399 Glycine, 212, 321, 364, 390, 414 Glycogen, 31, 178, 203, 364 Glycoprotein, 357, 359, 363, 364, 365, 378, 386, 422, 425 Glycosaminoglycans, 358, 364, 405 Goats, 347, 364 Gonad, 352, 364 Gonadal, 105, 364, 417 Gonadal Dysgenesis, 105, 364 Gonadotropin, 340, 364 Gout, 43, 167, 342, 364 Governing Board, 364, 402 Gp120, 365, 397 Grade, 105, 352, 365 Graft, 17, 35, 62, 143, 149, 162, 179, 211, 254, 282, 290, 365, 369, 387, 388 Graft Rejection, 162, 179, 365 Graft Survival, 62, 365 Grafting, 120, 127, 345, 365, 372 Graft-versus-host disease, 365, 387 Gram-negative, 338, 355, 365, 372, 405, 428 Gram-Negative Bacteria, 355, 365 Gram-positive, 338, 365, 372, 418, 420 Gram-Positive Bacteria, 365, 420 Granulocytes, 365, 378, 387, 415, 429 Grasses, 360, 365 Growth factors, 12, 47, 82, 229, 235, 238, 284, 365 Growth Plate, 72, 365 Guanine, 106, 167, 365, 406 Guanylate Cyclase, 365, 390 H Haematuria, 88, 365 Haemodialysis, 98, 100, 143, 240, 365 Half-Life, 218, 234, 337, 366 Haplotypes, 195, 366 Haptens, 319, 366 Hay Fever, 320, 366

441

Headache, 173, 197, 333, 366, 373 Headache Disorders, 366 Health Behavior, 79, 366 Health Care Costs, 73, 366 Health Expenditures, 366 Health Services, iv, 25, 78, 272, 293, 303, 348, 366 Health Status, 28, 77, 366 Hearing aid, 14, 366 Heart attack, 69, 77, 336, 366 Heart failure, 135, 160, 161, 163, 164, 166, 168, 172, 175, 176, 178, 180, 184, 187, 194, 197, 198, 199, 200, 202, 203, 204, 208, 230, 290, 291, 294, 295, 296, 297 Heartburn, 366, 368 Heat Stroke, 129, 366 Hematocrit, 28, 47, 215, 255, 331, 356, 366 Hematopoiesis, 251, 367 Hematopoietic tissue, 170, 332, 367 Hematuria, 21, 59, 367 Heme, 46, 103, 330, 347, 367, 388, 394 Hemodiafiltration, 84, 367, 425 Hemodialyzer, 250, 367 Hemodynamics, 11, 20, 41, 193, 367 Hemofiltration, 16, 17, 83, 106, 107, 112, 116, 240, 241, 243, 250, 367, 425 Hemoglobin, 21, 176, 194, 215, 255, 323, 330, 331, 339, 356, 357, 367, 378, 421 Hemoglobin A, 339, 367 Hemoglobinopathies, 362, 367 Hemoglobinuria, 274, 367 Hemolysis, 116, 367 Hemolytic, 36, 39, 44, 49, 71, 75, 192, 367, 421 Hemoperfusion, 228, 367 Hemophilia, 193, 275, 368 Hemorrhage, 323, 346, 353, 366, 368, 388, 406, 418, 429 Hemostasis, 368, 374, 414 Heparin, 143, 297, 368 Hepatic, 23, 31, 178, 181, 184, 200, 201, 203, 206, 320, 342, 348, 363, 368, 380 Hepatic Encephalopathy, 23, 184, 368 Hepatitis, 14, 15, 98, 100, 105, 107, 110, 113, 121, 181, 192, 295, 368 Hepatocyte, 83, 171, 172, 368 Hepatocyte Growth Factor, 83, 171, 172, 368 Hepatorenal Syndrome, 217, 368 Hereditary, 66, 344, 364, 368, 389, 411, 421 Heredity, 361, 362, 368 Hernia, 19, 368

Herpes, 318, 368 Heterodimers, 368, 374, 424 Heteroduplex Analysis, 42, 368 Heterogeneity, 33, 319, 368 Hiatal Hernia, 19, 368 Hirudin, 143, 369 Histamine, 322, 340, 369 Histidine, 369, 399 Histology, 40, 73, 136, 205, 220, 369 Holidays, 218, 369 Homeostasis, 58, 59, 80, 190, 205, 209, 217, 227, 232, 234, 246, 369 Homodimer, 369, 424 Homologous, 320, 329, 331, 346, 362, 369, 413, 420 Hormonal, 32, 194, 198, 200, 223, 227, 232, 243, 328, 346, 369, 429 Hormonal therapy, 227, 369 Hormone therapy, 91, 105, 227, 369 Host, 34, 75, 162, 329, 365, 369, 372, 401, 427, 428 Human Genome Project, 54, 276, 369 Human growth hormone, 16, 64, 72, 98, 137, 146, 253, 369 Humoral, 365, 369 Hybrid, 47, 54, 329, 341, 369 Hybridization, 42, 55, 57, 68, 73, 369, 386 Hybridomas, 353, 369, 375 Hydatidiform Mole, 340, 369 Hydralazine, 184, 262, 263, 370 Hydrogen Peroxide, 47, 167, 364, 370, 379, 419 Hydrogenation, 330, 370 Hydrolysis, 201, 330, 337, 341, 370, 379, 399, 405 Hydronephrosis, 30, 90, 370 Hydrophobic, 194, 370, 379 Hydroureter, 30, 90, 370 Hydroxylation, 334, 370 Hydroxylysine, 342, 370 Hydroxyproline, 321, 342, 370 Hyperaldosteronism, 172, 370 Hyperbilirubinemia, 231, 370, 377 Hypercalcemia, 33, 136, 156, 253, 370 Hypercalciuria, 253, 370 Hypercholesterolemia, 235, 352, 370 Hyperglycemia, 31, 50, 68, 203, 233, 370 Hyperhomocysteinemia, 89, 108, 347, 370 Hyperkalaemia, 128, 370 Hyperlipidemia, 217, 297, 352, 370 Hyperoxaluria, 45, 370 Hyperphagia, 210, 370

442 Renal failure

Hyperplasia, 25, 29, 35, 61, 172, 198, 241, 370 Hypersensitivity, 334, 371, 411 Hypertension, Pulmonary, 180, 200, 371 Hypertension, Renal, 40, 172, 180, 198, 371 Hypertension, Renovascular, 180, 371 Hyperthyroidism, 371, 403 Hypertriglyceridemia, 109, 352, 371 Hypertrophic cardiomyopathy, 172, 198, 371 Hypertrophy, 40, 102, 173, 185, 197, 217, 345, 371, 424 Hyperuricemia, 44, 364, 371 Hypnotic, 329, 371, 421 Hypotension, 37, 177, 189, 361, 371 Hypothalamic, 65, 371 Hypothalamus, 65, 182, 210, 328, 332, 350, 371, 400, 421 Hypovolemia, 177, 371 Hypoxanthine, 83, 167, 371, 429 Hypoxia, 20, 29, 38, 47, 71, 170, 323, 348, 371, 421 Hypoxic, 29, 54, 174, 371 I Ibuprofen, 109, 371, 377 Idiopathic, 86, 232, 371, 412 Ileum, 337, 371, 377 Imidazole, 175, 176, 331, 369, 371 Imipenem, 84, 85, 340, 371 Immune function, 153, 162, 372, 424 Immune response, 61, 110, 153, 319, 325, 328, 346, 365, 366, 372, 382, 415, 419, 427, 428 Immune Sera, 372 Immune system, 147, 151, 153, 194, 328, 330, 372, 381, 387, 398, 427, 429 Immunity, 318, 372, 424 Immunization, 49, 61, 296, 302, 372 Immunodeficiency, 108, 200, 274, 318, 372 Immunogenic, 14, 61, 372, 379 Immunoglobulin, 49, 114, 298, 324, 372, 386 Immunohistochemistry, 60, 372 Immunologic, 110, 190, 238, 339, 372, 407 Immunology, 55, 319, 372 Immunophilin, 334, 372 Immunosuppressive, 128, 144, 153, 241, 334, 346, 363, 372, 420 Immunosuppressive Agents, 241, 372 Impairment, 71, 173, 184, 197, 198, 217, 233, 239, 243, 245, 327, 348, 372, 383, 395 Implant radiation, 372, 375, 376, 407, 429

Implantation, 81, 343, 372 Impotence, 175, 204, 356, 372 In situ, 42, 55, 57, 73, 163, 372 In Situ Hybridization, 42, 55, 73, 373 In vitro, 29, 40, 49, 53, 55, 61, 62, 66, 68, 69, 195, 362, 373, 412, 420, 422 Incision, 373, 376 Incontinence, 200, 373 Incubated, 39, 373 Indicative, 69, 221, 373, 396, 427 Indomethacin, 22, 211, 373 Induction, 36, 46, 49, 50, 52, 57, 61, 63, 69, 81, 136, 178, 193, 203, 322, 361, 373, 407 Infancy, 253, 373, 411 Infarction, 68, 150, 172, 173, 175, 180, 186, 187, 196, 197, 198, 230, 286, 288, 299, 303 Infection Control, 281, 373 Infertility, 373, 426 Infiltration, 12, 20, 56, 252, 363, 373, 430 Inflammatory bowel disease, 23, 373 Influenza, 304, 373 Infusion, 64, 97, 171, 208, 210, 374, 388, 424 Ingestion, 31, 49, 154, 169, 317, 333, 364, 370, 374, 400, 421 Inhalation, 100, 374, 400 Initiation, 12, 21, 24, 38, 52, 57, 78, 185, 189, 216, 237, 238, 293, 374, 380, 403, 423 Inner ear, 337, 374, 427 Inorganic, 183, 341, 374, 399, 402 Inotropic, 37, 168, 351, 374 Insecticides, 374, 429 Insight, 54, 69, 235, 374 Insulator, 374, 387 Insulin, 16, 23, 40, 50, 70, 81, 112, 194, 233, 246, 254, 363, 374, 376, 394, 425 Insulin-dependent diabetes mellitus, 23, 254, 374 Insulin-like, 16, 374 Integrins, 48, 53, 77, 84, 360, 374 Intensive Care, 95, 112, 122, 124, 125, 127, 136, 182, 183, 221, 374 Interferon, 192, 374 Interferon-alpha, 374 Interleukin-1, 34, 145, 162, 375 Interleukin-10, 34, 145, 375 Interleukin-2, 375 Interleukin-6, 34, 73, 127, 375 Interleukins, 372, 375 Intermittent, 72, 91, 106, 112, 220, 359, 375, 380, 398 Internal Medicine, 36, 54, 55, 56, 63, 68, 75, 76, 87, 102, 125, 135, 375, 389

443

Internal radiation, 375, 376, 407, 429 Interpersonal Relations, 77, 375 Interstitial, 34, 44, 46, 56, 171, 181, 332, 358, 375, 376, 389, 409, 429 Intervention Studies, 49, 375 Intervertebral, 375, 380, 413 Intervertebral Disk Displacement, 375, 380, 413 Intestinal, 49, 83, 121, 155, 156, 175, 183, 238, 334, 336, 339, 363, 375, 382, 427, 428 Intestinal Mucosa, 375, 427 Intestine, 332, 342, 375, 378, 384, 397 Intoxication, 348, 375, 427, 429 Intracranial Hypertension, 89, 366, 375 Intraindividual, 255, 375 Intramuscular, 47, 110, 375, 395 Intraperitoneal, 230, 375 Intravascular, 86, 100, 171, 227, 376 Intravenous, 19, 38, 83, 84, 98, 151, 298, 374, 376, 395 Intrinsic, 62, 115, 319, 329, 376 Intubation, 336, 376 Inulin, 363, 376 Invasive, 29, 59, 125, 165, 242, 369, 372, 376, 382 Involuntary, 329, 357, 359, 376, 388, 414, 415 Iodine, 137, 376 Ion Channels, 66, 184, 201, 376, 398 Ionizing, 321, 355, 376, 407 Ions, 184, 317, 329, 334, 335, 339, 351, 353, 370, 376, 386 Irinotecan, 130, 376 Iris, 324, 327, 345, 376, 406 Irradiation, 193, 376, 429 Islet, 50, 148, 376 Isoenzymes, 180, 376 Isoflavones, 51, 152, 153, 376 Isopropyl, 212, 377 Isozymes, 39, 69, 377 J Jaundice, 230, 231, 368, 370, 377 Jejunum, 361, 377 Joint, 26, 66, 80, 241, 288, 327, 377, 393, 417, 420 K Kanamycin, 321, 377 Kb, 195, 270, 377, 378 Keratolytic, 348, 377 Keto, 81, 134, 377 Ketoprofen, 82, 377 Kidney Cortex, 377, 384

Kidney Failure, Acute, 284, 377 Kidney Failure, Chronic, 143, 144, 146, 147, 149, 150, 152, 154, 155, 156, 284, 377 Kidney Pelvis, 377, 426 Kidney stone, 167, 234, 370, 377, 389, 394, 410, 426 Kilobase, 42, 378 Kinetic, 59, 83, 241, 376, 378 L Labile, 342, 378 Laminin, 46, 329, 358, 378 Lamivudine, 100, 128, 378 Large Intestine, 337, 342, 350, 375, 378, 408, 415 Latent, 289, 362, 378, 401, 402 Least-Squares Analysis, 378, 409 Legionellosis, 87, 378 Leishmaniasis, 378, 396 Length of Stay, 20, 149, 285, 378 Leptin, 96, 112, 378 Lethal, 52, 61, 193, 329, 378 Leucine, 55, 378, 396 Leucocyte, 378 Leukaemia, 90, 378 Leukapheresis, 151, 153, 378 Leukemia, 97, 155, 274, 362, 378 Leukocyte Count, 21, 378 Leukocytes, 55, 71, 77, 180, 329, 331, 332, 339, 356, 365, 373, 374, 375, 378, 425 Library Services, 312, 379 Life Expectancy, 18, 379 Ligament, 379, 404, 417 Ligands, 77, 201, 207, 337, 374, 379 Ligation, 68, 172, 379 Likelihood Functions, 379, 409 Linear Models, 379, 409 Linkage, 22, 33, 40, 42, 43, 44, 195, 337, 362, 379 Linkage Disequilibrium, 40, 195, 379 Lipase, 40, 201, 379 Lipid, 19, 30, 47, 54, 85, 181, 191, 235, 240 Lipid A, 30, 47, 235, 379 Lipid Peroxidation, 379, 394 Lipolysis, 201, 379 Lipopolysaccharide, 75, 365, 379 Lipoprotein, 40, 108, 201, 235, 352, 365, 379, 380 Lipoprotein Lipase, 40, 379 Lipoprotein(a), 108, 379 Liver Cirrhosis, 165, 178, 203, 368, 380 Liver scan, 380, 412 Liver Transplantation, 45, 89, 380

444 Renal failure

Loading dose, 241, 380 Lobe, 369, 380, 395 Localization, 41, 43, 48, 53, 60, 70, 219, 372, 380 Localized, 200, 322, 348, 353, 373, 378, 380, 400, 413, 425 Logistic Models, 380, 409 Longitudinal study, 26, 60, 77, 380 Long-Term Care, 301, 380 Loop, 115, 261, 361, 368, 380 Low Back Pain, 288, 380 Low-density lipoprotein, 116, 235, 352, 379, 380 Lubricants, 380, 381 Lubrication, 200, 380 Lucida, 378, 381 Luciferase, 68, 381 Lumbar, 116, 328, 336, 375, 380, 381 Lumen, 113, 355, 381 Lupus, 42, 162, 287, 324, 325, 381, 420 Lupus Nephritis, 42, 381 Lymph, 252, 328, 340, 352, 355, 381, 395, 412, 418 Lymph node, 252, 328, 352, 381, 395, 412 Lymphatic, 355, 373, 381, 384, 416, 417, 422 Lymphatic system, 381, 416, 417, 422 Lymphocyte, 97, 318, 325, 381, 382, 383, 426 Lymphocyte Count, 318, 381 Lymphocytic, 90, 381 Lymphoid, 152, 324, 378, 381 Lymphoma, 21, 100, 126, 274, 381 Lytic, 287, 381 M Macrophage, 105, 191, 375, 381 Macula, 381 Macula Lutea, 381 Macular Degeneration, 174, 381 Maculopapular, 381, 413 Magnetic Resonance Imaging, 219, 382, 412 Major Histocompatibility Complex, 366, 382 Malabsorption, 274, 382 Malaria, 16, 88, 120, 162, 382 Malaria, Falciparum, 382 Malaria, Vivax, 382 Malformation, 14, 382 Malignancy, 33, 352, 382 Malignant, 21, 87, 116, 274, 318, 325, 340, 352, 362, 382, 386, 388, 407, 412, 420

Malignant tumor, 340, 382, 386 Malnutrition, 15, 65, 73, 78, 229, 230, 231, 237, 243, 244, 253, 256 Mammary, 165, 345, 379, 382 Mammogram, 334, 382, 385 Manic, 331, 382 Manifest, 237, 382 Maximum Tolerated Dose, 145, 352, 382 Meat, 49, 169, 233, 350, 382 Mediate, 34, 38, 47, 63, 68, 76, 77, 180, 201, 207, 337, 351, 382 Mediator, 51, 69, 198, 212, 375, 383, 414 Medical Records, 77, 383 Medical Staff, 352, 383 MEDLINE, 271, 273, 275, 383 Medullary, 29, 38, 46, 55, 383 Megakaryocytes, 332, 383 Megaloblastic, 360, 383 Melanin, 376, 383, 398, 425 Melanocytes, 383 Melanoma, 274, 383, 425 Melphalan, 136, 383 Membrane Glycoproteins, 383 Memory, 175, 180, 203, 324, 348, 383 Menarche, 196, 383 Meninges, 337, 338, 346, 383, 416, 418 Meningitis, 359, 383 Menopause, 196, 287, 299, 383, 401, 402, 403 Menstrual Cycle, 360, 383, 403 Menstruation, 321, 352, 360, 383 Mental, iv, 25, 77, 157, 255, 270, 272, 276 Mental Disorders, 157, 383, 406 Mental Health, iv, 25, 77, 157, 270, 272, 384, 406 Mentors, 34, 384 Mercuric Chloride, 52, 142, 384 Mercury, 42, 384 Mesenchymal, 356, 369, 384 Mesenteric, 207, 384 Mesentery, 384, 398 Meta-Analysis, 15, 106, 384 Metabolic Clearance Rate, 233, 384 Metabolic disorder, 32, 349, 364, 384 Metabolite, 63, 107, 190, 333, 350, 384, 402 Metallothionein, 52, 384 Metastasis, 337, 384 Metastatic, 102, 130, 227, 384 Methionine, 89, 384, 419 Methylmalonic Acid, 113, 384 MI, 85, 88, 128, 135, 160, 195, 283, 315, 384 Microbe, 385, 423

445

Microbiological, 94, 385 Microbiology, 55, 94, 318, 329, 385 Microcalcifications, 334, 385 Microcirculation, 62, 380, 385 Microdialysis, 65, 385 Microfilaments, 360, 385 Microorganism, 342, 385, 396, 429 Micro-organism, 348, 362, 385, 399 Microscopy, 41, 45, 49, 135, 329, 368, 385 Migration, 46, 76, 77, 165, 193, 199, 385 Milliliter, 196, 332, 385 Mineralization, 183, 385, 393 Mineralocorticoids, 319, 346, 385 Mitosis, 326, 385 Mitral Valve, 117, 385 Mobility, 47, 68, 385 Modeling, 84, 241, 352, 385 Modification, 321, 350, 362, 385, 407, 430 Molecular Probes, 353, 386 Molecular Structure, 386, 424 Molecule, 16, 55, 75, 173, 174, 198, 235 Monitor, 34, 79, 96, 109, 153, 216, 220, 230, 346, 386, 391 Monoclonal, 369, 376, 386, 407, 412, 429 Monocyte, 111, 116, 386 Monocytes, 46, 76, 375, 379, 387, 421 Monogenic, 45, 386 Mononuclear, 386, 425 Monophosphate, 199, 200, 350, 386 Morphogenesis, 64, 76, 386 Morphology, 19, 54, 63, 75, 76, 221, 326, 386 Motility, 19, 121, 200, 373, 386, 414 Motion Sickness, 386, 388 Moxalactam, 84, 386 Mucins, 348, 386, 412 Mucolytic, 317, 386 Mucopurulent, 333, 386 Mucosa, 361, 381, 386, 418, 419 Mucositis, 386, 422 Multidose, 126, 386 Multiple Myeloma, 118, 136, 143, 144, 386 Multiple Organ Failure, 183, 386 Multiple sclerosis, 162, 387 Multivariate Analysis, 104, 387 Muscle Fibers, 327, 387, 388, 424 Muscle Proteins, 58, 387 Muscle relaxant, 387, 398 Muscle Relaxation, 185, 206, 387, 389 Muscle Spindles, 387, 399 Muscular Atrophy, 274, 387 Muscular Diseases, 387, 395

Muscular Dystrophies, 353, 387 Myalgia, 374, 387 Mycophenolate mofetil, 153, 387 Mydriatic, 350, 387 Myelin, 387 Myeloid Cells, 52, 387 Myeloma, 128, 136, 143, 144, 300, 387 Myocardial Ischemia, 164, 165, 323, 387 Myocardial Reperfusion, 388, 410 Myocardial Reperfusion Injury, 388, 410 Myocardium, 69, 323, 384, 387, 388 Myoglobin, 172, 388 Myopathy, 198, 236, 388 Myosin, 334, 388, 424 Myotonic Dystrophy, 274, 388 N Narcotic, 388, 394 Nasal Mucosa, 373, 388 Natriuresis, 199, 323, 388 Nausea, 232, 256, 325, 351, 361, 388, 405, 426 NCI, 9, 152, 155, 156, 269, 341, 388 Need, 11, 15, 19, 20, 26, 57, 63, 67, 85, 89, 130, 144, 161, 162, 165, 169, 171, 172, 176, 189, 198, 211, 215, 227, 230, 234, 245, 252, 253, 254, 256, 264, 279, 285, 307, 319, 340, 364, 388, 423 Needs Assessment, 79, 388 Neoplasia, 274, 388 Neoplasm, 155, 352, 388, 412 Neoplastic, 369, 381, 388 Nephritis, 42, 171, 205, 389 Nephrogenic, 51, 118, 389 Nephrolithiasis, 167, 234, 274, 318, 389 Nephrologist, 78, 231, 389 Nephron, 40, 66, 90, 92, 93, 94, 95, 111, 114, 129, 130, 172, 193, 363, 389 Nephrosis, 368, 389 Nephrotic, 15, 100, 114, 117, 128, 145, 168, 200, 203, 232, 235, 240, 241, 389 Nephrotic Syndrome, 15, 114, 117, 128, 145, 168, 203, 232, 235, 241, 389 Nephrotoxic, 35, 49, 53, 59, 172, 190, 205, 220, 231, 389 Nervous System, 36, 39, 65, 152, 162, 178, 185, 199, 203, 241, 274 Networks, 121, 389 Neural, 121, 174, 185, 319, 361, 369, 389 Neurodegenerative Diseases, 174, 175, 329, 389 Neurogenic, 65, 389 Neurologic, 228, 238, 389

446 Renal failure

Neuromuscular, 294, 317, 389, 395, 426 Neuromuscular Blockade, 294, 389 Neuromuscular Junction, 317, 389 Neuronal, 30, 174, 175, 334, 389 Neurons, 204, 341, 348, 361, 387, 389, 390, 416, 419, 420 Neuropathy, 175, 184, 246, 390, 413, 430 Neuropeptide, 203, 207, 210, 390 Neurosecretory Systems, 354, 390 Neurotransmitter, 203, 204, 317, 318, 321, 332, 351, 364, 369, 376, 390, 414, 419, 427 Neutralization, 187, 390 Neutrons, 321, 376, 390, 407 Neutrophil, 52, 109, 250, 390 Niacin, 138, 240, 390, 425 Nifedipine, 98, 390 Nitric Oxide, 47, 61, 63, 65, 98, 110, 136, 180, 199, 200, 390 Nonmalignant, 93, 390 Norepinephrine, 199, 319, 351, 390 Normotensive, 22, 390 Nuclear, 51, 59, 68, 100, 117, 174, 219, 303, 329, 335, 344, 357, 361, 391, 407, 426 Nuclear Medicine, 59, 100, 117, 303, 391 Nuclear Proteins, 174, 391 Nuclei, 174, 321, 344, 362, 382, 385, 390, 391, 392, 405 Nucleic acid, 160, 167, 184, 193, 329, 350, 362, 369, 371, 373, 390, 391, 406, 407, 411, 430 Nucleic Acid Hybridization, 369, 391 Nucleoproteins, 391 Nursing Care, 391, 396 Nutrition Assessment, 241, 391 Nutritional Status, 15, 24, 64, 73, 74, 135, 169, 229, 230, 234, 237, 238, 243, 256, 282, 291 Nutritional Support, 24, 243, 391 O Observational study, 107, 391 Obsessive-Compulsive Disorder, 203, 391 Occult, 15, 391 Odds Ratio, 391, 409 Odour, 326, 392, 426 Office Visits, 13, 392 Ointments, 351, 392 Oliguria, 20, 377, 392 Omentum, 81, 392 Oncogene, 274, 368, 392 Oncogenic, 374, 392, 401 Opacity, 348, 392 Opportunistic Infections, 153, 318, 392

Opsin, 392, 411 Optic Chiasm, 371, 392 Optic Disk, 345, 349, 381, 392 Optic Nerve, 392, 405, 410 Oral Health, 24, 25, 392 Organ Culture, 60, 392, 422 Organ Preservation, 63, 392 Orgasm, 200, 392 Ornithine, 392, 406 Osmolality, 66, 178, 393 Osmolarity, 184, 393 Osmoles, 393 Osmotic, 320, 393, 414 Osseointegration, 332, 393 Osteoarthritis, 162, 174, 304, 377, 393 Osteoclasts, 334, 393 Osteodystrophy, 13, 19, 23, 51, 217, 220, 229, 232, 241, 242, 281, 393 Osteogenesis, 332, 393 Osteomalacia, 242, 318, 333, 393 Osteoporosis, 33, 174, 180, 299, 301, 393 Ototoxic, 321, 393 Outpatient, 79, 393 Ovaries, 196, 393, 414, 420 Ovary, 357, 364, 393, 418 Overdose, 228, 393 Overweight, 40, 138, 393 Ovulation, 196, 360, 393 Ovum, 363, 393, 403, 429, 430 Oxalate, 45, 370, 394 Oxalic Acid, 334, 394 Oxidants, 53, 65, 394 Oxidation, 180, 209, 235, 317, 325, 347, 364, 379, 394, 421 Oxidation-Reduction, 394 Oxidative Stress, 51, 99, 154, 223, 394 Oxycodone, 137, 394 Oxygenase, 46, 103, 394 Oxygenation, 29, 394 Oxygenator, 336, 394 P Paediatric, 289, 394 Palliative, 394, 421 Pancreas Transplant, 18, 50, 115, 250, 394 Pancreas Transplantation, 18, 50, 115, 394 Pancreatectomy, 50, 395 Pancreatic, 19, 50, 122, 232, 240, 274, 336, 395 Pancreatic cancer, 274, 395 Pancreatic Insufficiency, 122, 395 Pancreatitis, 19, 103, 395 Papovaviridae, 395, 401

447

Paralyses, 182, 395 Paralysis, 182, 395 Paraplegia, 225, 395 Parathyroid, 14, 29, 32, 72, 94, 122, 154, 232, 237, 241, 242, 283, 334, 395, 411, 421 Parathyroid Glands, 241, 283, 395, 411 Parathyroid hormone, 14, 29, 32, 72, 122, 154, 232, 237, 241, 242, 334, 395 Parathyroidectomy, 19, 232, 241, 395 Parenteral, 23, 203, 243, 292, 355, 395 Parenteral Nutrition, 23, 243, 292, 395 Parietal, 395, 398 Parotid, 395, 412 Paroxysmal, 274, 323, 366, 395 Patch, 32, 345, 395, 424 Pathogen, 49, 61, 75, 396 Pathologic, 34, 49, 61, 71, 190, 227 Pathologic fracture, 227, 396 Pathologic Processes, 326, 396 Pathologist, 55, 396 Pathophysiology, 20, 28, 43, 55, 67, 68, 196, 199, 216, 217, 220, 221, 222, 226, 227, 228, 232, 396 Patient Care Management, 235, 238, 396 Patient Education, 79, 280, 283, 310, 312, 315, 396 Pediatrics, 21, 27, 44, 65, 67, 71, 72, 137, 287, 296, 302, 304 Pelvic, 396, 404 Pelvis, 317, 381, 393, 396, 427 Penicillin, 322, 324, 335, 396 Penicillinase, 335, 396 Penis, 185, 200, 396 Pentamidine, 82, 396 Pepsin, 340, 396 Pepsin A, 340, 396 Peptic, 19, 232, 396, 419 Peptic Ulcer, 19, 232, 396 Peptide, 70, 72, 168, 175, 178, 186, 193, 195, 197, 199, 203, 206, 210, 212 Peptide Elongation Factors, 396, 414 Peptide T, 210, 396 Perception, 15, 144, 397, 412 Percutaneous, 105, 114, 207, 242, 290, 291, 397 Perfusion, 20, 37, 38, 52, 94, 128, 142, 185, 209, 236, 289, 371, 397, 422 Pericardium, 397, 420 Periodontal disease, 25, 397 Perioperative, 231, 290, 301, 397 Perioperative Care, 231, 397 Peripheral blood, 51, 374, 397

Peripheral Nervous System, 210, 355, 389, 390, 395, 397, 419, 427 Peripheral Nervous System Diseases, 395, 397 Peripheral Vascular Disease, 150, 194, 198, 200, 201, 397 Peripheral vision, 397, 428 Peristalsis, 30, 397 Peritoneal Cavity, 237, 375, 397, 398 Peritoneum, 281, 282, 384, 392, 397, 398 Peritonitis, 19, 398 Peroxide, 167, 398 PH, 65, 90, 332, 398 Phagocyte, 52, 394, 398 Phagocytosis, 55, 77, 398 Pharmaceutical Preparations, 207, 338, 357, 361, 398 Pharmaceutical Solutions, 351, 398 Pharmacist, 251, 398 Pharmacodynamics, 154, 234, 241, 398 Pharmacokinetic, 84, 398 Pharmacologic, 17, 32, 38, 56, 58, 121, 321, 323, 328, 366, 398, 422, 423 Pharynx, 373, 398 Phenotype, 21, 33, 40, 42, 45, 59, 75, 362, 398 Phenyl, 164, 188, 208, 212, 398 Phenylalanine, 396, 398, 425 Phenytoin, 256, 398 Phorbol, 399, 404 Phorbol Esters, 399, 404 Phosphates, 134, 399 Phosphodiesterase, 184, 199, 200, 399 Phosphodiesterase Inhibitors, 199, 200, 399 Phosphoglycerate Kinase, 101, 399 Phospholipases, 32, 399, 414 Phospholipids, 324, 325, 335, 359, 379, 399, 404 Phosphoribosyl Pyrophosphate, 167, 399 Phosphorus, 23, 144, 154, 169, 183, 232, 237, 241, 242, 244, 256, 283, 334, 395, 399 Phosphorylates, 399, 404 Phosphorylation, 64, 76, 181, 399, 405 Photocoagulation, 341, 399 Physical Examination, 66, 146, 149, 151, 153, 230, 399 Physiologic, 19, 35, 77, 195, 209, 232, 236 Physiology, 29, 55, 58, 59, 61, 73, 172, 185, 196, 222, 236, 237, 244, 246, 281 Pigments, 330, 336, 399, 411 Pilot study, 144, 399

448 Renal failure

Pineal gland, 340, 399 Piperacillin, 84, 85, 399 Pituitary Gland, 178, 199, 203, 346, 400 Placenta, 357, 400, 403 Plants, 320, 332, 339, 341, 363, 376, 386, 390, 394, 399, 400, 405, 412, 423 Plaque, 25, 323, 400 Plasma cells, 324, 386, 387, 400 Plasma protein, 218, 320, 355, 400, 414 Plasmid, 47, 61, 400, 427 Platelet Activation, 71, 400, 415 Platelet Aggregation, 178, 203, 209, 322, 390, 400, 404, 422 Platelets, 76, 180, 194, 390, 400, 422 Platinum, 341, 380, 400 Pneumonia, 181, 333, 344, 396, 400 Point Mutation, 59, 400 Poisoning, 236, 333, 339, 348, 375, 384, 388, 400, 413 Polyarteritis Nodosa, 86, 400 Polycystic, 55, 60, 66, 255, 275, 401 Polydipsia, 246, 401 Polyhydramnios, 22, 401 Polymerase, 63, 174, 401, 403 Polymorphism, 195, 401 Polyomavirus, 90, 395, 401 Polyphagia, 246, 401 Polyposis, 342, 401 Polysaccharide, 165, 320, 325, 338, 401, 405 Polytetrafluoroethylene, 35, 254, 401 Polyuria, 66, 217, 246, 401 Pons, 332, 401 Posterior, 65, 178, 203, 322, 327, 328, 338, 340, 351, 376, 394, 401, 413 Postmenopausal, 180, 287, 299, 393, 401 Postnatal, 30, 40, 103, 401, 417 Postoperative, 151, 230, 231, 386, 401 Postoperative Complications, 231, 401 Postoperative Period, 151, 401 Postsynaptic, 401, 414 Potassium, 22, 139, 140, 168, 217, 220, 228, 237, 241, 243, 244, 256, 261 Potassium Compounds, 402 Potassium, Dietary, 217, 402 Potentiates, 375, 402 Potentiating, 170, 402 Potentiation, 402, 415 Practice Guidelines, 119, 215, 272, 286, 288, 290, 291, 293, 294, 298, 300, 301, 402 Practice Management, 227, 402 Prealbumin, 256, 402 Preclinical, 50, 62, 402

Precursor, 21, 46, 63, 198, 206 Predisposition, 39, 42, 402 Prednisolone, 402 Prednisone, 153, 253, 402 Premenopausal, 196, 402 Prenatal, 22, 30, 354, 402 Presynaptic, 390, 402 Prevalence, 12, 33, 36, 43, 74, 78, 79, 98, 121, 229, 230, 231, 239, 392, 402 Probe, 385, 402 Prodrug, 204, 402 Progeny, 344, 402 Progesterone, 403, 417 Prognostic factor, 403, 419 Progressive, 21, 24, 26, 33, 41, 42, 57, 60, 62, 66, 73, 82, 148, 154, 190, 204, 205, 209, 212, 218, 225, 228, 231, 239, 242, 252, 254, 274, 281 Projection, 348, 390, 392, 403, 408 Prokinetic Drugs, 232, 403 Proline, 342, 370, 403 Promoter, 33, 34, 41, 45, 47, 68, 81, 403 Promotor, 403, 410 Prone, 33, 403 Prophylaxis, 134, 211, 292, 303, 403, 411, 427 Proportional, 72, 393, 403 Propranolol, 173, 198, 403 Prospective Studies, 74, 403 Prospective study, 26, 28, 74, 115, 151, 380, 403 Prostaglandin, 113, 179, 184, 209, 323, 403, 404, 422 Prostaglandin Endoperoxides, 404, 422 Prostaglandins A, 179, 373, 403, 404 Prostaglandins D, 404 Prostaglandins H, 179, 404 Prostate, 102, 165, 227, 274, 330, 404, 425 Protease, 70, 342, 404 Protease Inhibitors, 70, 404 Protein Binding, 47, 84, 218, 234, 240, 404, 423 Protein C, 40, 54, 73, 180, 201, 235, 250 Protein Folding, 58, 404 Protein Kinase C, 64, 404 Protein Kinases, 32, 48, 63, 404 Protein S, 31, 36, 40, 44, 104, 275, 331, 362, 369, 396, 404, 411, 414, 421 Protein-Energy Malnutrition, 229, 405 Proteins, 16, 32, 41, 46, 47, 53, 55, 56, 57, 68, 70, 76, 81, 149, 161, 162, 169, 177, 181, 196, 197, 201, 230, 240, 241

449

Protein-Tyrosine Kinase, 362, 405 Proteinuria, 15, 22, 41, 56, 57, 68, 145, 172, 198, 205, 363, 386, 389, 405 Proteoglycan, 46, 405 Proteolytic, 212, 235, 343, 359, 405 Proteome, 70, 405 Protocol, 293, 297, 405 Protons, 321, 370, 376, 405, 407 Protozoa, 344, 378, 385, 405, 425 Protozoan, 338, 382, 405 Proximal, 32, 47, 53, 55, 56, 63, 69, 71, 75, 200, 241, 351, 361, 377, 402, 405 Pruritus, 241, 281, 405, 426 Pseudomonas, 400, 405 Pseudomonas Infections, 400, 405 Pseudotumor Cerebri, 375, 405 Psoriasis, 87, 162, 405, 411 Psychiatry, 219, 406, 428 Psychic, 383, 406, 413 Psychoactive, 406, 429 Psychological Theory, 27, 406 Puberty, 22, 25, 406 Public Health, 64, 66, 201, 247, 272, 300, 406 Public Policy, 271, 406 Pulmonary, 86, 122, 125, 168, 172, 180, 181, 194, 198, 200, 206, 207, 211, 228, 296, 303, 331, 344, 345, 357, 367, 371, 377, 406, 410, 428 Pulmonary Artery, 122, 331, 406, 428 Pulmonary Circulation, 371, 406 Pulmonary Edema, 168, 206, 228, 377, 406 Pulmonary Embolism, 296, 406 Pulmonary Fibrosis, 181, 406 Pulmonary hypertension, 122, 168, 172, 180, 198, 200, 207, 345, 406 Pulsation, 360, 406 Pulse, 87, 189, 386, 406 Pupil, 345, 350, 387, 406 Purines, 167, 329, 406, 414, 429 Purpura, 39, 406 Pustular, 87, 406 Putrefaction, 406 Putrescine, 69, 111, 406 Pyrimidines, 329, 406, 414 Q Quality of Life, 26, 28, 73, 81, 169, 209, 225, 230, 233, 236, 255, 282, 407, 419 Quaternary, 175, 176, 404, 407 R Race, 173, 197, 383, 385, 407 Racemic, 173, 197, 383, 407

Radiation, 41, 227, 323, 328, 355, 358, 359, 360, 361, 375, 376, 407, 412, 425, 429 Radiation therapy, 227, 358, 375, 376, 407, 429 Radioactivity, 72, 407 Radiography, 323, 344, 345, 407, 426 Radioimmunotherapy, 407 Radioisotope, 357, 407, 423 Radiolabeled, 72, 376, 407, 429 Radiological, 397, 407 Radiology, 59, 103, 113, 291, 391, 407 Radiotherapy, 170, 332, 376, 407, 429 Randomized, 16, 35, 36, 51, 57, 65, 66, 79, 98, 106, 146, 147, 153, 353, 407, 408 Randomized clinical trial, 66, 407 Randomized Controlled Trials, 106, 408 Reactivation, 82, 408 Reactive Oxygen Species, 52, 65, 408 Reagent, 191, 381, 394, 408 Receptors, Transforming Growth Factor beta, 57, 408 Recombinant, 16, 64, 66, 72, 137, 146, 161, 162, 165, 167, 192, 193, 197, 217, 233, 253 Recombination, 30, 329, 344, 362, 408 Reconstitution, 75, 88, 408 Rectum, 206, 326, 332, 342, 350, 361, 373, 378, 404, 408, 419 Recurrence, 34, 253, 331, 340, 408 Red blood cells, 194, 220, 233, 255, 357, 367, 394, 408, 412 Red Nucleus, 327, 408 Reductase, 45, 408 Refer, 9, 29, 170, 333, 342, 351, 355, 360, 368, 380, 381, 390, 407, 408, 423 Reflux, 104, 126, 409, 419 Refraction, 409, 416 Refractory, 37, 227, 353, 409 Regeneration, 53, 54, 64, 69, 81, 83, 92, 408, 409 Regimen, 14, 26, 79, 101, 153, 182, 192, 217, 230, 353, 409 Regression Analysis, 14, 409 Rehabilitative, 230, 236, 409 Rehydration, 231, 409 Relapse, 97, 409 Relative risk, 20, 409 Reliability, 256, 409 Remission, 331, 408, 409 Renal Artery, 68, 172, 242, 371, 409 Renal cell carcinoma, 75, 409 Renal Circulation, 177, 409 Renal Dialysis, 26, 169, 409

450 Renal failure

Renal Osteodystrophy, 13, 19, 51, 109, 128, 220, 229, 232, 241, 281, 409 Renal pelvis, 377, 409 Renal tubular, 32, 48, 55, 63, 75, 76, 193, 217, 236, 246, 410, 426 Renal tubular acidosis, 217, 246, 410 Renin, 23, 40, 65, 71, 195, 198, 212, 237, 323, 335, 410 Renin-Angiotensin System, 40, 65, 71, 195, 323, 335, 410 Renovascular, 59, 65, 80, 179, 180, 410 Reperfusion, 38, 46, 52, 62, 63, 68, 75, 174, 388, 410 Reperfusion Injury, 38, 52, 62, 63, 68, 174, 410 Resorption, 334, 393, 410 Respiration, 386, 410 Respiratory Physiology, 410, 428 Respiratory System, 410, 427 Response Elements, 81, 410 Restoration, 388, 408, 409, 410, 429 Retina, 175, 340, 343, 345, 349, 381, 392, 410, 411, 412, 429 Retinal, 174, 349, 351, 392, 410, 411 Retinoblastoma, 274, 411 Retinoids, 411, 428 Retinol, 410, 411 Retinopathy, 103, 172, 180, 198, 246, 254, 349, 411 Retrospective, 20, 22, 27, 411 Retroviral vector, 362, 411 Rhabdomyolysis, 46, 86, 87, 101, 116, 124, 126, 136, 171, 411 Rheumatism, 371, 411 Rheumatoid, 162, 165, 293, 299, 377, 394, 411 Rheumatoid arthritis, 162, 165, 293, 299, 377, 411 Rhinitis, 200, 411 Rhodopsin, 392, 411 Ribavirin, 192, 411 Ribose, 63, 174, 318, 411 Ribosome, 411, 424 Rickets, 318, 333, 411, 429 Rigidity, 185, 400, 411 Risk factor, 26, 31, 34, 66, 74, 79, 80, 108, 111, 128, 136, 151, 210, 219, 230, 233, 254, 283, 284, 293, 370, 380, 403, 409, 411 Risk patient, 128, 148, 412 Ristocetin, 412, 427 Rituximab, 126, 412 Rod, 328, 329, 341, 405, 412

S Saliva, 384, 412 Salivary, 25, 347, 348, 350, 395, 412, 418 Salivary glands, 347, 348, 350, 412 Saphenous, 39, 345, 412 Saphenous Vein, 39, 345, 412 Saponins, 412, 417 Sarcoidosis, 252, 412 Sarcoma, 232, 412 Scans, 155, 412 Schizoid, 412, 429 Schizophrenia, 204, 412, 429 Schizotypal Personality Disorder, 412, 429 Sciatica, 298, 412 Scleroderma, 172, 198, 413 Sclerosis, 33, 162, 172, 198, 274, 275, 387, 413 Screening, 22, 33, 47, 90, 123, 148, 235, 243, 254, 286, 293, 341, 413, 426 Scrub Typhus, 86, 413 Secretion, 162, 170, 178, 233, 237, 242 Secretory, 46, 75, 118, 413 Sediment, 191, 413, 426 Segmental, 122, 145, 363, 413, 416 Segmentation, 59, 413 Segregation, 329, 408, 413 Seizures, 136, 348, 356, 395, 398, 413, 417 Selenium, 239, 413 Sella, 400, 413 Semen, 404, 413 Seminoma, 352, 413 Semisynthetic, 335, 337, 338, 371, 394, 399, 413 Senescence, 174, 413 Senile, 162, 393, 413 Sepsis, 11, 16, 20, 37, 121, 162, 171, 197, 231, 413 Septic, 11, 37, 58, 83, 112, 116, 126, 174, 175, 327, 413 Septicemia, 66, 413 Sequence Homology, 397, 414 Serine, 30, 70, 184, 347, 354, 404, 414 Serotonin, 390, 414, 425 Serous, 355, 414 Serum Albumin, 12, 21, 28, 73, 402, 414 Sex Characteristics, 319, 322, 406, 414, 421 Sex Determination, 275, 414 Shedding, 75, 414 Shiga Toxin, 71, 85, 414 Shivering, 414, 421 Shock, 12, 37, 83, 87, 116, 171, 172, 174, 175, 197, 371, 414, 424

451

Side effect, 79, 145, 152, 155, 182, 192, 246, 259, 264, 285 Sigmoidal, 29, 414 Signal Transduction, 76, 334, 414 Signs and Symptoms, 284, 400, 409, 415, 426 Silicon, 239, 415 Silicon Dioxide, 415 Skeletal, 67, 125, 148, 174, 234, 323, 341, 386, 387, 411, 415, 424 Skeleton, 176, 209, 318, 377, 403, 415 Skin Aging, 174, 415 Skin test, 153, 415, 425 Skull, 194, 346, 415, 420 Small intestine, 337, 340, 352, 369, 371, 375, 377, 415 Smooth muscle, 30, 35, 40, 70, 178, 180, 185, 195, 199, 203, 206, 321, 322, 328, 333, 334, 369, 387, 404, 410, 415, 419 Sneezing, 414, 415 Social Behavior, 203, 415 Social Environment, 407, 415 Social Isolation, 15, 412, 415 Social Security, 216, 284, 408, 415 Social Support, 77, 415, 418 Social Work, 282, 283, 415 Soft tissue, 243, 332, 415, 416 Solid tumor, 152, 323, 416 Solvent, 329, 357, 364, 393, 398, 416 Somatic, 319, 369, 385, 397, 416 Sound wave, 343, 416, 425 Spatial disorientation, 351, 416 Specialist, 23, 146, 306, 350, 416 Species, 39, 52, 65, 210 Specificity, 76, 319, 334, 354, 416, 423 Spectrum, 30, 45, 240, 371, 386, 416 Sperm, 322, 340, 362, 416 Spinal cord, 162, 332, 336, 338, 339, 361, 383, 389, 390, 395, 397, 416, 418, 419 Spinal Cord Diseases, 395, 416 Spinal Nerve Roots, 413, 416 Spinal Nerves, 397, 416 Spleen, 252, 322, 347, 381, 395, 412, 417 Spondylolisthesis, 287, 417 Sporadic, 389, 411, 417 Sprains and Strains, 380, 417 Stabilization, 205, 399, 417 Staging, 412, 417 Standard therapy, 38, 417 Stasis, 71, 417 Status Epilepticus, 251, 417 Steel, 341, 417, 427

Stem cell transplantation, 93, 110, 417 Stem Cells, 81, 320, 357, 365, 417 Stenosis, 35, 242, 254, 417, 418 Sterile, 327, 395, 417, 425 Sterility, 347, 373, 417 Sternum, 194, 417 Steroid, 253, 346, 364, 412, 417 Steroid therapy, 253, 417 Stimulants, 229, 417 Stimulus, 162, 181, 189, 210, 344, 353, 357, 376, 417, 421 Stool, 82, 342, 373, 378, 418 Strand, 142, 174, 401, 418 Streptococcal, 25, 418 Streptococcus, 25, 418 Stress management, 217, 418 Stress Ulcer, 292, 418 Stricture, 417, 418 Stromal, 332, 418 Stromal Cells, 332, 418 Subacute, 373, 418 Subarachnoid, 366, 418 Subclavian, 254, 328, 418 Subclavian Artery, 418 Subclavian Vein, 254, 328, 418 Subclinical, 124, 128, 234, 373, 413, 418 Subcutaneous, 126, 127, 319, 353, 395, 418 Submaxillary, 356, 418 Subspecies, 416, 418 Substance P, 384, 408, 412, 413, 419 Substrate, 62, 174, 199, 200, 211, 356, 360, 419 Sucralfate, 135, 419 Suction, 359, 419 Sulfur, 358, 378, 384, 419 Superoxide, 167, 419 Superoxide Dismutase, 167, 419 Supplementation, 62, 64, 89, 183, 217, 229, 234, 240, 283, 419 Supportive care, 49, 419 Suppositories, 361, 419 Suppression, 51, 68, 346, 419 Suppressive, 162, 419 Supraventricular, 172, 198, 211, 419 Survival Analysis, 216, 419 Survival Rate, 205, 419 Sweat, 349, 384, 419 Sympathetic Nervous System, 199, 323, 328, 419, 420 Sympathomimetic, 351, 356, 390, 420 Symphysis, 339, 404, 420 Symptomatic, 44, 235, 395, 420

452 Renal failure

Synapse, 319, 389, 402, 420, 424 Synaptic, 390, 415, 420 Synergistic, 56, 68, 420 Systemic disease, 61, 413, 420 Systemic lupus erythematosus, 42, 287, 324, 325, 381, 420 Systolic, 19, 114, 173, 197, 295, 296, 297, 371, 420 T Tacrolimus, 151, 420 Technetium, 128, 420 Teicoplanin, 84, 420 Telangiectasia, 275, 420 Temporal, 30, 32, 51, 366, 381, 420 Teratogenic, 350, 420 Teratoma, 340, 420 Terminator, 350, 420, 430 Testis, 340, 352, 357, 364, 420 Testosterone, 408, 421 Tetany, 395, 421 Tetracycline, 60, 421 Thalamic, 327, 421 Thalamic Diseases, 327, 421 Thalassemia, 330, 421 Thalidomide, 128, 421 Theophylline, 210, 321, 406, 421 Therapeutics, 62, 110, 178, 264, 421 Thermogenesis, 210, 421 Third Ventricle, 371, 421 Thoracic, 88, 128, 288, 328, 349, 418, 421 Thorax, 317, 381, 421 Threonine, 30, 184, 397, 404, 414, 421 Threshold, 27, 38, 52, 189, 371, 421 Thrombectomy, 254, 353, 422 Thrombin, 359, 400, 404, 422 Thrombocytes, 400, 422 Thrombocytopenia, 36, 116, 288, 422 Thromboembolism, 289, 303, 422 Thrombomodulin, 404, 422 Thrombopenia, 325, 422 Thromboses, 325, 422 Thrombosis, 35, 36, 122, 150, 175, 178, 180, 201, 203, 254, 374, 405, 418, 422 Thromboxanes, 326, 404, 422 Thrombus, 345, 373, 387, 388, 400, 422 Thymidine, 46, 126, 333, 422 Thymus, 372, 381, 422 Thyroid, 334, 371, 376, 395, 422, 425 Thyroid Gland, 371, 395, 422 Thyroxine, 320, 398, 422 Time Management, 418, 422

Tissue, 37, 40, 42, 43, 45, 49, 51, 52, 60, 69, 70, 71, 72, 81, 151, 153, 165, 169, 170, 174, 182, 194, 195, 200, 252, 256, 285 Tissue Culture, 422, 428 Tissue Distribution, 45, 422 Tolerance, 50, 144, 146, 147, 156, 184, 236, 238, 318, 363, 423 Tomography, 95, 124, 343, 412, 423 Tone, 45, 390, 394, 423 Tonicity, 367, 423 Tonus, 423 Tooth Preparation, 318, 423 Topical, 82, 327, 357, 370, 384, 423 Topoisomerase inhibitors, 376, 423 Torsion, 373, 423 Total pancreatectomy, 395, 423 Toxicity, 39, 126, 134, 174, 179, 219, 352, 382, 384, 412, 419, 423 Toxicology, 51, 62, 69, 108, 124, 272, 423 Toxin, 36, 39, 44, 49, 61, 71, 75, 85, 190, 355, 414, 423 Trabecular Meshwork, 185, 423 Trace element, 239, 340, 415, 423 Tracer, 32, 59, 423 Traction, 341, 423 Transcriptase, 350, 378, 423, 430 Transcription Factors, 410, 423 Transdermal, 202, 203, 423 Transduction, 76, 414, 424 Transfection, 330, 353, 362, 424 Transfer Factor, 372, 424 Transforming Growth Factor beta, 57, 408, 424 Transfusion, 151, 301, 424 Translation, 77, 162, 168, 321, 424 Translational, 67, 162, 424 Transmitter, 317, 351, 376, 383, 390, 424 Trauma, 162, 174, 175, 177, 197, 296, 302, 348, 357, 395, 424 Tremor, 204, 274, 424 Tricuspid Atresia, 345, 424 Tricyclic, 178, 424 Triglyceride, 19, 201, 371, 424 Tropomyosin, 387, 424 Troponin, 82, 124, 387, 424 Trypanosomiasis, 396, 425 Tryptophan, 342, 399, 414, 425 Tube-feeding, 169, 425 Tubercle, 425 Tuberculin, 153, 289, 425 Tuberculin Test, 289, 425 Tuberous Sclerosis, 275, 425

453

Tumor marker, 330, 425 Tumor Necrosis Factor, 34, 75, 162, 421, 425 Type 2 diabetes, 22, 24, 31, 92, 100, 115, 240, 286, 288, 300, 425 Tyrosine, 51, 351, 405, 425 U Ubiquitin, 58, 425 Ulcer, 19, 135, 175, 232, 292, 418, 419, 425 Ulceration, 232, 396, 425 Ultrafiltration, 188, 195, 228, 230, 367, 425 Ultrasound test, 91, 425 Ultraviolet radiation, 415, 425 Unconscious, 323, 348, 371, 426 Uraemia, 395, 426 Uranium, 420, 426 Uranyl Nitrate, 84, 98, 426 Urea, 13, 19, 22, 25, 28, 62, 136, 179, 188, 190, 211, 241 Uremia, 19, 81, 171, 190, 217, 228, 230, 231, 233, 235, 239, 377, 409, 426 Ureter, 30, 81, 370, 377, 409, 426 Urethra, 396, 404, 426 Uric, 43, 167, 364, 371, 406, 426 Urinalysis, 148, 426 Urinary tract, 30, 134, 191, 287, 295, 329, 337, 426 Urinary tract infection, 287, 295, 329, 426 Urography, 223, 426 Urologist, 227, 426 Urology, 115, 227, 236, 284, 426 Uterus, 200, 317, 345, 383, 393, 403, 427 V Vaccination, 14, 98, 110, 129, 286, 427 Vaccine, 14, 61, 105, 115, 149, 182, 250, 319, 405, 427 Vacuoles, 354, 427 Vagina, 200, 335, 349, 383, 427 Vaginal, 185, 200, 381, 427 Vanadium, 239, 427 Vancomycin, 256, 427 Varicella, 14, 129, 427 Vascular, 16, 19, 20, 26, 30, 34, 35, 36, 37, 38, 40, 49, 52, 55, 57, 66, 68, 78, 94, 103, 113, 125, 127, 129, 143, 149, 150, 165, 172, 174, 177, 178, 180, 184, 185, 194, 195, 196, 197, 198, 199, 200, 201, 203, 215, 220, 232, 238, 240, 249, 254, 279, 301, 321, 323, 334, 340, 345, 349, 355, 366, 370, 373, 380, 385, 390, 400, 404, 416, 422, 427

Vascular endothelial growth factor, 68, 427 Vascular Resistance, 178, 180, 185, 203, 427 Vasculitis, 171, 395, 400, 427 Vasoactive, 36, 37, 71, 129, 175, 198, 199, 200, 427 Vasoactive Intestinal Peptide, 175, 427 Vasoconstriction, 38, 199, 207, 212, 356, 427 Vasodilation, 99, 185, 200, 207, 223, 323, 359, 427 Vasodilator, 12, 37, 71, 169, 209, 325, 332, 351, 369, 370, 388, 390, 427 Vasopressor, 38, 427 VE, 179, 427 Vector, 61, 160, 424, 427 Vein, 35, 113, 153, 254, 323, 327, 376, 391, 395, 412, 418, 427 Venous, 35, 185, 200, 289, 303, 325, 327, 328, 331, 378, 405, 424, 427 Venous blood, 331, 378, 427 Ventilation, 100, 410, 428 Ventricle, 65, 327, 345, 385, 406, 420, 421, 424, 428 Ventricular, 40, 102, 114, 128, 172, 180, 198, 211, 295, 297, 345, 388, 424, 428 Ventricular Dysfunction, 172, 198, 428 Venules, 331, 335, 355, 385, 428 Verapamil, 172, 263, 428 Vertebrae, 194, 375, 416, 428 Vesicular, 333, 428 Veterinary Medicine, 271, 428 Vibrio, 61, 339, 428 Vibrio cholerae, 61, 339, 428 Vimentin, 75, 428 Viral, 15, 113, 153, 184, 317, 350, 359, 363, 373, 392, 424, 428, 430 Viral Load, 153, 428 Virulence, 75, 423, 428 Virus, 14, 15 Visceral, 94, 285, 328, 378, 398, 428 Viscosity, 169, 317, 428 Visual field, 125, 392, 405, 428 Vitamin A, 205, 411, 428 Vitamin D, 129, 130, 190, 229, 232, 240, 242, 263, 411, 428 Vitreous, 349, 410, 429 Vitreous Body, 410, 429 Vitreous Hemorrhage, 349, 429 Vitro, 29, 40, 49, 53, 55, 61, 62, 66, 68, 69, 195, 368, 429

454 Renal failure

Vivo, 29, 38, 40, 41, 45, 47, 48, 55, 60, 61, 62, 73, 82, 176, 181, 195, 350, 362, 368, 373, 385, 394, 420, 422, 429 W Weight Gain, 210, 429 White blood cell, 37, 40, 151, 153, 194, 317, 324, 373, 378, 381, 386, 387, 390, 400, 429 Withdrawal, 293, 305, 348, 429 Womb, 427, 429 Wound Healing, 165, 231, 337, 374, 429 X Xanthine, 167, 429 Xanthine Oxidase, 167, 429

Xenobiotics, 53, 429 Xenograft, 324, 429 X-ray, 59, 148, 153, 155, 327, 332, 343, 344, 360, 361, 376, 382, 391, 407, 412, 429 X-ray therapy, 376, 429 Y Yeasts, 360, 398, 429 Z Zalcitabine, 378, 429 Zoster, 14, 368, 430 Zygote, 343, 344, 430 Zymogen, 404, 430

455

456 Renal failure