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

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

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CHRONIC 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., 1960Chronic Renal 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: 0-497-00255-8 1. Chronic 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 chronic 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 .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CHRONIC RENAL FAILURE ....................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Chronic Renal Failure................................................................. 27 E-Journals: PubMed Central ....................................................................................................... 84 The National Library of Medicine: PubMed ................................................................................ 86 CHAPTER 2. NUTRITION AND CHRONIC RENAL FAILURE ........................................................... 131 Overview.................................................................................................................................... 131 Finding Nutrition Studies on Chronic Renal Failure................................................................ 131 Federal Resources on Nutrition ................................................................................................. 132 Additional Web Resources ......................................................................................................... 133 CHAPTER 3. ALTERNATIVE MEDICINE AND CHRONIC RENAL FAILURE ..................................... 135 Overview.................................................................................................................................... 135 National Center for Complementary and Alternative Medicine................................................ 135 Additional Web Resources ......................................................................................................... 144 General References ..................................................................................................................... 146 CHAPTER 4. DISSERTATIONS ON CHRONIC RENAL FAILURE ....................................................... 147 Overview.................................................................................................................................... 147 Dissertations on Chronic Renal Failure..................................................................................... 147 Keeping Current ........................................................................................................................ 148 CHAPTER 5. PATENTS ON CHRONIC RENAL FAILURE .................................................................. 149 Overview.................................................................................................................................... 149 Patents on Chronic Renal Failure.............................................................................................. 149 Patent Applications on Chronic Renal Failure .......................................................................... 160 Keeping Current ........................................................................................................................ 164 CHAPTER 6. BOOKS ON CHRONIC RENAL FAILURE ..................................................................... 165 Overview.................................................................................................................................... 165 Book Summaries: Federal Agencies............................................................................................ 165 Book Summaries: Online Booksellers......................................................................................... 168 Chapters on Chronic Renal Failure............................................................................................ 170 CHAPTER 7. MULTIMEDIA ON CHRONIC RENAL FAILURE........................................................... 183 Overview.................................................................................................................................... 183 Audio Recordings....................................................................................................................... 183 CHAPTER 8. PERIODICALS AND NEWS ON CHRONIC RENAL FAILURE........................................ 185 Overview.................................................................................................................................... 185 News Services and Press Releases.............................................................................................. 185 Newsletter Articles .................................................................................................................... 187 Academic Periodicals covering Chronic Renal Failure .............................................................. 189 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 191 Overview.................................................................................................................................... 191 U.S. Pharmacopeia..................................................................................................................... 191 Commercial Databases ............................................................................................................... 192 Researching Orphan Drugs ....................................................................................................... 192 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 197 Overview.................................................................................................................................... 197 NIH Guidelines.......................................................................................................................... 197 NIH Databases........................................................................................................................... 199 Other Commercial Databases..................................................................................................... 201 APPENDIX B. PATIENT RESOURCES ............................................................................................... 203 Overview.................................................................................................................................... 203

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Patient Guideline Sources.......................................................................................................... 203 Finding Associations.................................................................................................................. 209 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 211 Overview.................................................................................................................................... 211 Preparation................................................................................................................................. 211 Finding a Local Medical Library................................................................................................ 211 Medical Libraries in the U.S. and Canada ................................................................................. 211 ONLINE GLOSSARIES................................................................................................................ 217 Online Dictionary Directories ................................................................................................... 223 CHRONIC RENAL FAILURE DICTIONARY.......................................................................... 225 INDEX .............................................................................................................................................. 309

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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 chronic 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 chronic 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 chronic 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 chronic 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 chronic 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 chronic 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 CHRONIC RENAL FAILURE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on chronic 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 chronic 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 “chronic 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: •

Quality of Prereferral Care in Patients with Chronic Renal Insufficiency Source: American Journal of Kidney Diseases. 40(1): 30-36. 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: Appropriate care in chronic renal insufficiency (CRI) includes blood pressure and diabetes control, as well as the investigation and management of anemia, acidosis, and bone disease. There is a lack of data on the control of these parameters at the time of referral to a nephrologist. Similarly, early referral has been emphasized in the literature, yet very little published has examined current referral patterns. This article reports on a review of all new outpatient referrals to nephrologists in Halifax,

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Canada in 1998 and 1999; the review was conducted to identify patients with CRI. Quality of pre-referral care was based on data from the initial clinic visit. Of 1,050 charts reviewed, 411 patients met the study criteria. Twenty-six percent of patients had diabetes mellitus, 18 percent were referred with a calculated glomerular filtration rate (GFR) less than 15 milliliters per minute, and blood pressure was optimally controlled in only 24 percent. Only 44 percent of patients were administered an ACE inhibitor. Patients were administered an average of 1.9 antihypertensive agents. Significant anemia was present in 21 percent and appropriate investigations (diagnostic tests) were performed in only 35 percent of these patients. Calcium levels less than 8.6 milligrams per deciliter were found in 19 percent of patients, and only 14 percent of these patients were started on calcium supplement therapy. Phosphate levels greater than 5.0 milligrams per deciliter were seen in 20 percent of patients, and 14 percent of these patients were on phosphate-binder therapy. Parathyroid hormone levels were more than five times normal values in 18 percent of patients. The authors conclude that a significant proportion of patients referred with CRI receive inadequate pre-referral care. Continuing education programs and referral guidelines must not only emphasize the importance of early referral, but also address the related consequences of CRI to delay the progression of renal (kidney) disease and avoid complications. 3 tables. 34 references. •

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 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.

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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.

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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. •

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 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.

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Survival Improvement Among Patients with End-Stage Renal Disease: Trends over Time for Transplant Recipients and Wait-Listed Patients Source: JASN. Journal of the American Society of Nephrology. 12(6): 1293-1296. June 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: Both kidney transplant and dialysis outcomes have improved over recent years. In addition, transplantation has been shown to confer a survival benefit over

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maintenance dialysis. This article reports on a study undertaken to determine whether the survival benefit of transplantation over maintenance dialysis has changed in the most recent eras. The study was based on data collected by the United States Renal Transplant Scientific Registry and the United States Renal Data System (USRDS). The study sample consisted of 104,000 patients placed on the renal transplant waiting list between 1988 and 1996, of which 73,707 subsequently received renal transplants. Overall annual adjusted death rates in the wait listed patients and transplant recipients per 1000 patient years decreased for both groups throughout the study period. From 1989 to 1996, the relative risk (RR) for patient death had decreased by 30 percent for transplant recipients and 23 percent for waitlisted patients. Slope analysis of the cause specific mortality rates for cardiovascular disease and infection showed nearly equivalent, linear decreases for both groups. Mortality (death) rates have improved overall and by categories of major cause of death for both renal transplant recipients and patients on the renal transplant waiting list. These favorable trends most likely represent equal advances in transplantation, dialysis, and general medical care. 6 figures. 1 table. 16 references. •

Cardiovascular Disease in Chronic Renal Insufficiency Source: American Journal of Kidney Diseases. 36(6, Supplement 3): S24-S30. December 2000. 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: Cardiovascular illness is an important contributor to the morbidity of kidney disease. This article reviews the interplay of cardiovascular disease (CVD) in chronic renal insufficiency (CRI). The authors note that the spectrum of CVD in patients with CRI includes left ventricular hypertrophy (LVH) and dilatation, ischemic heart disease, and peripheral vascular disease. Both traditional and uremia-specific factors contribute to the occurrence and progression of cardiac disease in kidney patients. A growing body of recent evidence indicates that the processes contributing to CVD commence early in CRI, leading to concentric LVH, left ventricular dilatation, congestive heart failure, and ischemic heart disease. Many of the coexisting conditions that have been identified consistently as contributing to the burden of cardiovascular illness in renal populations can be modified through medical interventions. Specific therapies exist for hypertension (high blood pressure), anemia (low levels of hemoglobin in the blood, resulting in diminished oxygen carrying capacity), hyperparathyroidism, and dyslipidemia (dysfunctional amounts of lipids, or fats, in the blood). Studies to date have demonstrated that treatment of many of these factors, such as anemia and hypertension during end stage renal disease (ESRD), appear to benefit the cardiovascular system. Earlier intervention may offer the best opportunity to reduce the burden of illness in all groups of CRI patients. Identification of patients at the onset of kidney disease and attention to the known traditional and uremic risk factors are emerging as promising strategies. The authors conclude that long term interventional studies are needed to determine costs, benefits, and risks of such strategies. 1 figure. 2 tables. 28 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.

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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. •

Management of Chronic Renal Insufficiency: A Call for a Proactive Approach Source: Nephrology News and Issues. 15(3): 32, 35-39. February 2001. Contact: Available from Nephrology News and Issues Inc. 15150 North Hayden Road, Suite 101, Scottsdale, AZ 85260. (602) 443-4635. Summary: Chronic renal insufficiency (CRI) is associated with an extensive and complex set of physiologic consequences that can result in a number of comorbidities and complications. CRI leads to high incidences of anemia, left ventricular hypertrophy (LVH), congestive heart failure, metabolic bone disease, and malnutrition in patients reaching end stage renal disease (ESRD). This article reviews CRI and its major comorbid conditions, many of which are preventable. The author emphasizes those clinical data that demonstrate the need for a Renal Anemia Management Period (RAMP), defined as the critical time during CRI when anemia develops. The author presents a rationale for the early diagnosis and aggressive management of CRI related anemia. As one of the common manifestations of CRI, anemia is at least partially responsible for many of the debilitating clinical conditions that in the past were attributed to uremia. And despite these negative consequences, the anemia of CRI is often under recognized and undertreated. Data from the Health Care Financing Administration (HCFA) indicate that 51 percent of new dialysis patients have hematocrit levels below 28 percent, and 80 percent of these patients receive no treatment for anemia. In addition, treating the anemia of CRI can produce a marked improvement in quality of life (QOL) and systemic symptomatology. 4 figures. 2 tables. 44 references.

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Resistance Training to Counteract the Catabolism of a Low-Protein Diet in Patients with Chronic Renal Insufficiency Source: Annals of Internal Medicine. 135(11): 965-976. December 4, 2001. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Chronic renal insufficiency (CRI) leads to muscle wasting, which may be exacerbated by low-protein diets prescribed to delay or slow disease progression. Resistance training increases protein utilization and muscle mass. This article reports on a study undertaken to determine the efficacy of resistance training in improving protein utilization and muscle mass in patients with CRI treated with a low protein diet. Results that show that resistance exercise training can preserve lean body mass, nutritional

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status, and muscle function in patients with moderate chronic kidney disease. The study's results suggest that resistance training is a safe and effective countermeasure to the negative effects of protein restriction on muscle mass accretion, protein utilization, nutritional status, and muscle function in patients with chronic kidney disease. 3 figures. 4 tables. 43 references. •

Management of Patients with Chronic Renal Insufficiency in the Northeastern United States Source: JASN. Journal of the American Society of Nephrology. 12(7): 1501-1507. July 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: Comorbid conditions (other illnesses present at the same time) that develop during chronic renal insufficiency (CRI) contribute to the high morbidity (illness) and mortality (death) among patients with end stage renal disease (ESRD). Thus, appropriate management during CRI may lead to improved ESRD outcomes. This article reports on a retrospective cohort study that was performed to describe the management of patients with CRI. A total of 602 patients with CRI were seen between October 1994 and September 1998 at five nephrology (kidney specialty) outpatient clinics in the Boston area. The mean age of the patients was 63 years and 53 percent were male. At the first nephrology visit mean serum creatinine was 3.2 milligrams per deciliter (plus or minus 1.6 mg per dl), and mean predicted glomerular filtration rate (GFR, a measure of kidney function) was 22.3 milliliters per minute per 1.73 m squared. Laboratory tests for iron levels were performed in only 18 percent of patients, serum parathyroid hormone levels were obtained in only 15 percent, lipid studies were obtained in fewer than half, and among patients with diabetes, only 28 percent had a glycosylated hemoglobin level measured. A hematocrit (red blood cells level) less than 30 percent was present in 38 percent of the patients, and abnormal calcium phosphorus metabolism was noted in 55 percent. Only 59 percent of the patients who had hematocrit less than 30 percent received recombinant human erythropoietin (a hormone used to treat anemia). Among patients who received erythropoietin, only 47 percent received iron. ACE inhibitor use was recorded for only 65 percent of patients with diabetes (49 percent of patients overall). Among patients who were known to have progressed to ESRD, only 41 percent had permanent access placed before initiation of dialysis. The author concludes that there seems to be room for improvement in the management of patients with CRI, which could result in a slower rate of progression of CRI and reduced severity of comorbid conditions. 1 figure. 3 tables. 44 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

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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 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. •

Risks and Monitoring of Elevated Parathyroid Hormone in Chronic Renal Failure (A Review) Source: Dialysis and Transplantation. 30(3): 147-148, 150-152, 154-155. March 2001. Contact: Available from Dialysis and Transplantation, Attn.: Subscriptions. P.O. Box 10535, Riverton, NJ 08076. (800) 624-4196 or (609) 786-0871. Summary: Elevated serum parathyroid hormone (PTH) levels are common in patients with chronic renal (kidney) failure (CRF). If excess PTH secretion is not treated, it leads to full blown secondary hyperparathyroidism. Secondary hyperparathyroidism is associated with many damaging effects in patients with CRF, and PTH has been suggested as an important toxin of uremia. The article reviews the risks and monitoring of elevated PTH in CRF. Elevated PTH blood levels are best treated by therapeutic administration of vitamin D compounds, but therapy must be monitored carefully to avoid oversuppression of PTH. Monitoring PTH levels is complicated because of the variety of different PTH tests available, the limitations of these tests, and the necessity of interpreting PTH results on a number of variables. Regardless of the methodology, regular and frequent determinations of serum PTH, calcium, and phosphate levels are important in the management of CRF patients, especially if the patients are receiving vitamin D hormone replacement therapy. Titrating the dose of vitamin D based on PTH levels has been suggested as a useful practice to further ensure positive patient outcomes and reduce costs in the long run by preventing many of the more costly interventions necessary when advanced secondary hyperparathyroidism develops. 46 references.

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End-Stage Renal Disease: Are We Ready for an Emerging Epidemic? (editorial) Source: Postgraduate Medicine. 108(1): 13-15. July 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: End stage renal (kidney) disease (ESRD) has occupied a unique place in the U.S. health care system since 1972, when Social Security extended Medicare coverage to patients under age 65 with ESRD or chronic kidney failure who require dialysis or a kidney transplant. Since that time, more than a million such patients have entered the Medicare entitlement program. This editorial explores the readiness of the medical community to handle this emerging epidemic. The author discusses progress in reducing the rate of ESRD development in the United States; efforts that can further reduce the rate of kidney failure, primarily by concentrating on patients with chronic renal insufficiency in the period prior to dialysis or transplantation; and the growing role for primary care physicians in early recognition and treatment of patients with chronic renal insufficiency. The author contends that the decline in the number of specialists being trained in nephrology in the face of an increasing number of patients

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with ESRD raises questions as to the ability of health care providers to care for these patients in the future. One sidebar explains the role of the U.S. Renal Data System (USRDS), an agency that collects, analyzes, and distributes information about ESRD in the United States. 1 table. 2 references. •

Clinical Use of Growth Factors in Chronic Renal Failure Source: Current Opinion in Nephrology and Hypertension. 9(1): 5-10. January 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: Erythropoietin has been demonstrated to improve the quality of life in patients with chronic renal failure (CRF), and growth hormone has been approved for use in children with CRF and short stature as a growth promoting agent. Growth factors also have great therapeutic potential to improve glomerular function in the setting of CRF. This article reviews the clinical use of growth factors in CRF. End stage renal disease (ESRD) patients experience uremic symptoms including lethargy, fatigue, cold intolerance, and impotence (erectile dysfunction). The use of erythropoietin can lead to an enhanced sense of well being, with resolution of some of the symptoms of uremia in the pre ESRD and in the dialysis population. However, erythropoietin does not prevent growth retardation in children with ESRD. The authors review the clinical use of growth hormones, notably insulin like growth factor I (IGF-I), in this patient population. The IGF-I can be given to patients with reduced renal function in order to increase their glomerular filtration rate (GFR). When administered in this manner to individuals with ESRD for whom the initiation of dialysis was the next step, the IGF-I treatment can effect a progressive improvement of renal function. The authors report that dosing changes may be necessary to enhance the tolerability of the drug and to prevent side effects. The authors caution that one potential risk of long term therapy with growth hormone and IGF-I is glomerulosclerosis associated with hyperfiltration. IGF-I has also been implicated in certain malignancies (cancer). However, the authors conclude that the use of growth factors in the setting of CRF and ESRD has resulted in improved quality of life in both the adult and pediatric populations. 2 figures. 1 table. 49 references (3 annotated).

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Twenty-Eight-Year-Old Female with Primary Amenorrhea and Chronic Renal Failure: A Case of Frasier Syndrome? Source: Journal of the American Medical Association. 96(2): 256-261. February 2004. Summary: Frasier syndrome is a very rare developmental disorder of autosomal recessive inheritance. Frasier syndrome is characterized by male hermaphroditism, primary amenorrhea, chronic renal failure (CRF), and a number of other abnormalities. In this article, a 28 year old Nigerian female who was considered as a possible case of Frasier syndrome was described; she first presented to the authors in July 2002 with primary amenorrhea, congenital bilateral absence of middle toes, elevated blood pressure, and the uremic syndrome. The management of the case was mainly conservative, including blood pressure control with appropriate antihypertensives. The problems inherent in this index case are discussed while proffering appropriate management approach in a near-ideal situation, which unfortunately is nonexistent in the author's local environment (Nigeria). 10 references.

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Growth Failure, Risk of Hospitalization and Death of Children with End-stage Renal Disease Source: Pediatric Nephrology. 17(6): 450-455. June 2002. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: Growth failure remains a significant problem for children with chronic renal insufficiency and end stage renal disease (ESRD). This article reports on a study that examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. The authors studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990. Among 1,112 prevalent pediatric dialysis and transplant patients, those with severe and moderate growth failure had higher hospitalization rates respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality in 1990. Survival analysis showed 5 year survival rates of 85 percent and 90 percent for patients with severe and moderate growth failure, respectively, compared with 96 percent for patients with normal growth. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22 percent and 18.7 percent, respectively) than in the normal growth group (15.6 percent). The authors conclude that growth failure is associated with a more complicated clinical course and increased risk of death for children with kidney failure. 1 figure. 3 tables. 15 references.

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Improved Growth in Young Children with Severe Chronic Renal Insufficiency Who Use Specified Nutritional Therapy Source: JASN. Journal of the American Society of Nephrology. 12(11): 2418-2426. November 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: Growth in children with chronic renal (kidney) failure caused by polyuric, salt wasting diseases may be hampered if ongoing sodium and water losses are not corrected. This article reports on a study of 24 children with polyuric chronic renal insufficiency (CRI) who were treated with low-caloric-density, high volume, sodium supplemented feedings. Subsequent growth was compared with that of children in two control groups: a national historic population control from the U.S. Renal Data System database (n = 42) and a literature control (n = 12). Members of the three groups were 81 to 96 percent white, and 58 to 70 percent were boys. Obstructive uropathy and dysplasia (abnormal cell growth) were the cause of CRI in 92 percent of the treatment group, in 75 percent of the literature control group, and in 30 percent of the population control group. Treatment effect was assessed in a multivariate, retrospective analysis of the height standard deviation score (SDS), simultaneously controlling for the severity of disease by renal replacement therapy, primary cause of CRI, and initial height SDS. The change in standard deviation for height by regression analysis at 1 year was significantly greater in the treatment group versus the population control. Thus, the authors conclude that nutritional support with sodium and water supplementation can maintain or improve the growth of children with polyuric, salt-wasting CRI. This inexpensive intervention may delay the need for renal replacement therapy (such as dialysis), growth hormone treatment, or both in many of these children, and may be used in any clinical setting. 2 figures. 4 tables. 24 references.

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Does Recombinant Growth Hormone Improve Adult Height in Children with Chronic Renal Failure? Source: Seminars in Nephrology. 21(5): 490-497. September 2001. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Growth retardation is a frequent complication in children with chronic renal failure before and after renal (kidney) transplantation. During the past decade, the safety and efficacy of long term treatment with recombinant human growth hormone (rhGH) in children with chronic renal failure (CRF) has been established. This article reviews the increasing evidence that rhGH treatment also results in a significant improvement of adult height in patients with childhood onset CRF. The eventual height benefit of extended rhGH treatment appears to be 1.0 to 1.5 standard deviations on average. Whereas prepubertal rhGH treatment has a beneficial effect on final height, the efficacy of rhGH during puberty is less evident. The cumulative duration of rhGH treatment was found to be the most important positive, and the duration of dialysis treatment periods a negative predictor of rhGH efficacy, stressing the importance of prolonged rhGH treatment starting early in the course of CRF. Dialysis periods should be kept as short as possible. Although preemptive transplantation (before the child's kidneys fail) may be available only to a small subgroup of patients in many countries, active transplantation programs are an indispensable part of the strategy to improve final adult height in patients with childhood onset CRF. 3 figures. 1 table. 22 references.

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Prevention and Treatment of Renal Osteodystrophy in Children with Chronic Renal Insufficiency and End-Stage Renal Disease Source: Seminars in Nephrology. 21(5): 441-450. September 2001. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Histologic features associated with secondary hyperparathyroidism (overactive parathyroid gland) remain the predominant skeletal lesion in adults and children with chronic renal (kidney) failure. This article considers the prevention and treatment of renal osteodystrophy (bone disease associated with kidney disease) in children with chronic renal insufficiency (CRI) and end stage renal disease (ESRD). When instituted early, vitamin D therapy has been shown to slow the development and progression of the biochemical, radiographic, and histologic (cell structure) evidence of secondary hyperparathyroidism in patients with CRI. Aggressive parathyroid hormone suppression, however, has led to the increased prevalence of adynamic bone (bone that does not grow and change in response to the body's needs). Adynamic bone has been attributed partly to aggressive calcitriol therapy, administration of high amounts of exogenous calcium either as a phosphate binding agent or during dialysis therapy, presence of diabetes, older age, or previous parathyroidectomy (removal of the gland). Several vitamin D analogues are currently being evaluated in patients with chronic renal failure (CRF) to prevent complications associated with calcitriol therapy. In addition, calcium-free phosphate binding agents and the use of calcimimetic drugs may play a significant role in the effective management of secondary hyperparathyroidism in children with CRF. 2 figures. 73 references.

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Hypertension in Chronic Renal Failure and ESRD: Prevalence, Pathophysiology, and Outcomes Source: Seminars in Nephrology. 21(2): 146-156. March 2001. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Hypertension (high blood pressure) and cardiovascular diseases were detected to be major problems in end stage renal disease (ESRD) patients soon after chronic dialysis was first used to treat uremia (a condition caused by kidney disease that features an excess in the blood of urea, creatinine, and other end products of protein metabolism). Nearly 40 years later, and despite extensive technological and pharmacological advances, cardiovascular diseases remain the number one cause of death in all categories of renal (kidney) patients, including those with chronic renal insufficiency (reduced kidney function), end stage renal dialysis on dialysis, and the renal transplant recipient. This article explores the prevalence, pathophysiology, and outcomes of hypertension in chronic renal failure (CRF) and ESRD. These cardiovascular diseases are quite likely related to the massive clinical burden of cardiovascular risk factors: hypertension, cardiac fibrosis and hypertrophy (overgrowth), abnormal lipid profiles (such as cholesterol), smoking, dietary factors, and enhanced sympathetic activity. For example, left ventricular hypertrophy and abnormal echocardiograms are present in up to 75 to 80 percent of incident dialysis patients related to the interactions of these cardiovascular risks. Based on the latest national data from the United States Renal Data Service (USRDS), the prevalence of underlying cardiac disease is increasing during the period of CRF. Diagnostic tests may include ambulatory blood pressure monitoring, cardiac echocardiography, lipid profiles, angiography, and routine physical examinations. The authors stress that good blood pressure control leads to longer survival times for the ESRD patient. A proper understanding of the pathophysiology and prevalence of hypertension and its consequences in renal patients may lead to more rational therapies and clinical trials. 2 figures. 3 tables. 134 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,

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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. •

Impact of Calcium in Phosphorus Management: Excess Calcium Load in Chronic Renal Failure Adds Risk for Patients Source: Nephrology News and Issues. p. 17-28. November 2001. Contact: Available from Nephrology News and Issues Inc. 15150 North Hayden Road, Suite 101, Scottsdale, AZ 85260. (602) 443-4635. Summary: One of the many challenges in managing kidney failure is controlling serum (blood) phosphorus levels. As kidney function diminishes, the normal renal (kidney) excretion of phosphorus becomes impaired and excess phosphorus accumulates, leading to increased phosphate levels in the blood. Elevated serum phosphorus levels are dangerous: they can lead to secondary hyperparathyroidism, renal bone disease, metastatic calcification of the heart and other soft tissues, and possibly premature death. This article describes the impact of calcium in phosphorus management, explaining how excess calcium load in chronic renal failure (CRF) adds risk for patients. Keeping calcium and phosphorus in balance can reduce the risk of cardiovascular calcification, cardiovascular disease, and death. Recently, new target levels have been suggested for serum phosphorus, calcium, and a Ca x P (serum calcium-phosphorus product), which are lower than previous recommendations. The author notes that these target levels can be achieved in most patients if new strategies for phosphorus management are adopted. These strategies include using calcium-free phosphate binders to control phosphorus levels without adding to the calcium load. The author concludes that it is important to recognize calcium content of the phosphate restricted renal diet can lead to calcium deficiency and osteoporosis. Some patients may benefit from a combination of calcium supplements (possibly as phosphate binders) and a calcium-free phosphate binder to achieve effective phosphate control with balanced calcium homeostasis. 50 references.

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Severity of Secondary Hyperparathyroidism in Chronic Renal Insufficiency is GFRDependent, Race-Dependent, and Associated with Cardiovascular Disease Source: JASN. Journal of the American Society of Nephrology. 13 (11): 2762-2769. November 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: Secondary hyperparathyroidism (SHPT) is an important complication of end stage renal disease (ESRD). However, SHPT begins during earlier stages of chronic renal insufficiency (CRI), and little is known about the risk factors for SHPT in this population. This article reports on a study of 218 patients at an ethnically diverse ambulatory nephrology practice at the University of California San Francisco during calendar years 1999 and 2000. Demographic data, comorbid diseases, medications, and laboratory parameters were collected, and independent correlates of intact parathyroid hormone (PTH) were identified. PTH was inversely related to GFR. The adjusted mean PTH was higher among African Americans and lower among Asian and Pacific Islanders compared with white patients. After adjusting for age and diabetes, PTH was associated with a history of myocardial infarction and congestive heart failure and not

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associated with other co-morbid conditions. These factors should be considered when screening and managing SHPT in CRI. 1 figure. 4 tables. 61 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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Acetaminophen, Aspirin, and Chronic Renal Failure Source: New England Journal of Medicine. 345(25): 1801-8. December 2001. Summary: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics (painkillers) and the occurrence of chronic renal (kidney) failure (CRF), but it is unclear which is the cause and which is the effect. This article reports on a nationwide, population-based, case-control study of early stage chronic renal failure in which face-to-face interviews were conducted with 926 patients with newly-diagnosed renal failure and 998 control subjects. Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with kidney failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic kidney failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. However, when the researchers disregarded the recent use of analgesics, which could have occurred in response to antecedents of kidney disease, the associations were only slightly attenuated. Therefore, the researchers cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions. 2 figures. 4 tables. 31 references.

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Current Concepts of Anemia Management in Chronic Renal Failure: Impact of NKFDOQI Source: Seminars in Nephrology. 20(4): 320-329. July 2000. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Since the introduction of recombinant human erythropoietin (rHuEPO) into clinical nephrology practice 10 years ago, there has been a slow increase in hemoglobin

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(Hgb) levels. However, most patients with the anemia of chronic renal (kidney) failure (CRF) are still moderately anemic and have not achieved the target Hgb (11 to 12 grams per dL) recommended by the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF DOQI) anemia guidelines. This article reviews current concepts for anemia management in patients with CRF. The author notes that functional iron deficiency, insufficient rHuEPO doses, and comorbid factors such as inflammation or infection have been the major reasons for not achieving this target. By optimizing iron stores with regular infusions of intravenous iron in the hemodialysis patient (who has significant blood iron losses related to the hemodialysis procedure) and giving adequate amounts of rHuEPO, preferably subcutaneously instead of intravenously, the NKF DOQI recommended target Hgb can be achieved in the majority of patients so treated. The author comments that the role of 'underdialysis' (dialysis inadequacy) as a cause of less than optimal responsiveness to rHuEPO remains controversial. Other unresolved issues include the role of ACE inhibitors and carnitine in the management of patients using rHuEPO. Periodic monitoring of Hgb (e.g., every 2 to 4 weeks) and of iron parameters (e.g., every 3 months) is essential to optimize anemia management. 2 figures. 2 tables. 47 references. •

Improvement of Sleep Apnea in Patients with Chronic Renal Failure Who Undergo Nocturnal Hemodialysis Source: New England Journal of Medicine. 344(2): 102-107. January 11, 2001. Summary: Sleep apnea (defined as the absence of airflow for longer than 10 seconds; it usually interrupts sleep) is common in patients with chronic renal failure (CRF) and is not improved by either conventional hemodialysis of peritoneal dialysis. With nocturnal hemodialysis, patients undergo hemodialysis seven nights per week at home, while sleeping. This article reports on a study undertaken to investigate the role of nocturnal hemodialysis in correcting sleep apnea in patients with CRF. Fourteen patients who were undergoing conventional hemodialysis for four hours on each of three days per week underwent overnight polysomnography (a measurement of sleep). The patients were then switched to nocturnal hemodialysis for eight hours during each of six or seven nights a week. They underwent polysomnography again 6 to 15 months later on one night when they were undergoing nocturnal hemodialysis and on another night when they were not. The mean serum creatinine concentration (a measurement of kidney or replacement kidney function) was significantly lower during the period when the patients were undergoing nocturnal hemodialysis than during the period when they were undergoing conventional hemodialysis. The conversion from conventional hemodialysis to nocturnal hemodialysis was associated with a reduction in the frequency of apnea and hypopnea from 25 (plus or minus 25) to 8 (plus or minus 8) episodes per hour of sleep. This reduction occurred predominantly in seven patients with sleep apnea, in whom the frequency of episodes fell from 46 (plus or minus 19) to 9 (plus or minus 9) episodes per hour, accompanied by increases in the minimal oxygen saturation, transcutaneous partial pressure of carbon dioxide, and serum bicarbonate concentration. During the period when these seven patients were undergoing nocturnal hemodialysis, the apnea hypopnea index measured on nights when they were not undergoing nocturnal hemodialysis was greater than that on nights when they were undergoing nocturnal hemodialysis, but it still remained lower than it had been during the period when they were undergoing conventional hemodialysis. The authors conclude that nocturnal hemodialysis corrects sleep apnea associated with chronic renal failure. 2 figures. 4 tables. 22 references.

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Early Education of Patients with Chronic Renal Insufficiency: The Healthy Start Program: Case Study of the Anemic Patient Source: Nephrology Nursing Journal. 28(6): 643-646. December 2001. Contact: Available from American Nephrology Nurses' Association. East Holly Avenue, Box 56, Pitman, NJ 08071-0056. (856) 256-2320. Fax (856) 589-7463. Website: www.annanurse.org. Summary: The Healthy Start Clinic is a multidisciplinary program that provides education and appropriate clinical interventions for patients with chronic renal (kidney) insufficiency (CRI). The overall goals of the program are to delay the progression of kidney disease and improve the quality of care at the initiation of renal replacement therapy (dialysis or transplantation). This article reports on a study undertaken to determine whether the Healthy Start program affected indicators of quality of care at initiation of dialysis. Patients who were enrolled in the program and who initiated dialysis between August 1997 and June 1999 were assessed (n = 57). The results show that, compared to those who do not participate in the program, Healthy Start patients have significantly higher albumin levels and are more likely to have fistulas in place at the initiation of dialysis. The Healthy Start model suggests a new and expanded role for nurses in helping to coordinate care for this growing patient population. The author stresses that nephrology nurses, working in concert with a multidisciplinary nephrology team and in partnership with the primary care physician, can significantly modify factors known to result in improved patient outcomes. 3 figures. 2 tables. 9 references.

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Preventing Hepatitis B and Hepatitis C Virus Infections in End-Stage Renal Disease Patients: Back to Basics (editorial) Source: Hepatology. 29(1): 291-293. January 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The impact of hepatitis B (HBV) and C (HCV) on patient survival after kidney transplantation is controversial. This article comments on a study published in the journal that assessed the independent prognostic values of HBsAg and anti-HCV in a large renal transplant population. At 10 years, among all patients with HCV screening (n = 834), 4 variables had independent prognostic values in patient survival: age at transplantation, year of transplantation, biopsy proven cirrhosis, and presence of HCV antibodies. The authors of the commentary note that the findings of the study underscore the importance of preventing hepatitis B and C virus infections in end stage renal disease (ESRD). Patients with ESRD on chronic hemodialysis are at risk for both HBV and HCV infection, despite the success of longstanding infection control practices in the dialysis setting. The authors consider the reasons why infection control strategies are no longer universally implemented and discuss routine hemodialysis unit precautions that could prevent transmission of HBV if the precautions are routinely and rigorously followed. The transmission of HCV infection among chronic hemodialysis patients also might be related to failure to follow routine hemodialysis unit precautions. The authors conclude by reiterating that those responsible for the care of chronic hemodialysis patients should reacquaint themselves with the recommendations for preventing bloodborne pathogen transmission in this setting and ensure that they are performed. 17 references.

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Anemia Management in Patients with Chronic Renal Insufficiency Source: American Journal of Kidney Diseases. 36(6, Supplement 3): S39-S51. December 2000. 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: The introduction of recombinant human erythropoietin (rHuEPO) more than a decade ago provided the first effective treatment for the anemia associated with chronic renal (kidney) insufficiency (CRI). Despite evidence of the positive impact of rHuEPO, the anemia of CRI remains highly prevalent, underrecognized, and undertreated. This article reviews the rationale for treatment of anemia, current management practices, proposed treatment strategies, and the economic implications of improved anemia treatment. The benefits of correction of anemia include significant improvements in health related quality of life, overall well being, energy level, work capacity, aerobic capacity, cognitive function, sexual function, and immune function; a decrease in the requirement for blood transfusions; and evidence of reduction in cardiovascular complications. The current practice guidelines recommend that patients with CRI and anemia should be investigated and treated for iron deficiency and other causes of anemia. The aggressive approach of investigation and treatment of anemia as soon as the hematocrit drops below the normal range is the ideal strategy; however, third party payers in the United States do not begin to cover the cost of rHuEPO until the hematocrit level has fallen below 30 percent. The authors conclude that the cost of treating the large population of patients with CRI and anemia in the United States with rHuEPO would undoubtedly be high. However, the reduced cardiovascular disease burden related to improved anemia management, and the deferred cost of dialysis, may offset the high cost of rHuEPO. 1 figure. 2 tables. 110 references.

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Clinical Efficacy of Higher Hematocrit Levels in Children with Chronic Renal Insufficiency and Those Undergoing Dialysis Source: Seminars in Nephrology. 21(5): 451-462. September 2001. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: The optimal hematocrit (the measurement used to determine the volume of red blood cells, i.e., the ability of the blood to carry oxygen) target range in children with end stage renal disease (ESRD), who are receiving recombinant human erythropoietin, is ambiguous due to the lack of compelling, age appropriate studies. This article explores the clinical effectiveness of higher hematocrit levels in children with chronic renal insufficiency (CRI) and in those undergoing dialysis. There are many adult and pediatric studies which show that physical performance as well as morbidity (associated illness) and mortality (death) are positively influenced by partial normalization of the hematocrit to 30 volume percent to 35 volume percent. Cognition studies performed in adults similarly show improvement with partial correction of hematocrit. Normalization of hematocrit studies show lower mortality rates, incremental further improvement in cognition, and greater resolution of cardiac (heart) anomalies when compared with patients with partial correction of anemia. Conversely, cardiac death rates may increase in adult patients receiving hemodialysis who have preexisting cardiac disease, and there are concerns about the effect of recombinant human erythropoietin on catheter or shunt or fistula patency and on blood pressure. The authors stress that the rationale of using adult derived hematocrits in children with ESRD needs to be reexamined in the context

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of the unique growth and developmental requirements of children. 1 table. 140 references. •

Anemia: An Early Complication of Chronic Renal Insufficiency Source: American Journal of Kidney Diseases. 38(4): 803-812. October 2001. 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: The strong association between anemia (low levels of oxygen carrying cells, hemoglobin, in the blood) and cardiovascular complications among patients with end stage renal disease (ESRD) suggests that anemia during chronic renal (kidney) insufficiency (CRI) may also have important consequences. This article reports on a retrospective cohort study undertaken to identify factors associated with severe anemia (hematocrit or Hct less than 30 percent) and to examine anemia management practices in CRI. The CRI cohort was composed of 604 adult patients with elevated serum creatinine levels (a blood test that measures kidney function). There was a direct correlation between predicted glomerular filtration rate (GFR) and hematocrit in CRI; 45 percent of patients with serum creatinine levels of 2 milligrams per deciliter or less had an Hct less than 36 percent, and 8 percent had an Hct less than 30 percent. During the course of the study, mean Hct decreased from 35.1 percent (plus or minus 5.6 percent) to 31.8 percent (plus or minus 5.6 percent). Iron studies were obtained in only 19 percent of patients, and among these, the prevalence of iron deficiency was 53 percent. Only 30 percent of patients were administered recombinant human erythropoietin (rHuEPO), and 26 percent of patients were administered iron. Multivariate analyses showed that diabetes as the cause of renal disease, greater serum creatinine level, and having a single nephrology (kidney specialist) visit were associated with greater odds for rHuEPO use. These results show that anemia begins early in the course of CRI, and present management of anemia is suboptimal, even among patients under the care of nephrologists. The authors also call for educational programs to optimize anemia management among patients with CRI. 3 figures. 5 tables. 32 references.

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Treating Chronic Renal Insufficiency: The Nephrologist vs. the Internist (a Commentary) Source: Dialysis and Transplantation. 29(8): 472-474. August 2000. Contact: Available from Dialysis and Transplantation, Attn.: Subscriptions. P.O. Box 10535, Riverton, NJ 08076. (800) 624-4196 or (609) 786-0871. Summary: The treatment of chronic renal insufficiency (CRI) is complex, and the objectives of care are often not well defined. This article helps to shed light on the blurred responsibilities and miscommunication that can result in failure to meet the basic health needs of patients with CRI. The author, a nephrologist, proposes more clear delineation of the respective roles of the internist and nephrologist, and offers a list of core objectives in the renal care of these patients. The author notes that various physicians may be involved in the care of patients with CRI, including nephrologists, primary care doctors, cardiologists, diabetologists, and others. In many cases, there may have been no contact with a nephrologist despite the presence of advanced renal disease. Patients frequently reach end stage renal disease (ESRD) with untreated anemia, no permanent access (for dialysis), no previous education on treatment choices, no visit with a dietitian, uncontrolled hypertension (high blood pressure), and advanced bone disease (osteodystrophy). The author contends that nephrologists must take a more active role in ensuring that patient care is improved. The author lists and describes

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11 core objectives of renal treatment of CRI: identification of potentially treatable causes of renal disease; intervention aimed at delaying disease progression; early identification and treatment of anemia; adequate treatment of hypertension; early identification and treatment of renal osteodystrophy; maintenance of good nutrition; identification and treatment of electrolyte and acid base disturbances; treatment of the patient's comorbid conditions (such as cardiac disease and diabetes); identification and intervention for psychosocial risk; appropriate disease education; and early modality (treatment) selection and vascular access placement. 4 references. •

Opportunities for Improving the Care of Patients with Chronic Renal Insufficiency: Current Practice Patterns Source: JASN. Journal of the American Society of Nephrology. 12(8): 1713-1720. August 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: There are between 2 and 13 million Americans with chronic kidney disease (CKD). Recent reports suggest that their treatment is currently suboptimal. This article reports on a study undertaken to investigate the patterns of health care practice for the treatment of patients with CKD who were enrolled in a large health maintenance organization in New Mexico. Among the greater than 200,000 patients who were enrolled in the health maintenance organization between 1994 and 1997, a cohort of 1,658 patients who exhibited at least two gender specific, elevated creatinine concentrations (Cr), separated by at least 90 days, was identified. The majority of patients were treated by a primary care physician until Cr values reached a set limit (3.0 milligrams per deciliter), at which time a nephrologist was consulted. Care tended to be transferred to the nephrologist when the Cr reached 4.0 mg per dl. Only 7.4 percent of patients received erythropoietin (EPO), a synthetic hormone that combats anemia and thus tends in increase patient quality of life. Use of EPO increased as Cr increased. EPO was unlikely to be prescribed unless the patient had visited a nephrologist. Fewer than one half of all patients with CKD and fewer than 20 percent of patients with CKD with Cr values greater than 4.0 mg per dl received an ACE (angiotensin converting enzyme) inhibitor. ACE inhibitors are antihypertensive (high blood pressure) drugs that have been shown to slow the progression of kidney disease. Nephrologists were not more likely to prescribe ACE inhibitors than were primary care physicians. Patients with diabetes were more likely to receive ACE inhibitors than were nondiabetic patients, but ACE inhibitors use was quite low even among diabetic patients with CKD. The average number of hospitalizations per patient year increased as Cr increased and was more than twice as high for patients with Cr values greater than 4.0 mg per dl, compared with those with Cr values of less than 2.0 mg per dl. The reasons for hospitalization were more likely to be related to comorbidities (other diseases present at the same time) than to CKD itself. The authors conclude that better adherence to practices known to be of clinical benefit for patients with CKD not only will improve patient outcomes but also may reduce the costs of care. 7 tables. 33 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:

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[email protected]. Website: www.pediatrics.org. Full text of this article is available at www.pediatrics.org/cgi/content/full/108/1/e5. 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, End-Stage Renal Disease, and Peritoneal Dialysis in Gitelman's Syndrome Source: American Journal of Kidney Diseases. 38(1): 165-168. July 2001. 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 article discusses chronic renal (kidney) failure, end stage renal disease (ESRD), and peritoneal dialysis in patients with Gitelman's syndrome. A related sydrome, Bartter's syndrome is characterized by hypovolemia (low volume of circulating blood), hypotension (low blood pressure), and hypokalemia (low levels of potassium in the blood), conditions which can lead to a chronic nephropathy (kidney disease) culminating in ESRD and dialysis. This progression, however, has never been reported for Gitelman's syndrome, a variant of Bartter's syndrome that shows a milder clinical picture. This article is the first to document this progression (i.e., the development of ESRD in Gitelman's syndrome) as well as the first report of the use of peritoneal dialysis in either Bartter's syndrome or Gitelman's syndrome. The clinical course highlights the importance of and the need for careful control of hemodynamic (blood system) status in these patients to slow the progression of renal injury. The hemodynamic alterations that characterize Bartter's syndrome and Gitelman's syndrome patients suggest that for patients requiring renal replacement therapy, peritoneal dialysis (with modification of dialysis solutions) is a more appropriate treatment because of its less severe impact on these parameters. 2 tables. 25 references.

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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.

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

Adaptive Response to a Low-Protein Diet in Predialysis Chronic Renal Failure Patients Source: JASN. Journal of the American Society of Nephrology. 12(6): 1249-1254. June 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: This article reports on a randomized, controlled study of 12 patients with mild chronic renal (kidney) failure that was designed to assess the metabolic effects of a low protein diet supplemented (n = 6) or not supplemented (n = 6) with ketoanalogs of amino acids. The protein intake was prescribed so that both groups were isonitrogenous (equal in nitrogen intake). The dietary survey each month included a 3 day food record and a 24 hour urine collection for urea measurement. After a 4 to 6 week equilibrium period (standard diet, 1.11 grams of protein and 32 kcal per kilogram of body weight per day), patients reduced their protein intake to reach 0.71 grams of protein per kilogram per day during the third month. Energy intake was kept constant during the 3 month period. Compliance to the diet was achieved after 2 months of training. Leucine turnover measurement was performed before and at the end of the 3 month low protein period. There was no clinical change, whereas total body flux decreased by 8 percent and leucine oxidation by 18 percent. No difference could be attributed to the ketoanalogs themselves. Thus, the authors conclude that under sufficient energy intake, a low protein diet is nutritionally and metabolically safe during chronic renal failure.

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The nitrogen sparing effect of a low protein diet is still present during mild chronic renal insufficiency. 1 figure. 4 tables. 29 references. •

Chronic Renal Failure and Periodontal Disease Source: Renal Failure. 22(3): 307-318. 2000. Contact: Available from Marcel Dekker Journals. P.O. Box 5017, Monticello, NY 127015176. (212) 696-9000. Summary: This article reports on a study of 6 patients (4 male, 2 female) with chronic renal failure (CRF) who were on chronic hemodialysis for an average of 4.25 years (range 1 to 15 years). The study was undertaken to define the effects of CRF in the progress of gingival inflammation. Six healthy individuals, age and sex matched, were used as controls. The protocol comprised two periods: a 40 day duration period of preparation and a 28 day duration experimental period. During the preparation period, all subjects went through therapy of the chronic gingivitis and complete control of dental plaque by oral hygiene. During the experimental period, all subjects were advised to avoid, for at least 21 days, any mechanical or chemical media of oral hygiene and went through photographing, recording of gingival index (GI), recording of plaque index (PlI) and the collection and quantification of gingival crevicular fluid (GCF). On the 21st day, root planing and polishing were performed and subjects were advised to carry out oral hygiene. On the 28th day, all previous examinations were repeated. Results showed that, in both patients and controls, GI, PlI, and GCF were increased on the 7th, 14th, and 21st day, without significant differences between the groups and returned to normal (close to zero point) on the 28th day. The authors conclude that there are no significant differences between patients with CRF and normal controls in the evolution of experimental gingivitis. Therefore, chronic uremia has no effect on the defense of periodontal tissue against microbial plaque. 4 figures. 7 tables. 31 references.

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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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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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Insulin-Like Growth Factor I Treatment for End-Stage Renal Disease at the End of the Millennium (editorial) Source: Current Opinion in Nephrology and Hypertension. 9(1): 1-3. January 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: This editorial commentary serves as an introduction to a review article published in the same issue. The author of the commentary summarizes the history and current status of the use of insulin like growth factor I (IGF-I) treatment for end stage renal disease (ESRD). Much of the research that elucidated the usefulness of IGF-I consists of animal studies. The research study reported in this same issue assessed the use of a lower IGF-I dose (because of concerns about side effects with higher doses) given on an intermittent basis (4 days per week) to eliminate resistance to the action of the drug. The IGF-I is given to patients with reduced renal function in order to increase their glomerular filtration rate (GFR). When administered in this manner to individuals with ESRD for whom the initiation of dialysis was the next step, the IGF-I treatment caused a progressive improvement of renal function over a period of 1 month. The author of the commentary reminds readers that the use of IGF-I in humans still includes some risk, including that of malignancy (cancer). No firm conclusions can be made on the basis of the small number of patients to whom IFG-I was given. However, given a choice between hemodialysis, peritoneal dialysis, or four injections per week of IGF-I, most patients would probably choose the IGF-I. 20 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.

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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. •

Hypertension in End-Stage Renal Disease Patients Source: Current Opinion in Nephrology and Hypertension. 9(3): 279-283. May 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: This review article discusses the prevalence, impact, and treatment of hypertension (high blood pressure) in patients on hemodialysis or peritoneal dialysis, and in patients who are renal (kidney) transplant recipients. The prevalence of hypertension is extremely high in end stage renal disease, and is a probable contributor to the epidemic of cardiovascular disease in end stage renal disease (ESRD). However, the lack of prospective, randomized clinical trials makes it difficult to precisely define treatment strategies. The authors conclude that at the present time, the guidelines developed by the National Kidney Foundation's Cardiovascular Disease Task Force should be followed. The Sixth Joint National Committee for Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI) recently lowered their recommended target blood pressures in the general population. JNC VI defined optimal blood pressure in the general population as 120 over 80. Target blood pressure for patients receiving antihypertensive therapy is defined as 140 over 90. JNC VI recommends a target blood pressure of 125 over 75 for patients with chronic renal insufficiency (kidney function less than adequate). The authors note that all classes of antihypertensive drugs, except diuretics, are effective in treating hypertension in ESRD patients. 54 references (21 annotated).

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

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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. •

Permanent Hemodialysis Vascular Access Survival in Children and Adolescents with End-Stage Renal Disease Source: Kidney International. 62(5): 1864-1869. November 2002. Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: Transplantation is the optimal therapy for children with end stage renal disease (ESRD), but in a subset of patients with peritoneal membrane failure, failed transplants, or poor social situations, chronic hemodialysis (HD) remains the only option. Long-term survival of arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) in pediatric patients has not been well described. This article reports on a study of the survival of permanent vascular access in 34 pediatric ESRD patients treated with chronic HD between 1989 and 1995 and followed through 2000. Twenty-four AVFs and AVGs were created in 19 and 23 patients, respectively. Mean age and weight at insertion were 15.1 years (range 7.1 to 20.9 years) and 46 kilograms (18 to 81 kilograms) for AVFs and 13.3 years (3.8 to 21.1 years) and 41.5 kilograms (10.5 to 145 kilograms) for AVGs. Excluding primary failures, 1-year, 3-year, and 5-year patency rates for AVFs and AVGs were not significantly different. Patency did not correlate with patient weight or age at access creation. Primary access failure occurred more often in AVFs (8 of 24) than in AVGs (1 of 28). Access thrombosis (clotting), stenosis (narrowing), and infection occurred more frequently in AVG. The authors conclude that both AVF and AVG function well even in small pediatric patients and have survival rates equivalent to adult series and longer than cuffed venous catheters in pediatric patients. Both AVFs and AVGs are preferable for long-term HD access in pediatrics. 1 figure. 3 tables. 17 references.

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Complications of Chronic Renal Insufficiency: Beyond Cardiovascular Disease Source: American Journal of Kidney Diseases. 36(6, Supplement 3): S31-S38. December 2000. 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: With early recognition and intervention, many of the complications of chronic renal insufficiency (CRI) and its comorbid (other illnesses occurring at the same time) conditions can be eased or prevented. This article reviews the most prevalent, troublesome, and potentially preventable complications and comorbidities of CRI, with a view toward developing high quality, cost effective strategies for delivering early interventional care. Complications of CRI include malnutrition, anemia (low levels of hemoglobin in the blood, resulting in diminished oxygen carrying capacity), disorders of divalent ion metabolism, and osteodystrophy (bone disease), metabolic

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acidosis, and dyslipidemia (dysfunctional amounts of lipids, or fats, in the blood). Important comorbid conditions of CRI are hypertension (high blood pressure), diabetes mellitus, and cardiovascular disease. Clinical intuition suggests that early intervention will avert morbidity related to the hypoalbuminemia and other nutritional disorders of CRI, the metabolic acidosis, and the dyslipidemias, but prospective data are lacking at present. Correction of anemia, usually with recombinant human erythropoietin, may be key to the prevention of cardiac disease and other comorbidities of CRI. Incipient disorders of bone and mineral metabolism are managed prospectively using such measures as protein restriction to reduce phosphorus intake, phosphate binders, calcium supplementation, and vitamin D analogues. Hypertension, whatever its original etiology, is clearly an important risk factor for the progression of kidney failure and for the development of diffuse vascular disease; appropriate and aggressive treatment is essential. In patients with diabetes nephropathy (diabetes associated kidney disease), the principles of both primary and secondary prevention have been validated. The authors conclude by stressing the importance of early intervention to present some of these adverse outcomes of CRI. 2 figures. 3 tables. 60 references.

Federally Funded Research on Chronic Renal Failure The U.S. Government supports a variety of research studies relating to chronic 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 chronic 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 chronic renal failure. The following is typical of the type of information found when searching the CRISP database for chronic 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 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

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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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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: ACUTE STROKE PROTECTION BY ERYTHROPOIETIN AND IGF-I Principal Investigator & Institution: Digicaylioglu, Murat Haydar.; Burnham Institute 10901 N Torrey Pines Rd La Jolla, Ca 920371005 Timing: Fiscal Year 2004; Project Start 15-JUN-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Stroke and the resulting neurological deficits are the most common cause for permanent disability in the United States. The death of neurons by apoptosis and the loss of axons and dendrites play a major role in damage in the penumbra of a stroke and in many neurodegenerative diseases. The aim of the proposed research project is to elucidate the mechanism of a synergistic effect of combinatorial treatment with erythropoietin (EPO) and insulin-like growth factor I (IGF-I) in order to ameliorate the acute and long-term disabilities after stroke. Detailed behavioral studies, including tests of cognitive, locomotor and sensorimotor function, will be conducted in groups of mice. Neurological scores of mice in subgroups subjected to experimental stroke and treated with each cytokine alone will be compared to those administered EPO+IGF-I or vehicle. Neurological benefits of each treatment will be based on the combination of these scores. The occurrence of stroke, indicated by loss of neurons and their extensions in histological sections, and the possible beneficiary effect of EPO?I will be documented by measuring stroke volume. In addition, we will study the signaling pathway triggered by EPO and IGF-I interaction with their respective receptors (EPO-R and IGF-IR) in neurons. We will investigate the cellular mechanisms activated by EPO and IGF-I that protect neurons from apoptosis or axonal/dendritic loss after hypoxiWischemia. HypoxicAschemic injury during stroke causes oxidative and nitrosative stress and produces neuronal damage mediated by increases in glutamate receptor activity and subsequent generation of the free radicals, including nitric oxide (NO) and superoxide (02-). NO and superoxide react to form the neurotoxic product peroxynitrite (ONOO). We show that PI-3 kinase-Akt-1 interaction might be a crucial element in the synergistic effect of EPO and IGF-I. Identification of the neuroprotective signaling pathway(s) for EPO and IGF-I, as proposed in this project, will provide novel

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strategies to ameliorate loss of neuronal function after stroke and provide an impetus to design new combinatorial therapeutic interventions. Our specific aims are: 1. To characterize EPO- and IGF-I-induced activation of PI-3 kinase that contributes to neuroprotection. 2. To investigate the potential role of Akt in EPO and IGF-I activated neuroprotective signaling in vitro. 3. To study the acute treatment of stroke induced by transient middle artery occlusion (TMCAO) in the mouse : with combined application of EPO and IGF-I. EPO is approved to increase red blood cell mass by the U.S. Food and Drug Administration (FDA) for use in patients having chronic renal failure, receiving chemotherapy for cancer, or with antiretroviral drugs for AIDS. IGF-I is currently in advanced clinical trials for other indications. FDA approval for these other indications could expedite the use of EPOAGF-I for the acute treatment of stroke and other neurodegenerative diseases. 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 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

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Project Title: ANABOLIC STEROIDS AND EXERCISE IN HEMODIALYSIS Principal Investigator & Institution: Johansen, Kirsten L.; Assistant Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The federally-funded End Stage Renal Disease program was initiated in 1972 with the goal of extending the lives of individuals with kidney disease and allowing them to return to the work force. Though dialysis has prolonged the lives of patients with ESRD, it has not produced the expected degree of occupational and physical rehabilitation. A recent study showed that more than one third of hemodialysis patients had a Karnofsky score below 70, meaning that they were unable to perform the normal activities of daily living without assistance. Investigation into the causes of this striking debility has been limited, but muscle atrophy and concomitant weakness probably contribute. Reduced lean body mass (LBM) and muscle weakness have been demonstrated in this population. Since muscle strength correlates with performance measures such as gait speed in elderly subjects, the reduction in LBM in dialysis patients may affect functional status, and treatments designed to increase muscle size and strength could be of benefit to such individuals. Both anabolic steroid treatment and resistance exercise training (RE) increase strength and muscle mass in healthy subjects. RE also resulted in improved functional status in frail elderly subjects. While there have been no reports of the effects of RE in patients on dialysis, we recently showed that nandrolone decanoate (ND), a 19-nortestosterone derivative, increased LBM and improved walking and stair-climbing time in patients on dialysis. Furthermore, ND was safe in this population and resulted in only occasional mild side effects. In the current application, we propose to perform two studies concurrently. In one, to elucidate the mechanisms of the muscle defects of dialysis patients, healthy control subjects and patients on dialysis will undergo measurement of physical activity levels, and of muscle size, strength, and oxidative capacity. In the second, we will determine whether RE and/or anabolic steroids can increase muscle size and improve muscle strength and physical performance in patients on hemodialysis. In a 12-week study, 80 hemodialysis patients will be randomly assigned to one of 4 groups as follows: ND, weekly ND injections; EX, resistance exercise training plus placebo injections; ND-EX, ND injections plus RE; and PL, placebo injections only. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

Project Title: ANGIOTENSIN IN DISTAL NEPHRON ONTOGENY Principal Investigator & Institution: Losipiv, Igor V.; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: Congenital kidney malformations are the major cause of chronic renal failure during early childhood and abnormal nephrogenesis is causally linked to the development of adult hypertension. Recent studies have demonstrated that inactivation of the genes encoding components of the renin-angiotensin system (RAS) in mice causes a range of congenital anomalies of the kidney and urinary tract including papillary hypoplasia, hydronephrosis and urinary concentrating defect. This suggests that an intact RAS is required for distal nephron/ureteric bud morphogenesis and function. Accordingly, the primary objective of this proposal is to elucidate the role of the RAS in the ontogeny of the distal nephron. Preliminary results included in this proposal indicate that angiotensinogen, angiotensin II type 1 and type 2 receptors and angiotens in converting enzyme are all expressed in embryonic mouse ureteric bud (UB) cells. This may explain why RAS inactivation leads to abnormal development of the renal medulla. We hypothesize that the developing distal nephron expresses a functional RAS that regulates branching morphogenesis and/or tubulogenesis. This hypothesis will be tested in 3 specific aims. Specific Aim 1 is to demonstrate that the developing distal nephron expresses all the components of the RAS. Specific Aim 2 is to characterize the effects of angiotensin II on ureteric bud branching and tubulogenesis in vitro. Specific Aim 3 is to determine the intracellular signaling pathways and secreted molecules that mediate angiotensin II-induced tubulogenesis. The proposed studies will open new avenues in RAS research as related to kidney development and the results may lead to potentially new intervention strategies for the prevention and treatment of congenital renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: APOPTOSIS IN TUBULAR ATROPHY OF PROGRESSIVE RENAL FAILURE Principal Investigator & Institution: Schelling, Jeffrey R.; Associate Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: Chronic renal failure is initiated primarily by glomerular injury, but tubular atrophy is a better predictor of renal disease progression, despite its prognostic importance, tubular atrophy is only a description for the absence of renal tubular epithelial cells (RTC) and the molecular mechanisms underlying RTC deletion are unknown. Based upon preliminary data which demonstrates that Fas expression is increased in RTC in chronic renal failure, the overall goal of this proposal is to determine whether hypoxia induces Fas-dependent RTC apoptosis. The hypothesis which will guide these experiments is that in chronic renal failure, hypoxia promotes RTC apoptosis through induction of RTC Fas expression. Furthermore, ligation of RTC Fas ligand with up-regulated Fas on adjacent target RTC induces lymphocyteindependent, fratricidal apoptosis via activation on signaling pathways that include down-regulation of bcl-2 and/or stimulation of bcl-2 phosphorylation. The goals of this project will be approached with the following specific aims: 1. To test whether hypoxia promotes RTC apoptosis through Fas induction, the effects of hypoxia on Fas function and apoptosis will be investigated. 2. To test for Fas-dependent fratricidal apoptosis, the RTC Fas-RTC Fas ligand interaction will be characterized. 3. To test whether Fas induction contributes to the chronic renal disease phenotype, in vivo and in vitro studies will be conducted to inhibit Fas activation. Upon completion of the proposed studies, we expect to provide a better understanding of the mechanisms which regulate tubular atrophy, thereby forming a basis for the design of therapeutic strategies to inhibit tubular atrophy and the progression of chronic renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 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

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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: BIOMEMS MATERIALS FOR RENAL TISSUE ENGINEERING Principal Investigator & Institution: Fissell, William H.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): End-stage renal disease (ESRD) affects 378,000 Americans and is increasing in prevalence at 8% / year. Of the three treatment options (transplant, peritoneal, and hemo dialysis) none is ideal, as transplant is severely limited by scarcity of donor organs and both dialytic modalities are expensive and confer significant morbidity and mortality. Advances in the treatment of ESRD will involve the tissue engineering of nephronal units; indeed, a tissue-engineered renal tubule cell device is presently in clinical trials. For this technology to be generally applicable, devices must be compact, inexpensive, and self-monitoring. An eventual goal of this line of research is an implantable tissue engineered device for renal replacement therapy. The advent of Microelectromechanical Systems (MEMS) technology has produced practical surface and bulk micromachining techniques with the ability to manufacture mechanical devices (pores, valves, gears etc.) with feature sizes on the same order of magnitude as subcellular organelles, in combination with on-chip electronics and sensors. This combination allows MEMS devices to sense their local environment and intelligently act upon the local environment by changing electrical and mechanical properties of the devices. Preliminary testing of a MEMS ultrafilter for use in renal replacement therapy has begun, as well as definition of the biocompatibilty of MEMS materials. This project seeks to demonstrate attachment and stable growth of renal proximal tubule cells (RPTCs) on silicon and other MEMS materials. Specific Aim 1: Demonstrate attachment of porcine and human RPTCs to mono- and poly-crystalline silicon, silicon dioxide, silicon nitride, and polydimethoxysilane ("MEMS materials"), with and without extracellular matrix proteins. Specific Aim 2: demonstrate the RPTCs on MEMS materials are able to form stable monolayers with tight junctions. Specific Aim 3: demonstrate metabolic activity, includingammoniagenesis, Vitamin D hydroxylation, and glutathione metabolism by RPTCs on MEMS materials. Specific Aim 4: Demonstrate attachment, growth, and differentiated function of RPTCs on nanoporous substrates. This project has a high likelihood of success, and provides a necessary first step in the tissue engineering of an implantable nephronal unit. Failure of

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Chronic Renal Failure

RPTCs to grow on these substrates despite a variety of suface modifications would be extremely important, as it would indicate a need for new materials in bioengineering. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CA2+ HYPERPARATHYROIDISM

SENSING

RECEPTOR

EXPRESSION

IN

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 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: CARDIAC AND RENAL DISEASE STUDY (CARDS) Principal Investigator & Institution: Iribarren, Carlos; Physician / Scientist; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004

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Summary: (provided by applicant): Mild-to-moderate chronic renal insufficiency (CRI) is reaching epidemic proportions in the US. Studies relating mild-to-moderate CRI and cardiovascular risk are limited and inconsistent. Although we have learned much about the natural history and adverse outcomes associated with end-stage renal disease (ESRD), we have little specific information regarding risk factors for the development or progression of renal disease. Using a population-based, ethnically diverse large cohort of male and female health plan enrollees with extended follow-up, we propose: Aim 1: To evaluate: a) whether baseline and decline in renal function overtime are independent predictors of coronary heart disease (CHID), stroke, heart failure and peripheral vascular disease; b) effect modifiers of these relationships, including baseline hypertension and diabetes status. Aim 2: To determine whether baseline and increase over time in blood pressure level (as well as prevalent and incident hypertension) are predictive of the subsequent risk of ESRD after adjusting for diabetes and for baseline serum creatinine, proteinuria and hematuria. Aim 3: To examine other potential predictors of ESRD including demographic factors (race/ethnicity, level of education) total cholesterol level, family history of renal disease, body mass index, sagittal abdominal diameter, cigarette (as well as cigar and pipe) smoking, coffee intake, alcohol consumption, family history of renal disease and self-reported occupational exposures. We will take advantage of existing longitudinal data resources at the Northern California Kaiser Permanente Division of Research and available patient-level crosslinkage with the US Renal Data System end-stage renal disease registry to obtain comprehensive renal and cardiovascular outcomes. A de novo prospective study of this magnitude and duration will be prohibitively expensive and time-consuming. This proposal will leverage unique resources and methodological expertise to provide novel insights into the epidemiology of renal disease and its association with cardiovascular events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIAC OSTEODYSTROPHY

OUTCOMES

ASSOCIATED

WITH

RENAL

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 Sets (CHIPS) database. The serum markers of interest are intact PTH, calcium, and

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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: CARDIOVASCULAR INSUFFICIENCY

RISK

FACTORS--CHRONIC

RENAL

Principal Investigator & Institution: Sarnak, Mark J.; Assistant Professor of Medicine; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Chronic renal disease is a major public health problem in the US. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality. Prevention of CVD in chronic renal disease requires early intervention, during the stage of chronic renal insufficiency (CRI). The general hypothesis for the proposed research program is that the progression of CVD and chronic renal disease share common mechanisms; and that "traditional" and "uremia-related" risk factors, in particular total plasma homocysteine (tHcy), lipoprotein(a) (Lp(a)) and C-reactive protein (CRP), contribute to the progression of both CVD and chronic renal disease. 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 cardiovascular epidemiology in chronic renal disease. He will obtain a Master's of Science in Clinical Care Research, participate in projects utilizing a broad range of study designs for clinical care research, and carry out an original research project from its inception to completion. His mentors have extensive experience in clinical investigation in nephrology, CVD epidemiology and clinical care research methodology. There are currently minimal data available on the incidence of CVD or the risk factors for CVD in CRI. The Modification of Diet in Renal Disease (MDRD) Study was the largest prospective study of patients with CRI, and is an ideal study population for the proposed research. Specific aims are as follows: 1. Measure tHcy, Lp(a), apo(a) isoforms and CRP levels from frozen samples taken at baseline in the MDRD Study and characterize the distribution of levels and their relationship to baseline glomerular filtration rate (GFR) and other factors. 2. Determine whether baseline levels of tHcy, Lp(a), apo(a) isoforms or CRP are predictors of subsequent GFR decline. 3. Resume contact with the MDRD Study cohort, collect data on CVD and renal outcomes, and determine the relationship of traditional and uremia-related risk factors to CVD and renal outcomes. Statistical analysis reveals adequate power to evaluate each aim and a pilot study has documented the feasibility of aim 3. The PI has assembled a team of nephrologists, CVD epidemiologists, and nutrition scientists to assist him in the conduct of the project; enlisted the collaboration of the MDRD Study Data Coordinating Center, and organized internal and external advisory committees to monitor his progress. The proposed L 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

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Project Title: CHRONIC RENAL INSUFFICIENCY IN NAPRTCS PATIENTS Principal Investigator & Institution: Warady, Bradley; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This application, a joint effort of 26 centers of the NAPRTCS, is entitled "Chronic Renal Insufficiency (CRI) in NAPRTCS Patients. We will enroll 300 children (1-16 years) with measured glomerular filtration rates (GFR) of 25-75 mL/min/1.73m2. Follow-up with annual GFR and 6 month physical examinations and determinations of hemoglobin, electrolytes, serum, albumin, serum calcium, serum phosphorus, parathyroid hormone and urinary indices will test the 1st hypothesis that this cohort will most accurately define the rate of and the risk factors for progression of CRI, and that this progression will be correlated with proteinuria, albumin, blood pressure, nutritional status, growth and hyperparathyroidism. To test the 2nd hypothesis that cardiovascular disease develops in children with mild CRI and that its prevalence and severity increase in association with the progression of CRI, we will perform baseline and annual 24-hour ambulatory blood pressure monitoring, echocardiographic assessments to determine left-ventricular mass and LV function, and B-mode ultrasound of the carotid artery to determine the IMT and carotid artery compliance. To test the 3rd hypothesis that the neurocognitive outcome of children with CRI is influenced by the progression of renal insufficiency, a battery of validated neurocognitive tests will be conducted at study entry and at 6, 12 and 24 months to assess many cortical and subcortical areas of brain function. To test the 4th hypothesis that chronic inflammation contributes to cachexia, growth hormone resistance and growth retardation, we will examine the impact of circulating cytokine and neuropeptide concentrations on dietary intake, nutritional and growth parameters as well as growth hormone axis pertubations and responsiveness to growth hormone therapy. Finally, to test the 5th hypothesis that a correlation exist between bone histology, serum concentration of PTH and measured GFR, we will measure and characterize the biochemical and histologic features of renal osteodystrophy and determine the serum concentrations of PTH that are associated with normal rates of bone formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL OUTCOME OF HEMODIALYSIS IN UTAH Principal Investigator & Institution: Cheung, Alfred K.; Professor of Medicine; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2004 Summary: The mortality rate of U.S. chronic hemodialysis patients is higher than that in other industrialized nations. Available data suggest that this high mortality rate is partially a result of inadequate delivery of dialysis. The MMHD is a prospective, randomized, multicenter, two-by-two factorial trial sponsored by NIDDK to determine if increasing the amount of delivered dialysis (as assessed by a two-pool, variablevolume urea kinetic model) and using high flux biocompatible dialysis membranes would improve the clinical outcome of these patients. This application describes the University of Utah Dialysis Program (together with the Salt Lake City VA Medical Center dialysis unit) and proposes that this Program participates as a Clinical Center in the MMHD Full Scale Study. The University of Utah Dialysis Program consists of 7 dialysis units, some of which are located in suburban communities, that have common administrative and medical guidelines originating from the University headquarters.

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The VA-unit is also closely affiliated and has similar protocols. The investigators in this proposal have significant expertise in their respective areas. Both the institution and the investigators have a long tradition in laboratory and clinical dialysis research. They have recently performed several clinical studies involving patients from the different dialysis units within the Program. The P.I. has also participated in several multicenter clinical trials with centers outside Utah. The ESRD population in this Program has been growing. The number of in-center hemodialysis patients, as of December 31, 1993, was 237, of which 37% were diabetic. The majority of these patients are Caucasian (78%), but there is a significant fraction (5%) of Native Americans. This Program will recruit approximately 108 patients during the first 18 months of the Study and randomly allocate 60 of them to 4 hemodialysis treatment strategies that differ in the amount of delivered dialysis and/or the type of dialysis membrane. Sixty patients will be maintained throughout the study by using a "recruit to replace" strategy. Many of the medical and technical aspects of therapy, including nutritional intake, will be standardized during the baseline and a 60 month follow-up period. The primary outcome is death of the patient; secondary outcomes include non-access related hospitalization, hospitalization for heart disease or infection, and declining serum album in. The results from this trial will guide hemodialysis therapy in the future. 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.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE CLINICAL TRIALS IN VASCULAR ACCESS Principal Investigator & Institution: Dixon, Bradley S.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: The Eastern Iowa Western Illinois Vascular Access Consortium (EIWIVAC) is a consortium of hemodialysis units surrounding the University of Iowa co-founded by a vascular biologist and an expert in clinical trials design to address the problem of vascular access failure. Hemodialysis vascular access failure is a frequent cause of morbidity and a major expense in caring for hemodialysis patients. The cause of access failure is neointimal hyperplasia leading to stenosis and thrombosis. This process occurs in both arteriovenous grafts (AVG) and native fistulas (AVF). The hypothesis underlying the present proposal is that pharmacological agents that inhibit vascular smooth muscle cell (vsmc) proliferation will decrease the neointimal hyperplasia and prolong vascular access survival. Both HMG CoA reductase inhibitors and dipyridamole have been shown to inhibit vascular smooth muscle cell proliferation. HMG CoA reductase inhibitors prevent the isoprenylation of small GTP binding proteins such as Ras that are needed for cell proliferation. Dipyridamole increases extracellular adenosine levels that can inhibit proliferation by unclear mechanisms. Studies from our lab have shown that combined treatment with these agents in low doses is additive or even synergistic at inhibiting vsmc proliferation. Therefore, we propose a randomized placebo controlled primary prevention trial using a factorial design to test whether treatment with either dipyridamole or an HMG CoA reductase inhibitor will increase primary survival of a newly created vascular access: either an AVG or an AVF. In addition, we briefly propose two additional trials. With access monitoring to detect stenosis before access failure, many prevalent accesses will require angioplasty. However, the restenosis rate after angioplasty is very high and resistant to many pharmacological agents. We propose in a second trial to test the hypothesis that the more potent antiproliferative effects of rapamycin in combination with an HMG CoA reductase inhibitor will inhibit the smooth muscle cell proliferation leading to restenosis. Finally, data shows that an upper arm native fistula (UAF) has superior survival to an AVG. However, the UAF appears to be underutilized in part because of concerns over high access flow rates and the possibility of increased heart failure and distal steal syndromes. While a randomized trial is not possible, we propose to establish a registry to examine the safety of a UAF compared to an AVG. If safety issues can be addressed, increased utilization of UAF may be the most cost-effective intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--RENAL-KIDNEY DISEASE RESEARCH Principal Investigator & Institution: Fink, Jeffrey C.; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: The aims of the Renal Research Core are: Specific Aim 1: Merge the complementary elements of the UMSHN and ERI program at UMB to enhance the primary missions of each entity and develop a unified action plan within the Kidney Disease Research Core. Specific Aim 2: Utilize the structure of the UMSHN and the focus of the ERI Program to increase surveillance for early kidney disease particularly in areas of underserved populations with a high predominance of African-Americans.

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Specific Aim 3: Set up pathways through which individuals with kidney disease identified from the statewide surveillance program can link into ongoing studies, educational initiatives and specialized care programs that are all dedicated to narrowing the racial disparity in kidney disease Specific Aim 4: The Renal/Kidney Disease Research Core will establish an effective and enduring infrastructure for sample and data collection that can be utilized for community-based enrollment and examination of individuals participating in ongoing and future trials related to kidney disease. The Renal/Kidney Core also has the outstanding participation of Dr. Eve Higginbotham as a Co Investigator. Dr. Higginbotham will participate in the Renal/Kidney Research Core as well as the Shared Resource Core. In the Renal/Kidney Research Core, she will lend her expertise in the area of ophthalmologic disorders, which affect patients at risk for renal disease, patients with renal disease, such as diabetics and hypertensives, or renal patients who have comorbidity such as glaucoma. Dr. Higginbotham and her faculty and staff, Drs. Scott Steidl and Nancy Ellish, will evaluate, in the Shared Resource Core, a novel Teleopthalmology project that may assist renal patients and other types of patients with compliance with recommended guidelines for eye screening. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORONARY CALCIFICATION IN HEMODIALYSIS PATIENTS Principal Investigator & Institution: Goodman, William G.; Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 29-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Cardiovascular disease accounts for half the deaths in adults undergoing regular dialysis, but the mechanisms responsible remain uncertain. Recent evidence indicates, however, that certain disturbances in mineral metabolism, and/or the therapeutic measures aimed at controlling them, contribute to the development of coronary artery and vascular calcification in patients treated with longterm hemodialysis. Coronary calcification is common in those with end-stage renal disease (ESRD), and the disturbance may account, at least in part, for the high mortality rate from cardiovascular causes in this population. The multi-center, randomized, clinical trial outlined in the current proposal is designed to assess the roles of two separate, yet potentially related, determinants of coronary artery calcification in patients with ESRD who are treated with hemodialysis. The impact of reducing the amount of calcium given orally to patients with ESRD by using sevelamer (RenaGel) rather than calcium-based compounds to control serum phosphorus will be evaluated. Coronary artery calcification will be measured by electron beam computed tomography (EBCT) before and after 12 months of treatment. In addition, the effect of lowering serum total and LDL cholesterol levels on coronary artery calcification scores will be assessed during treatment with either simvastatin or placebo to inhibit 3-hydroxyl-3methylglutaryl Co-enzyme A reductase (HMG Co-A). Potential interactions between these two therapeutic interventions on coronary artery calcification scores will be examined using a 2 x 2 factorial study design. The primary outcome variable is the coronary artery calcification score after 12 months of treatment in each of four groups. The broad objectives of the project are to determine the efficacy of two therapeutic interventions aimed at modifying factors thought to contribute to the development and progression of coronary artery calcification, and possibly to cardiovascular mortality, in patients undergoing long-term dialysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIALYSIS FACILITY MANAGEMENT Principal Investigator & Institution: Eisenstein, Eric L.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 31-AUG-2004 Summary: Taken by Applicant): Medicare's End-Stage Renal Disease (ESRD) program is the only public program that provides health insurance coverage for a specific disease. ESRD patients typically survive fewer than five years after beginning renal dialysis. During this time they average 1.9 hospitalizations per year, for a total of 14 days. Previous studies have reported significant variations in a dialysis facility management practices, treatment costs and profitability. However, little is known about the relationships between dialysis facility characteristics and long-term dialysis patients' clinical and economic outcomes. We hypothesize that dialysis facility characteristics primarily influence total medical costs by modifying dialysis patient hospital events (frequency and type). Additionally, we hypothesize that changes in dialysis facility management practices may improve long-term clinical outcomes for dialysis patients and for the ESRD system as a whole. However, these changes may also increase dialysis facility operational costs. Using information from three consecutive years of incident dialysis patients with a minimum of one and a maximum of three years follow up on all patients, this project will evaluate these hypotheses. Follow-up will begin on the 91 days after dialysis initiation and continue until death or renal transplantation. After adjusting for differences in patient clinical characteristics, we will define the impact of dialysis facility characteristics on dialysis patients: (1) mortality (survival and life expectancy), (2) morbidity (hospitalization rates and event-free survival, death, or hospitalization) and (3) total medical costs (dialysis treatment, hospitalization, physician and supplies). We will then assess the economic attractiveness (cost-effectiveness or cost-savings) of dialysis facility management practices that improve dialysis patient long-term clinical outcomes and develop decision models for the dissemination of study results. Through these aides, dialysis patients, providers, payers and policy maker will be able to: determine how dialysis facility management practices impact long-term clinical and economic outcomes and identify optimal management practices to improve survival or decrease total medical costs for dialysis patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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Chronic Renal Failure

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 •

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 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

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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 RENAL INSUFFICIENCY ON CARDIOVASCULAR OUTCOMES Principal Investigator & Institution: Schwab, Steve J.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2004 Summary: (Verbatim from the application): Cardiovascular disease accounts for almost half of the reported deaths for patients receiving maintenance dialysis. Because incident dialysis patients often have advanced coronary artery disease that is less amenable to treatment as compared with patients with normal renal function, the greatest impact of therapy will be obtained through invention among patients with renal insufficiency, prior to their development of ESRD and earlier in the development of the coronary artery lesions. This proposal will define the impact of varying degrees of chronic renal insufficiency on five-year survival among patients with significant coronary artery disease. This study will further compare patient survival following treatment for coronary artery disease (medical, percutaneous coronary artery intervention and coronary artery bypass grafting) among patients with mild, moderate, and severe renal insufficiency. After evaluating these clinical outcomes, this proposal will estimate the cumulative five-year medical resource utilization (rehospitalizations and cardiac procedures) and costs for patients with chronic renal insufficiency and significant coronary artery disease to compare costs among major patient subgroups. A retrospective cohort design will be used to take advantage of the Duke Databank for Cardiovascular Diseases (DDCD), a large, comprehensive patient database, maintained by the Duke Clinical Research Institute (DCRI) and its associated hospital and physician administrative databases. This study will examine the cardiovascular outcomes that affect the survival of patients with chronic renal insufficiency and patients receiving chronic dialysis. The results of this study will provide evidence for early intervention among the pre-ESRD population with chronic renal insufficiency to improve maximize the efficacy of coronary revascularization and improve survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: END OF LIFE PREFERENCES & OUTCOMES: PATIENTS & SPOUSES Principal Investigator & Institution: Pruchno, Rachel A.; Director; None; Boston College 140 Commonwealth Ave Newton, Ma 02467 Timing: Fiscal Year 2002; Project Start 05-SEP-2000; Project End 31-MAY-2005 Summary: Proposed is a prospective longitudinal study of: (1) the end of life preferences for treatment held by patients with chronic illness and their spouses; (2) the ways that end of life preference of patients and spouses change over the course of a chronic illness;

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and (3) the effects that end of life preferences and actual administration of various end of life treatments have on the sense of burden, grief, and mental health of the patient's spouse. The overall goal of the study is to gain better understanding of the preferences for end of life treatment and the effects of such preferences within the contexts of both the marital dyad and the course of chronic disease. Grounded in family stress theory, the central hypotheses to be tested are: (1) Patient and spouse preferences for end of life treatment vary directly as a function of perceptions of quality of patient life and indirectly as a function of the stressors (e.g., physical health and functional ability of the patient) and resources (religious/spiritual, marital relationship, social support) of patients and their spouses; (2) The greater the congruence between patient and spouse regarding end of life preferences, the less the sense of burden the spouse will feel. Reduced burden, in turn, results in better mental health for the spouse; (3) Over the course of disease, as quality of life declines, preferences for treatment will change from those focused on aggressive treatment to those that are more palliative; (4) The greater the degree of spouse congruence regarding preferences for end of life treatment and the greater the extent of congruence between preferences for treatment and actual end of life treatment administered, the less grief will be experienced by the spouse after the death of the patient and the better will be the mental health of the spouse. In order to address these hypotheses, a five-year prospective longitudinal study design is proposed. 325 patients with ESRD and their spouses would be assessed comprehensively at baseline and then briefly at four times (9, 18, 27, 36 months) over the course of the three years. Spouses who become widowed during the observation period would participate in a single post-death interview. Analyses would focus on both cross-sectional and prospective longitudinal relationships using a combination of a regression, structural equation modeling, and categorical data analysis techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF DEMENTIA IN OLDER DIALYSIS PATIENTS Principal Investigator & Institution: Murray, Anne M.; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, Mn 55404 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Candidate: Anne Murray, M.D., M.Sc., is a fellowship-trained geriatrician with a Masters in Epidemiology and a staff physician at Hennepin County Medical Center, a teaching hospital affiliated with the University of Minnesota. She is also an investigator with Nephrology Analytical Services, an epidemiology laboratory and repository for the NIH's United States Renal Data System (USRDS) database. Dr. Murray's immediate goal is to pursue research in the epidemiology and prevention of cognitive impairment in dialysis patients. Career Objectives: Dr. Murray's immediate career objectives include: 1) advanced coursework in neuropsychology, study design, longitudinal analysis, and ethical conduct of research, 2) work with her mentors to further develop her research skills in the area of cognitive impairment in renal disease through regularly scheduled meetings and directed readings, 3) conduct a three-year longitudinal study of the prevalence and progression of cognitive impairment in dialysis patients under the guidance of her mentors, 4) continue to conduct analyses on the epidemiology of dementia in dialysis patients using the USRDS database, and 5) during the last year of the award, develop a proposal to obtain funding for a prospective study of the incidence of and risk factors for cognitive impairment in patients with chronic kidney disease, formerly called chronic renal insufficiency. Dr. Murray's long-term career objective is to attain independence as an investigator in the area of epidemiology of cognitive impairment in

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renal disease and other chronic diseases. Research Plan: During the five-year award period, Dr. Murray plans to use findings from analyses of her pilot data and the USRDS database to conduct a prospective longitudinal study of the prevalence and progression of cognitive impairment in dialysis patients in the Twin Cities. The study will test the hypotheses that 1) dialysis patients have a higher prevalence of cognitive impairment than the general population, 2) the risk of cognitive impairment increases with duration in years of dialysis, and 3) age, Modified Mini-Mental State Examination (3MS) score at baseline, education, and history of stroke will be strong predictors of the rate of progression of cognitive impairment in dialysis patients. Subsequently, Dr. Murray plans to collaborate with her mentors to write a major proposal to examine the epidemiology of cognitive impairment in patients with chronic kidney disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXTRA-RENAL REGULATION OF POTASSIUM HOMEOSTASIS Principal Investigator & Institution: Mcdonough, Alicia A.; Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): Extracellular fluid (ECF) +} must be maintained within a narrow range. If ECF +] falls too low (hypokalemia), cell membranes hyperpolarize, and if ECF +] increases too much (hyperkalemia) cell membranes depobrize, both disrupt normal electrical excitability and can have life threatening cardiac effects. Kidneys and muscle work in concert to maintain ECF ]. During hypokalemia muscle ICF K is redistributed to buffer the fall in ECF }. During hyperkalemia K+ is pumped into muscle ICF until renal adjustments can occur. These important muscle specific homeostatic processes are only beginning to be understood at the molecular level. Evidence supports the hypothesis that K loss from muscle during hypokalemia results from decreased active K+ influx mediated by sodium pump (Na,KATPase, NKA) inhibition, and that K+ uptake during hyperktilemia is mediated by sodium pump activation. Our lab has established that during low K+ diet abundance of NKA subunits are depressed in an isoform and muscle specific manner: 60-95 percent fall in a2, not a 1. Using a novel K+ clamp technique, we recently showed that early in K+ restriction, prior to fall in a2, there is a severe blunting of both insulin stimulated K+ uptake, and of insulin stimulated redistribution of NKA ct2 type pumps from endosomes to the plasma membrane (PM). Evidence is mounting that the bumetanide sensitive Na,K,2C1 cotransporter also accounts for a component of muscle K+ influx and, thus, could play a role in potassium homeostasis. The overall aims are to determine the molecular mechanisms responsible for tapping muscle K+ stores during hypokalemia, for clearing excess plasma +] into the ICF store after K+ restoration, and to understand how these processes are altered in a set of clinically relevant paradigms. The contribution of both Na,K-ATPase isoforms and NKCCI in both red oxidative white glycolytic muscle will be studied with a compartmental analysis approach in which the following are assessed: whole body K+ uptake, muscle specific K+ transport, subcellular distribution and activity of K+ transporters, and pool size regulation of K transporter protein and mRNA levels. Aim 1 will test the hypothesis that the shift of K+ to ECF during K restriction is mediated by decreased plasma membrane (PM) expression of both NKA a2 and NKCC1 coupled to resistance to insulin stimulated K+ uptake, and that this process is altered in uremia accompanying chronic renal failure. Aim 2 will test the hypothesis that thyroid hormone or dexamethasone, both of which increase NKA cx2 (and perhaps NKCC 1), alter extrarenal control of K+ horneostasis. Aim 3 will

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Chronic Renal Failure

test the hypothesis that the uptake of K+ from ECF to ICF during K+ restoration (following K+ restriction) is mediated by normalizing surface expression of both NKA a2 and NKCC1. Accomplishing these aims will identify the cellular mechanisms responsible for tapping and repleting the muscle K+ reservoir, which will, ideally, suggest strategies to manipulate muscle K stores in clinical settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FREQUENT HEMODIALYSIS CLINICAL TRIALS: NOCTURNAL Principal Investigator & Institution: Rocco, Michael V.; Professor of Medicine; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Wake Forest University has established a clinical consortium to provide six times per week nocturnal home hemodialysis for the NIH RFA for Frequent Hemodialysis Clinical Trials. This consortium consists of ten clinical sites located in the eastern United States, eastern Canada and the Midwestern United States. The consortium includes four of the largest nocturnal home hemodialysis programs in the United States, located in Lynchburg, VA, Saratoga Springs, NY, New York City, NY and Kansas City, MO and one of the largest nocturnal home hemodialysis programs in Canada at London, Ontario. Our clinical centers have more than 190 patient-years of experience with nocturnal home hemodialysis and have provided more than 60,000 home nocturnal hemodialysis treatments. The one year mortality rate for patients receiving nocturnal home hemodialysis at these centers is 4.7% (based on 84.9 patient-years of follow-up), significantly less than the 16.6% mortality rate observed in the NIH sponsored HEMO Study. The observed one year mortality rate for this cohort was 4, compared to an expected mortality rate of 15.8 (chi-square = 8.8, p < 0.005). This consortium proposes to randomize chronic end stage renal disease patients to either six times per week nocturnal home hemodialysis or standard three times per week hemodialysis. Patients will be assessed for the suitability of nocturnal home hemodialysis via a standardized protocol during the baseline period. Those patients that are found to be suitable will then be randomized. Patients will be followed for 12 to 18 months. The primary goals of this study will be to determine the feasibility of randomizing patients into this trial. The primary outcome for the study will be all-cause hospitalizations. Secondary outcomes will include mortality, protein and energy intake, anthropometrics, quality of life, functional status and physical activity. Laboratory data, dialysis parameters and patient medications will also be collected to assess the impact of the interventions on hypertension, anemia, and secondary hyperparathyroidism and electrolyte abnormalities. All hospitalizations, including inpatient and outpatient access interventions, will also be tracked. Direct cost estimates of the two different hemodialysis treatments from a limited societal perspective will also be obtained. Patient safety will be monitored by an external Data Safety and Monitoring Board. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL CHARACTERIZATION OF THE GENE NPHP4 Principal Investigator & Institution: Hildebrandt, Friedhelm; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY-2008 Summary: (provided by applicant): Functional characterization of the gene (NPHP4) causing nephronophthisis type 4. Nephronophthisis (NPHP), an autosomal-recessive

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cystic kidney disease, constitutes the most frequent genetic cause of chronic renal failure in the first two decades of life. Histologically, the disease is characterized by disrupted tubular basement membrane structure, renal tubular cell atrophy, interstitial fibrosis and cyst formation. In a subset of patients with NPHP there is an association with retinitis pigrnentosa, known as Senior-Loken syndrome (SLS). We have previously identified by positional cloning the gene (NPHP1) for juvenile nephronophthisis. Its gene product "nephrocystin" interacts with signaling proteins that regulate actin organization in the cytoskeleton. We have also identified by positional cloning the gene (NPHP3), mutations in which cause NPHP type 3 and the mouse renal cystic phenotype pcy. In addition, using a candidate approach, we have identified mutations in the human inversin gene as causing NPHP type 2 and demonstrated its expression in primary cilia of renal tubule cells, thus linking the pathogenesis of NPHP to disease mechanisms of polycystic kidney disease. Recently, we have identified by positional cloning the gene (NPHP4) causing NPHP type 4 and SLS type 4. NPHP4 is unique to human and mouse genomes and encodes a novel protein, nephroretinin, which is conserved in the nematode C. elegans. We generated first functional data by demonstrating that, i) nephroretinin is expressed in primary cilia of renal epithelial cells, ii) nephroretinin localizes to specific cUiated neurons in C. elegans which express other proteins relevant for renal cystic disease, and iii), NPHP4 mutations exhibit oligogenic inheritance with other NPHP genes. This proposal is aimed at the functional characterization of the novel NPHP4 gene product "nephroretinin" that we identified. Specifically, we propose to: 1) Determine how oligogenic mutations in nephronophthisis genes influence genotype/phenotype relationships; 2) Characterize the function of the NPHP4 gene and its role in the pathogenesis of NPHP type 4; 3) Generate and characterize mouse models of targeted disruption of the Nphp4 and Nphpl genes. Since nephroretinin represents a novel gene product, we expect these studies to provide new insights into disease mechanisms of renal interstitial fibrosis and cyst development in developing and adult kidney and into the function of the retina. 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,

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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 •

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 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

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Project Title: GENE THERAPY TREATMENT FOR SEVERE ANEMIA Principal Investigator & Institution: Lewis, David L.; Senior Scientist; Mirus Corporation 505 S Rosa Rd, #104 Madison, Wi 53711 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 30-SEP-2002 Summary: (provided by the applicant): Gene therapy holds a promise for the treatment of both acquired and genetic diseases. Patients with diseases including end-stage kidney disease, acquired immunodeficiency syndrome and patients who are treated for cancer with high dose chemotherapy and bone marrow transplantation often develop anemia that can be treated or prevented by injection of recombinant EPO protein. EPO delivery via gene therapy would provide a significant treatment benefit. EPO is normally expressed in the kidney, which is a poor target for gene therapy in most patients because of severe organ failure. Yet, serum proteins such as EPO can be produced at ectopic sites and secreted to the serum. A novel method of intra-vascular injection of plasmid DNA expression vector results in highly efficient tranfection of skeletal muscle. This project will use this simple and innovative approach to develop a gene therapy protocol for the treatment of severe anemia. In this Phase 1 application, experiments are proposed to optimize EPO expression following intra-vascular delivery of plasmid DNA expression vectors and test this gene therapy protocol in a severe anemia model. During the Phase II studies, intra-vascular delivery techniques will be optimized to target small, defined muscle groups in a safe clinically applicable protocol. PROPOSED COMMERCIAL APPLICATION: The intravascular delivery methodology will be used in Phase III for the internal development of gene therapy protocols for severe anemia and applications such as clotting factor abnormalities, phenylketonuria, a1-antitrypsin deficiency, complement factor deficiencies, and other hematologic or metabolic disorders within Mirus and licensed to other companies for use within their ene therapy applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AMERICANS

GENETICS

OF

DIABETIC

NEPHROPATHY

IN

MEXICAN

Principal Investigator & Institution: Abboud, Hanna E.; Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The prevalence of type 2 diabetes in Mexican Americans, a large minority ground in the United States, is two to three times higher than in Caucasians. The prevalence of end-stage renal disease (ESRD) in Mexican Americans with type 2 diabetes is almost 3-4 times higher than in Caucasians. The pathogenesis of diabetic nephropathy (DN) is not well understood but circumstantial evidence indicates the existence of a genetic basis for this disease. This grant application is a response to the RFA "Diabetic and Non- Diabetic Nephropathy Susceptibility Genes" (DK-99-005), and proposes to establish a Participating Investigation Center (PIC) at the University of Texas Health Science Center at San Antonio. As a family ascertainment center, the San Antonio PIC has the goal to ascertain approximately extended, multiplex families through ESRD patients recruited at dialysis and transplant clinics in San Antonio and South West Texas. In addition, this center will develop a quality control procedure for the family ascertainment. Questionnaires developed for this procedure will be available to all PICs. San Antonio is an 3excellent location to recruit and enroll Mexican American participants for genetic studies. Approximately 60% of inhabitants in San Antonio and South West Texas are Mexican Americans. More than half of the 5,700 ESRD patients in

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San Antonio and South West Texas are expected to be Mexican Americans. Therefore, the study population will be large enough to recruit the proposed set of 150 families. The San Antonio PIC proposes to perform three local research projects. (1) Phenotyping the set of families investigated in The San Antonio Family Diabetes Study (SAFADS, PI: Dr. M. Stern) for DN us under way. These families have already been genotyped with over 400 markers. We plan to have performed a variance component analysis (VCA) for the SAFADS families to identify possible candidate regions for DN genes by the end of the first year of funding. (2) Based on these early linkage results, a candidate region/gene analysis will be performed with the newly identified "ESRD pedigrees" applying VCA. (3) We will conduct a medical anthropological study to investigate how ESRD patients and their "healthy" relatives experience type 2 diabetes and DN when these diseases cluster in families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 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

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Project Title: HGF GENE THERAPY FOR CHRONIC RENAL FIBROSIS Principal Investigator & Institution: Liu, Youhua; Associate Professor; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (Provided by applicant): End-stage renal disease (ESRD) is one of the most devastating diseases with great morbidity and mortality, and the number of patients is on the rise worldwide. Despite diverse primary etiologies, the pathogenesis of chronic renal diseases progressing to ESRD is a remarkably monotonous process characterized by relentless accumulation of extracellular matrix (ECM) leading to widespread tissue fibrosis. Thus, developing a scheme to inhibit fibrosis appears to be a key strategy for the treatment of chronic renal disease. Preliminary studies in our laboratory suggest that hepatocyte growth factor (HGF) is an important regulator of extracellular matrix turnover leading to inhibition of tissue fibrosis in animal model of renal diseases. Because exogenous HGF is very unstable in blood circulation due to the rapid clearance by liver, we recently develop a gene transfer strategy using naked plasmid vector resulting in efficient expression of HGF protein in vivo. Based on these results, we hypothesize that delivery of HGF gene is an effective therapeutic strategy for the treatment of chronic renal disease. In this application, we propose to administrate HGF gene into animal model of progressive renal disease to evaluate its therapeutic efficacy. We will investigate the mechanism underlying HGF ameliorating renal fibrosis by examining the regulation of myofibroblast activation and TGF-Beta1 signaling. These will be accomplished in the following three specific aims: 1) to evaluate the efficacy of HGF gene therapy for chronic renal fibrosis; 2) to investigate the role of HGF in renal myofibroblast activation; 3) to elucidate the molecular mechanism underlying HGF blocking pro-fibrogenic cytokine TGF-Beta1 signaling. These studies will provide fundamental information such as the feasibility and efficacy of HGF gene therapy for chronic renal diseases, and will eventually lead to new therapeutic strategies to human chronic renal fibrosis, which is otherwise incurable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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.

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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 •

Project Title: IGF-I AND PROGRESSION OF CHRONIC RENAL FAILURE IN RATS Principal Investigator & Institution: Moore, Leon C.; Physiology and Biophysics; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-SEP-2003 Summary: In chronic renal failure (CRF), glomerular sclerosis (GS), tubulointerstitial fibrosis, and microvascular injury are thought to be consequences of elevated intravascular pressures that injure the kidney. The progression of CRF is accelerated by hypertension and loss of renal autoregulation. Insulin-like growth factor-1 (IGF-I) increases glomerular filtration rate, and is under investigation for therapeutic use in children with CRF with growth hormone (GH) insensitivity. IGF-I activity is low in CRF owing to high serum levels of inhibitory IGF-I binding proteins. We have developed a hypertensive, rapidly-progressing model of CRF in growing rats that may be relevant to renal failure in those children most at risk for hypertension and renal insufficiency, including African-American children, and those with low birth weight and congenital low nephron number. We found that treatment with IGF-I lowers blood pressure, preserves renal function, reduces the severity of GS, and completely prevents vascular injury, suggesting that IGF-I could slow the progression of CRF in children. The specific aims are: 1. To further characterize our model of CRF in young rats and the impact of IGF-I therapy by a) conducting longer-term (8 week) studies of the effect of IGF-I therapy on the progression of CRF, b) examining the effects of IGF-I therapy in young rats with established progressive CRF, c) to define residual renal function in untreated and IGF-I treated growing rats with CRF and how this is influenced by food intake, and d) defining the effects of IGF-I therapy in adult rats with CRF. 2. To test the hypothesis that the beneficial effects of IGF-I in CRF can not be fully attributed to its antihypertensive action. To determine if endothelin-1 receptor blockade reduces hypertension and progression CRF. 3. To test the hypothesis that the loss of renal autoregulation is an early event that precedes the development of both vascular injury and glomerular injury in CRF. 4. To determine if the beneficial effects of IGF-I on the progression of CRF are compromised by co-treatment with GH. 5. To identify the mechanisms through which acute treatment with IGF-I is able to restore autoregulatory ability in growing rats with CRF, and the extent to which abnormalities in vascular reactivity in CRF are mediated by elevated NO production. Rats will be 5/6 nephrectomized shortly after weaning, and studied 4-8 weeks later. A variety of techniques will be used, including vessel perfusion in vitro, renal clearance analysis in vivo, and histological, immunocytochemical, and Western analyses. The proposed studies will be the first comprehensive, direct investigations of the pathophysiology of the renal microvasculature in CRF, and of the effects of chronic IGF- I therapy on progressive CRF in growing rats. The results may have therapeutic implications for children with progressive renal insufficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPACT OF PANCREAS-KIDNEY TRANSPLANTS ON RENAL ALLOGRAFT Principal Investigator & Institution: Israni, Ajay K.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-JAN-2003 Summary: (provided by applicant): Simultaneous pancreas kidney transplantation (SPK) is an increasingly common treatment option for patients with end-stage renal disease due to Type I diabetes (DM). Recent studies suggest SPK may improve kidney allograft survival compared to kidney transplantation alone (KA). However, patient selection may account for this disparity since patient sociodemographics and comorbidities likely impact consideration for SPK. The objectives of this study are to assess the impact of patient selection on access to SPK versus KA and to determine the impact of SPK on renal allograft survival. In order to avoid selection bias, the comparison of renal allograft survival between SPK and KA recipients will be limited to patients waitlisted for SPK: approximately 10 percent of patients listed for SPK receive a KA due a fatty or traumatized pancreas allograft, or availability of a zero-antigen mismatch kidney alone. The USRDS has collected comorbidity data since April 1995. To assess the impact of patient selection on access to SPK we will use these national data to conduct a cross-sectional study of DM patients waitlisted for either SPK or KA after April 1995. We will compare patient socioeconomic demographics, comorbidities, and transplant center characteristics between these two groups. Logistic regression will be used to identify independent determinants of access to SPK. To determine the impact of SPK on renal allograft survival, we will conduct a retrospective cohort study of all patients waitlisted for SPK and transplanted with SPK or KA after April 1995. Renal allograft survival in SPK and KA will be compared using Cox proportional hazards models, adjusting for patient and transplant center characteristics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROVED REMOVAL OF PROTEIN-BOUND TOXINS IN DIALYSIS Principal Investigator & Institution: Collins, Gregory R.; Nephros, Inc. Audubon Technology Center New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): End Stage Renal Disease (ESRD) is associated with an accumulation of "uremic" toxins in essentially three categories: small water-soluble compounds, larger middle molecules, and small protein bound molecules. Current treatment modalities do not address the removal of small protein-bound substances. This research targets an ionic-hemodiafiltration-based product that removes small protein-bound solutes from blood; this function is not addressed by existing technology. This can be an extension of our unique multistage diafiltration process, with two diafiltration steps in series and substitution fluid added in a middilution mode (US Patent #6303036); or can be integrated with standard dialysis technology. An agent is added to dialysate fluid entering a first stage, causing an ionic (pH) shift of the blood, thereby dissociating a significant portion of protein-bound toxins from their conjugated protein counterparts. Once unbound, the small toxins are transported across a semipermeable membrane by diffusive/convective mechanisms. A second stage acts to return the ionic-altered blood to a normal condition before reinfusion. This Phase I research will qualify agents to be added to the dialysate fluid entering the first stage, so as to ensure safety and efficacy. PROPOSED COMMERCIAL APPLICATION: As of 2001, there were over 300,000 ESRD patients in the US, served by over 60,000 dialysis

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machines; this market is expected to exceed $500 million annually by 2008. Incorporating ionic technology will provide the unique benefit of removing proteinbound toxins, thereby reducing various comorbid conditions associated with toxic accumulation, improving overall patient health, and reducing associated hospitalizations, currently representing a $600 million+ annual expenditure. Additional applications include treatment of patients intoxicated with poisons or drugs with known protein binding characteristics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDUCIBLE DYSPLASTIC NEPHROPATHY IN B2-DEFICIENT MICE Principal Investigator & Institution: El-Dahr, Samir S.; Professor; Pediatrics; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2004; Project Start 01-MAY-2000; Project End 31-MAR-2008 Summary: (provided by applicant): Abnormalities of kidney and urinary tract development are the most common cause of chronic renal failure in children. While monogenetic renal dysgenesis syndromes continue to be unraveled, a sizable proportion of cases are sporadic and considered polygenic or a result of gene-environment interactions. During the previous funding period, we developed and characterized a unique mouse model of renal dysgenesis that is produced by defined gene-environment interactions. This animal model demonstrated that the bradykinin B2 receptor (B2R) is required for normal renal development under conditions of fetal stress. In response to gestational salt loading, B2R-null fetuses acquire a dysplastic renal phenotype characterized by excessive apoptosis, stromal expansion, and suppressed differentiated gene expression. Two independent lines of evidence support a central role for aberrant p53 activation in mediating the renal dysgenesis. First, the dysplastic kidneys overexpress a pro-apoptotic form of p53, P-Ser46-p53. Second, genetic crosses resulting in germline p53 haploinsufficiency rescue kidney development in salt-stressed B2R-null mutants. The long-term objective of this proposal is to elucidate the pathways leading to aberrant p53 activation and disruption of terminal epithelial differentiation in the developing kidney. Specific Aim 1 will test the hypothesis that induction of p53 in B2Rnull embryos is kidney-restricted and is accompanied by activation/expression of upstream p53 stress-induced kinases. Specific Aim 2 will determine the direct role of PSer46-p53 in the pathogenesis of the renal dysgenesis using two complementary genetic approaches. The first involves p53 gene dosage reduction in the germline of B2R-null mice; the second, generation of B2R null mice harboring a mutant Ser46-to-Ala p53 allele. We postulate that, in both cases, the B2R-null progeny will be protected from the renal dysgenesis. Specific Aim 3 will test the hypothesis that P-Ser46-p53 suppresses differentiated gene expression through recruitment of histone deacetylases (HDAC) to the promoter regions of terminal differentiation genes. In addition, we will explore the potential therapeutic benefit of HDAC inhibitors in the restoration of terminal differentiation and halting progression of the renal dysgenesis. We anticipate that new pathogenetic paradigms and therapeutic strategies will emerge from our studies that can hopefully be applied for the treatment of renal dysgenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IRON DELIVERY VIA HEMODIALYSATE IN ESRD Principal Investigator & Institution: Gupta, Ajay; Internal Medicine; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2006

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Summary: (provided by applicant): Erythropoietin (EPO) is an effective therapy for anemia of end-stage renal disease (ESRD) and is used in almost all ESRD patients receiving chronic hemodialysis. EPO stimulated iron utilization, coupled with small but unavoidable loss of extra corporeal blood with hemodialysis, leads to iron deficiency in almost all patients. Adequate iron delivery, by oral or parenteral supplementation, is necessary for optimal EPO action. Compliance with oral iron is poor due to gastrointestinal toxicity. Therefore intravenous (i.v.) iron is administered to 50-75 percent of hemodialysis patients, either intermittently when iron deficiency develops or at regular intervals to prevent iron depletion. Parenteral iron is a pro-oxidant, and may increase the risk of infections, inflammation and atherosclerosis by further enhancing oxidative stress and inflammation present in the majority of hemodialysis patients. Unlike the large polymeric iron complexes that are administered i.v., ferric pyrophosphate (FePPi), a monomeric iron salt (745 Da), can be delivered directly into the circulation when added to dialysis solutions. Fe(III) complexes tightly with pyrophosphate (PPi), thereby reducing dissociation and release of free iron. PPi anion is an antioxidant that promotes direct delivery of iron to transferrin, and iron transfer from transferrin to ferritin. FePPi is highly soluble in the acid concentrate and a concentrate fortified with FePPi can be used to generate a dialysate with defmed concentration of FePPi (Fe-HD). This is a double-blinded, randomized, controlled Phase II clinical trial to determine the safety and efficacy of FePPi added to the hemodialysis solutions in ESRD patients over a period of 9 months. Iron replete patients in=30) with no evidence of iron overload (transferrin saturation or TSAT< 40 percent, and ferritin < 800 lag/L), who have needed intravenous iron in the previous 2 months will be enrolled. Patients will be randomized to receive hemodialysis using Fe-HD or C-HD with every dialysis session for a total period of 9 months. The initial dose of dialysate iron will be 9 lag/dl if TSAT is 30-40 percent, and 11 lag/dl if TSAT is < 30 percent. Serum iron parameters (TSAT and ferritin) will be monitored every month. The dialysate iron concentration will be reduced to 9 lag/dl if pre-dialysis TSAT increases to 35-40 percent, and dialysate iron will be held if TSAT exceeds 40 percent. Dialysate iron will be restarted at 11 lag/dl if TSAT is < 30 percent and at 9 lag/dl if TSAT is 30-40 percent. Patients in both groups will receive 500 mg i.v. iron saccharate (Venofer(r)) in 5 divided doses at 5 consecutive dialysis sessions if TSAT is 800 lag/L). The acute and chronic effects of dialysate iron on serum levels of catalytically active iron and markers of inflammation and oxidative stress will be measured at the beginning and the end of the study. This Phase II study will provide preliminary evidence of the safety and efficacy of ferric pyrophosphate infusion via the dialysate, with the aim of preventing iron deficiency, and pave the way for a large, clinical trial of dialysate iron therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IRON IN KIDNEY DISEASE Principal Investigator & Institution: Guadiz, Ramon; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: Patients with chronic kidney disease (CKD) develop anemia due primarily to deficient production of erythropoeitin (EPO). Administration of EPO to patients with end-stage renal disease (ESRD), stimulates erythropoiesis and often leads to functional iron deficiency. Furthermore, iron losses are high, particularly in the hemodialysis patient. Patients are frequently non-compliant with oral iron supplements due to associated gastrointestinal side-effects. Oral iron supplements frequently fail to maintain adequate iron stores in EPO-treated hemodialysis patients. The use of i.v. iron has been

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shown to increase hemoglobin, and may therefore improve quality of life, and reduce morbidity and mortality in uremic patients. However, life-threatening/serious acute reactions to i.v. iron have been reported. Recent evidence suggests that i.v. iron leads to oxidative stress in ESRD. Oxidative stress, universally present in ESRD, has been implicated as one of the causes of atherosclerosis and resulting high morbidity and mortality from coronary artery disease, strokes and gangrene in these patients. To explore delivery of iron via the dialysate, ferric pyrophosphate (FePPi), the most stable and nontoxic of all monomeric iron salts has been selected. The present study will test the safety and efficacy of FePPi delivery via the dialysate in preventing iron deficiency, in chronic hemodialysis patients. The specific aims of this study are as follows: 1 ) To determine the efficacy of hemodialysis solutions containing ferric pyrophosphate in preventing the development of iron deficiency, compared with the conventional hemodialysis solutions. 2) To determine the safety of hemodialysis solutions containing ferric pyrophosphate, compared with the conventional hemodialysis solutions, by monitoring adverse reactions manifesting clinically or on laboratory testing. 3) To study catalytically active iron on markers of inflammation and oxidative stress 4) To study the effect of dialysate iron on dialyzer reuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATIENTS

ISLET

TRANSPLANTATION

IN

NON

UREMIC

DIABETIC

Principal Investigator & Institution: Gores, Paul F.; Carolinas Medical Center Box 3286, 11000 Blythe Blvd Charlotte, Nc 282322861 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (adapted from the application) The recent development of a steroid-free protocol of immunosuppression by Shapiro, et al, based on sirolimus and tacrolimus, has been a major advance in the field of islet transplantation. Insulin independence has been achieved in seven of seven consecutive cases by the University of Alberta group. Intervention was relatively early; none of the patients had chronic renal failure. However, in this series patients were not rendered insulin independent after receiving islets from the first donor pancreas and a second transplant from another donor was required before insulin therapy could be stopped. The primary barrier to successful human islet allotransplantation is cell mediated rejection. However, T cell mediated islet destruction is not the sole mechanism of islet graft injury after transplantation. Nonspecific host immune responses involving macrophages and macrophage generated byproducts are also detrimental to islet engraftment and function. The addition of an immunosuppressive molecule which is effective in combating these early non-specific host immune responses during the islet engraftment phase would be expected to improve the results of human islet transplantation. 15-deoxyspergualin (DSG) is an immunosuppressive molecule which inhibits many macrophage functions. It has been shown in experimental animal models to enhance early islet allograft function and has been used successfully in human cases of islet/kidney transplantation. The hypothesis to be tested in this research project is that the addition of an induction course of DSG to the immunosuppressive protocol of Shapiro, et al, will result in the achievement of insulin independence after islet transplantation from a single donor pancreas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISOFLAVONES:ACUTE RESPONSE IN CHRONIC RENAL FAILURE Principal Investigator & Institution: Fanti, Paolo; Associate Professor; Internal 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: LINKAGE CONSORTIUM FOR END-STAGE RENAL DISEASE Principal Investigator & Institution: Elston, Robert C.; Professor; Epidemiology and Biostatistics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The geriatric population in the United States is the most rapidly expanding age group with individuals over age of 65 comprising approximately 12% of the US population. End stage renal disease (ESRD) is a major health problem in this population with an incidence that has been steadily increasing over the last 10 years. More than 70% of ESRD in this population is associated with either diabetes mellitus and/or hypertension. The remaining 30% can be ascribed to other causes, including glomerulonephritis. Numerous studies have suggested that genetic predisposition to diabetic nephropathy, but genes for nephropathy have not yet been identified. We and

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others have hypothesized that ESRD is a complex disease with multiple genes and environment potentially contributing to its etiology. Because of the complexity of ESRD, identification of genes for this disease may prove difficult. Lessons learned from genetic research in other complex diseases such as diabetes, hypertension, asthma and obesity indicate that a concerted effort to establish a standardized collection of clinically welldefined families will prove beneficial in the discovery of ESRD genes. We propose to form a Genotyping and Data Coordinating Center (GADCC) for ESRD that will enable six different participating centers (PICs) to collect data from ESRD clinical populations ascertained through well-defined inclusion and exclusion criteria. To achieve this goal we will: (1) Establish an ESRD consortium, comprised of members from six PICs, with oversight by members from the National Institute of Digestive and Kidney Disease, and the External Advisory Committee, (2) Construct a state-of-the-art database for management of data across all six institutions, (3) Provide molecular and statistical genetic expertise and resources to the members of the consortium to map genes for nephropathy. Our overall goal is to establish a network of investigators, with wellcharacterized clinical populations, who will facilitate mapping of genes for ESRD in a timely manner using novel molecular and statistical genetic technologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAPPING GENES FOR NEPHROPATHY IN TYPE 2 DIABETES Principal Investigator & Institution: Krolewski, Andrzej S.; Associate Professor; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: There is strong evidence that genetic susceptibility is necessary for the development of diabetic nephropathy. Our research so far showed that genes involved in susceptibility to diabetic nephropathy may be different in type 1 and type 2 diabetes. The proposed research aims to identify a putative gene on chromosome 7q that seems to contribute specifically to susceptibility to diabetic nephropathy in type 2 diabetes. In addition, we will search for other chromosomal regions that harbor a major susceptibility locus for diabetic nephropathy in type 2 diabetes. The study design is based on sib-pairs with type 2 diabetes that are discordant for diabetic nephropathy (DSP). These families will be used for linkage analysis as well as for association studies using the Sibling Transmission Disequilibrium Test (s-TDT) approach. The specific aims of the proposed research are: 1) To establish two panels of sibling pairs that are concordant for type 2 diabetes and discordant for diabetic nephropathy (DSP): Already recruited is a Screening Panel of 89 extended families to be examined further to increase the specificity of nephropathy diagnoses; To be recruited is an Extension Panel of at least 200 nuclear families having a DSP, and groups of cases and controls for studies of the genetics of diabetic nephropathy. 2) To examine the promising chromosomal region on chromosome 7q for a locus contributing to susceptibility to diabetic nephropathy in type 2 diabetes; 3) To search for other chromosomal regions segregating with diabetic nephropathy in the Panels of DSPs using a chromosome specific panel of genetic markers; 4) To narrow chromosomal regions with evidence of linkage by genotyping panels of DSPs for additional markers in those regions and to initiate positional cloning of susceptibility genes for diabetic nephropathy in the most promising regions. The research has great significance given the current "epidemic" of end-stage renal failure due to type 2 diabetes in the U.S. population. Further, based upon our existing data, the probability of identifying genes for susceptibility to diabetic nephropathy in type 2 diabetes is very high. The innovation of this proposal is the study of genetic susceptibility for diabetic nephropathy in type 2 diabetes using a DSPs study design.

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This study design seems to be more efficient in detecting linkage for nephropathy than the traditional ASP (affected sib-pair) design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MDRD LONG TERM FOLLOW UP STUDY Principal Investigator & Institution: Beck, Gerald J.; Acting Chairman; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 1999; Project Start 30-SEP-1984; Project End 30-SEP-2004 Summary: The Modification of Diet in Renal Disease (MDRD) Study was a randomized clinical trial, funded by NIDDK, to determine the effect of dietary protein restriction and strict blood pressure control on the progression of chronic renal diseases of diverse causes in 840 patients. The planned duration of follow-up was 2-4 years, hence, the rate of decline in glomerular filtration rate (GFR), rather than the incidence of renal failure or death, was the primary outcome. The full-scale trial ended patient follow-up in January 1993. The purpose of this proposal is for the Data Coordinating Center (DCC) to obtain long-term followup data on the study Cohort and to continue data analysis. The fullscale trial showed a beneficial effect of the low blood pressure goal in patients with proteinuria and suggested a beneficial effect of reduced protein intake in patients with advanced renal disease (baseline GFR 13-24 mL/min/1.73 m2). However, the length of follow-up was insufficient to determine the efficacy of the low protein diet in patients with moderate renal disease (baseline GFR 25-55 ml/min/1.73m2, N = 585). During 10 months of additional follow-up after the end of the full-scale trial, the number of patients in the GFR 25-55 group to reach renal failure increased from 31 to 55, and a trend suggesting a benefit of the low protein diet on renal failure or death emerged (relative risk 0.63, 95% confidence interval: 0.30 - 1.02, p=.056). Based on observed rates of GFR decline, the projected number of patients in this group to reach renal failure increases to 163 by 9/96 and 263 by 9/2000, providing a unique opportunity for a much more accurate evaluation of this outcome. The primary goals of further follow-up are to assess the long-term effects of the diet and blood pressure interventions on 1) the incidence of renal failure or death and 2) nutritional status and cardiovascular outcomes prior to and following renal failure. Another fundamental goal is to document the longterm progression of renal disease by relating the extensive data from the full-scale study to long-term patient outcomes from the extended follow-up phase. Patient outcomes would be assessed from data provided by the patient and family, physicians' offices, hospital discharge summaries, and the USRDS. A pilot study demonstrating the feasibility of obtaining follow.up information has been completed. The MDRD Study Group has reported many results from the MDRD Study. This proposal will maintain this activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

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 Ub-

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proteasome 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 •

Project Title: MOLECULAR MECHANISMS IN HEREDITARY NEPHRITIS Principal Investigator & Institution: Hudson, Billy G.; Chairman; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: Alport Syndrome is a hereditary disorder characterized by progressive nephropathy which is frequently associated with sensorineural deafness and ocular abnormalities. The nephropathy has been linked to a structural abnormality in the glomerular basement membrane (GBM) which is caused by mutations in the gene encoding the alpha3, alpha4 and alpha 5 chains of type IV collagen. The most common form is X-linked, in which over 200 mutations have been found in the COL4A5 gene encoding the alpha5 chain. These mutations interfere with the formation of the alpha3(IV)/alpha4(IV)/alpha5(IV) supramolecular network of type IV collagen. Most male patients have near normal kidney function at birth, which deteriorates over time leading to end-stage renal disease by mechanisms that are not understood. The central thrust of this proposal is to test the hypothesis that the progression to end-stage renal disease in X -linked hereditary nephritis evolves from a congenital malformation of the glomerular basement membrane (GBM) which involves COL4A5 mutations that arrest a developmental switch from the immature alpha1(IV)/alpha2(IV) network to the nature alpha3(IV)/alpha4(IV)/alpha5(IV) network, and the persistence of this immature network predisposes the GBM to proteolytic degradation. The cornerstone of the research plan is a use of the canine X-linked model of the human disease in which the COL4A5 gene mutation is a premature stop codon. The specific aims are: Aim 1: Determine the nature and timing of the switch from immature to mature GBM in normal dog kidney in comparison to affected male dogs. Aim 2: Determine which glomerular cells synthesize the alpha3(IV), alpha4(IV) chains. Aim 3: Examine the relationship between the expression of the alpha3(IV), alpha4(IV) and alpha5(IV) chains. Aim 4: Determine the temporal relationship at both the message nd protein levels of the expression of the alpha1(IV)-alpha6(IV) chains in normal dogs compared to affected male dogs during progression of their disease. Aim 5: Determine the susceptibility of type IV collage of GBM to proteolytic degradation in normal and affected male dogs. The achievement of these aims requires application of the techniques of molecular biology, biochemistry, immunochemistry and cell biology. It is anticipated that the achievement of the aims will yield new insights into the mechanisms underlying the pathogenesis of Alport Syndrome. An understanding of these mechanisms is fundamental to the development of therapeutic measures to correct the disorder by gene therapy or to delay progression to end stage renal disease.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MEDIATORS OF DIABETIC RENAL HYPERTROPHY Principal Investigator & Institution: Kyriakis, John M.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114

Associate

Professor;

Timing: Fiscal Year 2002; Project Start 01-MAR-1990; Project End 30-SEP-2002 Summary: (Adapted from the applicant's abstract) - Diabetic neuropathy progressing to chronic renal failure develops in 30-40% of individuals with type I diabetes and 5-10% of individuals with type II diabetes. As such, diabetic neuropathy is perhaps the major determinant of premature mortality in the type I diabetic. The renal disease characteristic of diabetes mellitus is marked by glomerular hypertension and mesangial cell hypertrophy and hyperplasia, as well as extensive remodeling of the glomerular basement membrane. These phenomena may arise as a result of the actions of vasoconstrictive vasoactive peptides, especially endothelin (ET-1) and angiotensin-II (AII). In addition, hyperglycemia itself, along with the physical stress of glomerular hypertension may contribute to glomerular hypertrophy and basement membrane remodelling. It has become clear that cellular signal transduction pathways play an important role in coupling vasoactive peptides to the biological consequences of diabetic neuropathy. Indeed, hyperglycemia, ET-1, and A-II, as well as mechanical/hypertensive stress can induce c-fos and c-jun. Thus a complete understanding of the cellular signal transduction mechanisms recruited by vasoactive peptides, hypertensive stress, and reperfusion inhjury is crucial to the development of more effective treatments for diabetic neuropathy. The investigators have identified two signaling networks which are strongly activated by ET-1 and hypertensive stress (cell stretching). These pathways have been shown to mediate fos and jun induction in response to a variety of stresssful stimuli by recruiting two subfamilies of the extracellular signal-regulated kinases (ERKs), the stress-activated protein kinases (SAPKs, also called JNKs) and p38. It is the goal of the next phase of this project to determine how the SAPKs and p38s are regulated by the divergent stresses of ET-1, cell stretching, and reperfusion injury, and how the SAPKs and p38 contribute to the pathogenesis of diabetic neuropathy. First, the investigator will use a combination of conventional biochemical assays to identify members of the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) family, presen in mesangial cells which activate the SAPKs and p38 and which are themselves regulated by ET-1, A-II, or cell stretching. Next, they will determine the mechanisms by which A-II, ET-1, and cell stretching in mesangial cells recruit G proteins to activate the SAPKs and p38s. In particular they will focus on trimeric and Ras superfamily G proteins, as well as MEK-kinase-1 (MEKK1), a Ser/thr kinase also thought to regulate the SAPK pathway. Finally, they will use adenoviral expression constructs to perturb SAPK and p38 activation in mesangial cells and examine the effects of these perturbations on two biological responses known to occur in mesangial cells during diabetic nephropathy: cellular hypertrophy and excess matrix deposition. These studies, they hope, will expand our knowledge of signal transduction in the diabetic kidney and contribute to the development of novel treatments for diabetic nephropathy using signaling components as targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MORTALITY & MORBIDITY IN HEMODIALYSIS PATIENTS Principal Investigator & Institution: Daugirdas, John T.; Professor; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2004

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Summary: This trial is designed to evaluate survival as well as a number of secondary outcomes (hospitalization for cardiovascular disease, infection, or other non-accessrelated causes, declining body weight, or declining serum albumin level) in patients randomly assigned to one of four groups: (A) moderate-dose dialysis, low-flux cellulose membrane, (B)high-dose dialysis, low-flux cellulose membrane, (C) moderate-dose dialysis, high- flux synthetic membrane, (D)high-dose dialysis, high-flux synthetic membrane. Each Clinical Center will randomize sufficient patients among these 4 groups such that at least 60 patients are enrolled at all times. The patients will be followed for a 5-year period, replacing deaths or dropouts as they occur with new patients. An 18-month recruitment phase is followed by a 5-year follow-up/intervention phase, and a 6-month closeout phase. Our Clinical Center is uniquely qualified to successfully participate in this study. It is a partnership between the University of Illinois College of Medicine and West Suburban Kidney Centers, a corporation of 14 dialysis units treating 1400 patients in the Chicago area. The study will be performed at the University of Illinois dialysis unit, as well as in 3 nearby units of the WSKC. According to the patient eligibility criteria set out by the Draft MMHD Protocol, we already have identified 220 patients in these 4 units who are eligible for the study and who also meet additional desired criteria (no gross non-compliance, no history of substance abuse, feasibility of delivering a 2-pool Kt/V of 1.4). The centralization of the administrative structure of the WSKC units, which extends through nursing, dietetics, social work, and technologists, and the centralized data gathering systems already in place, will greatly facilitate the coordination among units to complete the study. Appropriate technology to carry out high-efficiency dialysis is in place in each of the primary units. More than 80% of the dialysis stations in the primary units have volumetric UF controlled-machines capable of blood flows > 500 ml/min and dialysate flows of 800 ml/min. A dialyzer reuse program with excellent quality controls allows for use of high efficiency dialyzers which will be necessary to deliver the high-dose dialysis treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MORTALITY AND MORBIDITY IN HEMODIALYSIS PATIENTS Principal Investigator & Institution: Allon, Michael; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2004 Summary: End-stage renal disease (ESRD) is associated with a markedly reduced patient survival and substantial morbidity. The life expectancy of a 40 year-old dialysis patient is 8.8 years, as compared with 37.4 years for the general U.S. population of the same age. Retrospective studies have suggested that higher Kt/V and use of dialysis membranes with higher flux and greater biocompatibility may decrease morbidity and mortality in maintenance hemodialysis patients, but few prospective studies have evaluated the effects of such manipulations. This prospective, randomized, multicenter investigation will test the following hypotheses: (1) Hemodialysis achieving higher Kt/V results in decreased mortality in ESRD patients undergoing maintenance hemodialysis. (2) Hemodialysis with membranes of higher flux decreases mortality and morbidity. (3) These two interventions are safe and acceptable to hemodialysis patients. In-center hemodialysis patients will be randomized to receive dialysis treatments with either standard or high Kt/V (1.0 vs 1.4, double pool) and using either high flux membranes or low flux membranes. Subjects will be randomized to one of four experimental groups: a. Kt/V 1.40; High flux membrane b. Kt/V 1.40; Low flux membrane c. Kt/V 1.00; High flux membrane d. Kt/V 1.00; Low flux membrane All

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other aspects of the patients' medical and dialysis care will follow the usual standards of care. The study subjects will be followed prospectively for five years to determine: a. Patient mortality (primary endpoint) b. Patient morbidity (secondary endpoint) i. Nonaccess related hospitalization (especially cardiovascular events or serious infections) ii. Malnutrition (a decline in serum albumin) The results will be analyzed to determine whether there are significant differences in patient survival or morbidity among the four treatment groups. 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: 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,

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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 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: NONINVASIVE SPECTROSCOPIC SENSORS FOR GLUCOSE AND UREA Principal Investigator & Institution: Arnold, Mark A.; Professor; Chemistry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): A research plan is proposed to advance the development of noninvasive sensing technology for the in vivo measurement of glucose and urea in human subjects. The proposed approach is to pass a specific band of nearinfrared light through a selected measurement site on the body and then extract the desired analytical information from the resulting noninvasive spectrum. Results from our previous work demonstrate that 1) the combination spectral region is superior to all other near-infrared spectral regions for distinguishing glucose in complex biological matrices, 2) spectral quality is critical and RMS-noise levels of several micro-absorbance units (pAU) are necessary, and 3) sufficient sample thickness is required to provide distinguishable absorbance signals for analysis. Each of these requirements is satisfied in the proposed research plan. A customized Fourier transform near infrared spectrometer will be used to provide high quality combination spectra through human tissue with noise levels on the order of 2 pAU. A fiber-optic interface is proposed for collecting noninvasive spectra through a pinch of skin on the back of the hand or the septal cartilage of the nose. Each of these putative measurement sites possesses the appropriate thickness and chemical composition for successful glucose and urea measurements. For the first time, we have both the instrumentation and putative measurement sites that are compatible with noninvasive measurements with combination spectra. A series of in

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vitro experiments are proposed to characterize this system for the ability to measure glucose and urea with limits of detection of 2 and 1.5 mM, respectively. Animal models have also been identified for both measurement sites and will be used to rigorously establish the analytical utility of this approach. Finally, human subject experiments are proposed to obtain critical information about the human in vivo environment and to evaluate actual in vivo measurements of glucose and urea. Success will provide tremendous healthcare benefits arising from an improvement in the treatment and management of diabetes and end stage renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPTIMAL GLOMERULOSCLEROSIS

TREATMENT

OF

FOCAL

SEGMENTAL

Principal Investigator & Institution: Fine, Richard N.; Pediatrics; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Focal segmental glomerulosclerosis (FSGS) is the most common glomerular lesion leading to ESRD in Children. Approximately one-fifth of the steroid resistant patients with FSGS (SRFSGS) will respond to cyclospodne (CS). Those unresponsive patients will progress over a variable time interval to ESRD. The rate of progression is particularly severe in African-American and Hispanic children. To date no controlled trial with novel immunomodulatory agent(s) has demonstrated efficacy inducing a complete remission in SRFSGS patients who fail to respond to CS. The Specific Aims of this proposal are to compare two regimens: (a) low-dose CS and sirolimus, and (b) intravenous methylprednisolone and cyclophosphamide in patients with SRFSGS who do not respond with a complete remission to a 16 week course of CS and low-dose prednisone in order to determine which regimen is more efficacious with fewer side-effects. An additional Specific Aim will attempt to predict progression in patients with SRFSGS by Sirius Red staining and by detecting fibrogenic cytokines in renal biopsy tissue at enrollment and 18 months after randomization. Additionally, 125Iiothalamate will be compared with Cystatin C as a measure of glomerular filtration rate (GFR) in order to determine if the latter is an acceptable "gold standard" for serial measurement of GFR in patients with SRFSGS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND HEMODIALYSIS ACCESS FAILURE Principal Investigator & Institution: Weiss, Miriam F.; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Antioxidant treatment of human disease has met with mixed success. Factors that lead to oxidative stress in living systems are complicated, and as a result, the actions of antioxidants may seem paradoxical. There is a great deal of evidence for increased oxidative stress in uremia. The rationale for this proposal stems from emerging evidence for efficacy of vitamin E in uremia. The investigators believe that intimal hyperplasia in hemodialysis vascular access represents a unique model of oxidative damage to vascular tissue. Complications of hemodialysis access are a major cause of morbidity and the most frequent single reason for hospitalization among patients with end stage renal disease (ESRD). In vivo and in vitro, oxidative stress stimulates cell growth factors and regulatory mechanisms that lead to the characteristic lesion of access failure, intimal hyperplasia. The central

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hypothesis to be tested by this project is that oxidative stress is a major (and modifiable) pathogenetic trigger for vascular access complications in patients with ESRD. In elucidating the roles of oxidative stress in the pathophysiology of access failure, the goal is to discover diagnostic factors that can lead to accurate indications for antioxidant therapy. In testing antioxidant medication, the investigators hope to slow progression of intimal hyperplasia in hemodialysis access. Because antioxidant therapy is not currently routine in patients with uremia, the proposal is a pilot study. Data obtained in these specific aims will be used to design large-scale testing of the efficacy of vitamin E (alpha-tocopherol). Specific Aim A: To identify predictors of vascular access venous outflow stenosis or thrombosis, focusing on circulating and histologic markers indicative of the effects of oxidative stress. Specific Aim B: To determine the efficacy of chronic administration of an antioxidant (alpha-tocopherol) in the prevention of intimal hyperplasia and thrombosis of the hemodialysis access. Specific Aim C: To compare the success rates of prophylactic angioplasty when non-invasive techniques demonstrate decreased flow in the hemodialysis access in alpha-tocopherol-treated versus placebotreated patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOLOGY OF RENAL MATRIX METABOLISM Principal Investigator & Institution: Lovett, David H.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-MAR-2005 Summary: The progressive decline in renal function characteristic of most forms of renal disease is intimately associated with the development of glomerular and interstitial fibrosis. The extent of interstitial fibrosis closely predicts the ultimate clinical outcome in terms of development of end stage renal disease. Progressive interstitial fibrosis may be initiated by multiple factors, including immune injury, hypoxia, reduction in renal mass and diabetes mellitus; however, these insults converge to a final common pathway associated with tubular epithelial cell transdifferentiation to pro- sclerotic myofibroblasts and fibroblasts, This laboratory has focused on the role of specific matrix metalloproteinases in the initiation and perpetuation of the pro-fibrotic transdifferentiation of tubular epithelial cells. Specifically, coordinate expression of two matrix metalloproteinases, gelatinase A and MT1-MMP, appears to drive the transdifferentiation process in vitro and in vivo. The Specific Aims of this proposal are to define at the transcriptional level, with an emphasis on TGFbeta, common signaling pathways and transcription factors which link gelatinase A and MT1-MMP transcription. Secondly, a transgenic approach will be taken to examine the relationship between gelatinase A and MT1-MMP gene expression in a TGF-beta-driven model of progressive renal fibrosis. Finally, the ability of gelatinase A to directly induce interstitial fibrosis in vivo will be assessed using targeted conditional expression in the transgenic mouse. Taken together, these complementary approaches may provide important new insights into the mechanisms of progressive renal fibrosis and point out specific molecular targets suitable for new forms of therapies of these disabling disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

Project Title: PHYSIOLIGICAL GENOMICS OF HYPERTENSIVE RENAL DISEASE Principal Investigator & Institution: Jacob, Howard J.; Director, Human and Molecular Genetics c; Physiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): End-stage renal disease (ESRD) remains a major health problem in the United States, with an incidence that has been increasing steadily for more than a decade. More than 67% of ESRD is associated with hypertension and/or diabetes. The causes for these associations are not known. However, there is increasing evidence that susceptibility genes are likely to play a major role in determining a patient?s predisposition to ESRD. We have developed a comprehensive research program including genetics, genomics, rat transgenics and mechanism-based physiology to study the complex interaction between hypertension and susceptibility genes for renal disease. Here we propose to focus these tools on the following specific aims: 1. Complete the positional cloning of the Rf-1 gene. We identified this important QTL and propose to combine mapping and comparative genomics to locate the specific gene. 2. Determine pathways involved in the renal disease process using microarray technology. By identifying genes differentially expressed in normal and diseased kidney over the time course of ESRD development, we will see how gene expression is modified in the disease process. 3. Test our hypothesis that Rf-1 causes impaired renal autoregulation due to a lack of myogenic tone, resulting in glomerular hypertension and renal damage. We will also pursue mechanism-based studies of the QTL?s Rf-2, -3 and 5. 4. Study the Rf-1 locus by constructing transgenic rats carrying YACs. This will allow a direct test of any genes within the YAC. Transgenics will also be used to validate Rf-1. 5. Use comparative genomics to study human homologue of the Rf-1 region, Rf-1 gene and other candidate genes in humans. Using affected/unaffected human sibpairs, we

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will use SNP and sequence analysis to determine if individuals exhibiting ESRD show a significant association with sequence variants in candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT/FEASIBILITY PROGRAM Principal Investigator & Institution: Fogo, Agnes B.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-MAR-2007 Summary: Visceral glomerular epithelial cells (podocytes) are a component of the glomerular filtration barrier. Due to a lack of ability for post-natal proliferation, the podocyte is a most vulnerable component of the glomerulus, and podocyte injury triggers irreversible change sin many glomerular diseases. The ultimate goal of this project is to elucidate the molecular mechanisms of podocyte damage through the study of the pathogenesis of HIV-1 associated nephropathy (IVAN). In HIVAN, glomeruli show a characteristic change, i.e., collapsing focal segmental glomerulosclerosis (FSGS), in which podocytes lose differentiation markers, proliferative and undergo apoptosis. Similar podocyte dysregulation is observed in idiopathic collapsing glomerulopathy and the FSGS variant with cellular lesion. In addition, down-regulation of differentiation markers occurs also in more common glomerular diseases, including minimal change disease and mesangial proliferative glomerulonephritis. Previous transgenic mouse studies showed than when HIV-1 DNA containing vif, vpr, rev and tat is expressed by the authentic LTR promoter, the kidney develops a renal disease faithfully mimicking human HIVAN. Renal cross transplantation between the transgenic and wild-type mice revealed that the transgene expressed in the kidney causes the renal disease. Based on this information, the following specific aims will be investigated during the first two years. Aim #1. Generation of transgenic mice in which podocyte-specific expression of HIV-1 gene that is essential for the pathogenesis of HIVAN by transgenic mice. These studies will be followed by identification of the specific molecule(s) in podocytes that are associated with the product of the pathogenic HIV-1 gene to ascertain the common mechanism(s) of podocyte dysregulation. Genetic studies of inherited polycystic kidney disease (PKD) in human and animal models have clearly shown that mutations at multiple loci result in various forms of PKD. While the cystogenesis itself is thought to be a primary cause of renal injury, several studies have stressed the important relationship between the onset of tubulointerstitial fibrosis, and the progression to endstage renal disease. The PI has characterized a mouse model for PKD caused by three independent mutations, kat, kat21, kjat3J, that map to the same locus on Chromosome 8. By positional cloning, she has identified the gene mutated as the NIMA (Never In Mitosis A) related kinase, Nek1. The PI hypothesizes that in the kidney, NEK1 protein belongs to a signaling pathway that promotes the full maturation in renal tubular epithelial cells. The PI has also shown that the loss of Nek1 function leads to an increase in TGFbeta1 mRNA levels in renal interstitial as well as tubular cells. Therefore, these altered/immature renal epithelial cells may not only facilitate renal cystogenesis but also contribute directly to tubulointerstitial fibrosis. The PI is currently examining in her funded RO1 how the loss of Nek1 function leads to renal cystogenesis. In this pilot proposal she will pursue a new area of research: investigating the role of Nek1-null tubular epithelial cells in interstitial fibrosis. The hypotheses to be tested are: 1. The loss of Nek1 expression in renal tubular cells increases the activation of TGFbeta1 in those cells 2. The loss of Nek1 expression in renal tubular cells increases epithelialmesenchymal transdifferentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEOMIC ANALYSIS OF DIABETIC NEPHROPATHY Principal Investigator & Institution: Klein, Jon B.; Professor; Medicine; University of Louisville Jouett Hall, Belknap Campus 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 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

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Project Title: QUANTITATIVE EXPRESSION LIBRARIES TO IDENTIFY ESRD GENES Principal Investigator & Institution: El-Meanawy, M A.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Chronic renal failure frequently progresses to end stage renal disease (ESRD), resulting in significant morbidity, mortality and economic burden to the health care delivery system. The lack of effective therapies for chronic renal failure is partly a testament to the complex nature of the disease. Accumulating evidence suggests that genetic predisposition plays important role in the progression of chronic renal failure to ESRD. To date, no nephropathy susceptibility gene(s) have yet been identified in humans, despite the efforts of multiple laboratories using classical genetic methods, including gene mapping and loci scanning. We propose

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to utilize an animal model for ESRD (the oligosyndactyly mouse) to try to identify genes that might be involved in the pathogenesis and/or affect the progression of chronic renal failure to ESRD. We adopted an empiric approach utilizing a novel powerful technique called serial analysis of gene expression (SAGE) that will allow systematic analysis and comparison of gene expression libraries in diseased animals and their wild type controls. Our Specific Aims are: 1) To generate SAGE expression libraries from kidneys of ROP-Os/+, C57BL/6-Os/+, ROP-+/+, and C57BL/6-+/+ mice, and 2) To analyze the expression libraries using Monte Carlo simulation analysis and hierarchical clustering to identify candidate genes and pathways involved in renal disease pathogenesis. An algorithm is proposed to prioritize candidate genes identified by these analyses of the libraries. Functional analysis of these genes will be performed in future studies using standard molecular and genetic techniques, which will allow us to learn more about pathways critical for renal disease pathogenesis. Ultimately, this might pave the way to the development of new therapeutic and/or diagnostic modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAE 1 AND RENAL INJURY Principal Investigator & Institution: Lu, Christopher Y.; Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: Hypothesis: We recently found that ischemia induces the de novo expression of RAE 1. on renal tubules and the renal expression of NKG2D, the leukocyte receptor for RAE 1. We propose that the expression of RAE 1 allows injured renal epithelia to be recognized by leukocytes via NKG2D. This recognition activates the leukocytes and exacerbates injury. In addition, this recognition may initiate a "RAE 1- NKG2D vicious cycle" of epithelial injury -> RAE 1 expression -> NKG2D leukocyte activation -> epithelial injury -> RAE 1 expression, etc. This may contribute to the progressive nature of renal failure. The overall goal of this R21 (RFA pilot and feasibility program related to the kidney, PA-01-127) is to test the above hypothesis. Although our proposal is currently focused on ischemic acute renal failure, expression of RAE 1 may also occur in other types of renal injury, including progressive renal failure in diabetes mellitus and hypertension, and contribute to perpetuating the injury in those diseases. Specific Aim I: Progressive renal insufficiency develops over 20 weeks after severe renal ischemia in published models; when during this period are RAE1 and NKG2D expressed? Specific Aim II: Determine which NKG2D-expressing leukocyte(s) contribute to renal injury after ischemia. Such leukocytes may include NK cells, NK T cells, macrophages, CD8 T cells, and/or T cells. Determine if progressive renal failure is prevented by eliminating specific populations of these leukocytes using transgenic knockout mice, and monoclonal antibodies. Specific Aim III: Examine the regulation of RAE 1 expression on renal tubule cells in vitro and in vivo. The "RAE 1 - NKG2D vicious cycle" proposed here would be a novel insight into progressive renal injury. New therapy might be directed at interdicting this vicious cycle. 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

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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 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: RENAL BONE DISEASE Principal Investigator & Institution: Malluche, Hartmut H.; Professor of Medicine and Chief; Internal Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 15-AUG-1996; Project End 31-JUL-2005 Summary: (provided by applicant): The proposed continuation studies are designed to investigate the most important current issues of bone disease in patients with end-stage renal disease (ESRD) requiring dialysis: 1) the relationship between parathyroid hormone (PTH) and bone turnover and 2) the need for noninvasive diagnosis of the various types of renal bone disease. ESRD has a prevalence rate of 1,105 per million Americans, and African-Americans make up 30 percent of ESRD patients in contrast to 12.6 percent of the general population. In addition, African-Americans have lower bone turnover than Caucasians. ESRD patients with low bone turnover have been shown to have higher morbidity and mortality, and, under this grant, it was established that incidence of this form of renal bone disease is increasing. Identification of ESRD patients with high bone turnover is also important because they can benefit from several current treatment modalities. Employing a novel PTH assay recognizing the 1-84 PTH molecule,

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preliminary studies from this grant revealed differing ratios between 1-84 PTH and its amino-terminally truncated (NT-2-t PTh) fragment(s) in ESRD patients with high and low bone turnover. The central hypothesis of the application is that NH2-t PTH fragment(s) antagonize(s) 1:84 PTH effects on bone. Since NH2-t PTH fragments have been suggested to blunt 1-84 PTH effects, the proposed studies will investigate the antagonistic role and the potential mechanism(s) of NH2-t PTH on 1-84 PTH effects on bone. Moreover, the diagnostic value of 1-84:NH2-t PTH ratio for assessment of bone turnover will be established in ESRD patients. In addition, the effect of calcium on 184:NH2-t PTH ratio will be investigated. Studies will be done in ESRD patients and experimental rats with normal and reduced kidney function employing a) the novel 1-84 PTH assay and the established "intact" PTH assay for calculation of NH2-t PTH fragment(s), b) classical histomorphometry for assessment of bone turnover, and c) molecular morphometry of bone cells to assess apoptosis and osteoprotegerin ligand expression for evaluation of PTH action on bone. The anticipated results of the proposed studies will help understand the clinically relevant relationship between 1-84 PTH, NH2-t PTH fragment and bone turnover. It will be established whether AfricanAmerican ESRD patients are at particular risk to accumulate NH2-t PTH and thus are prone to develop adynamic bone disease with its far-reaching clinical consequences. Moreover, the forthcoming data will open new avenues for rational approaches to diagnosis and therapy of renal bone disease, one of the major unresolved problems in ESRTI) patients Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RENAL FAILURE GENES IN THE SOUTHEASTERN US Principal Investigator & Institution: Freedman, Barry I.; Professor and Chief; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The purpose of this study is to identify the genes causing diabetic and nondiabetic renal failure (RF) in high risk black and white families residing in the southeastern United States. Diabetes is the most common cause of end- stge renal disease (ESRD) in the U.S. At most, 30% of diabetic patients are susceptible to RF with its progression to ESRD and high mortality rate. Selected diabetic families demonstrate multi-generational clustering of renal disease. An inherited basis for RF is also supported by reports that blacks are more likely than whites to develop RF. These racial differences are not fully explained by racial differences in prevalence or severity pf diabetes mellitus or hypertension, socioeconomic factors or access to healthcare. In order to identify genes causing RF we will continue to identify, clinically characterize, and collect DNA from 400 families (200 black, 200 white) with type 2 diabetic ESRD index cases and additional first degree relatives with type 2 diabetes mellitus. This phase of the project employs the unique "Family History orf relatives with type 2 diabetes mellitus. This phase of the project employs the unique "Family History of ESRD" database, independently compiled by the federally-funded ESRD Network 6 (Southeastern Kidney Council). This registry currently contains family history data from more than 20,00 incident patients with ESRD who started dialysis after September, 1993. Approximately 60% of patients are black and 40% have diabetic RF. Candidate genes will be screened for linkage to RF at the Wake Forest University Baptist Medical Center, and DNA and clinical data will also be supplied to the study's Genetic Analysis and Data Coordinating Center (GADCC) for a comprehensive genome wide survey to identify novel loci causing RF. The identification of RF genes would form a genetic basis

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for detection of high risk individuals and lead to the development of intervention and treatment strategies for prevention of kidney disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH CENTER TO REDUCE ETHNIC DISPARITIES IN ESRD Principal Investigator & Institution: Callender, Clive O.; Professor; None; Howard University Washington, Dc 20059 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Substantial racial/ethnic disparities exist in the area of renal health. Minority groups are more than 50% of all persons on the waiting list for a kidney transplant in the United States. Yet, because minorities donate organs at a rate that reflects their representation in the population, the shortage of kidneys for minorities with End-Stage Renal Disease has reached crisis proportions. Such trends suggest that in addition to conducting research that can better define the correlates and causes of racial/ethnic disparities in kidney transplantation rates research is also needed to identify psychosocial and psychoneuroimmunological factors that contribute to poorer health outcomes. The findings can be exported to the design of prevention campaigns and that can efficaciously reduce the prevalence of hypertension, diabetes mellitus, poor nutrition and inadequate exercise, and licit and illicit substance use among minorities. The Howard University Project Export Center of Renal Health will be structured to serve as an institutionalized and permanent research center that will complete research and test interventions and practices that can reduce current racial/ethnic differentials in renal health. The Center will be headed by Dr. Clive O. Callender, the nation's premiere kidney transplantation specialist and a pioneer in creating interventions to remedy racial/ethnic gaps in renal health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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

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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 •

Project Title: SHIGA TOXIN 1:UPTAKE MECHANISMS AND INTRACELLULAR ACTION Principal Investigator & Institution: Kovbasnjuk, Olga N.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Foodborne diarrheal disease cause 76,000,000 cases each year in the United States. Intestinal pathology caused by Shiga toxin-producing Escherichia coli (EHEC), important food-borne pathogens, includes approximately 35% of all bloody diarrhea in the United States, an unknown % of watery diarrhea, and the life-threatening systemic manifestations (observed in up to 10% of cases) of infection, the hemolytic uremic syndrome (HUS) and encephalopathy. EHEC are the leading cause currently of acute and chronic renal failure in children in the USA. EHEC is a particularly worrisome foodborne pathogen, because the number of outbreaks caused by EHEC continue to significantly increase and there is no effective specific therapy for this illness which is lethal in up to 10% of children who develop HUS. Thus, there is a great need to better understand the pathogenesis of this infection to promote development of new therapeutic approaches to treat EHEC infection and its complications. Understanding the complex mechanism of Stx uptake and trafficking pathways into colonic epithelium may help to identify new drug targets and develop new strategies directed at preventing toxin action on human intestine. In this application we will study the mechanism of Stx1 and its B-subunit (Stx1B) uptake, trafficking and intracellular action using animal and human intestinal epithelial cell models. In Aim 1 we will study the role of lipid rafts (LR) in Stx1/Stx1B translocation across the apical cell surface. We propose to test the role of LR proteins, which are associated with toxin receptor in toxin translocation machinery. In Aim 2 we will study a newly recognized Stx1/Stx1B internalization pathway from plasma membrane into the nucleoli. In Aim 3 we will study the mechanisms of Stx1/Stx1B-induced apoptosis and its role in toxinrelated intestinal inflammation. These proposed studies should provide new insight into the understanding of the molecular basis of Stx-mediated intestinal epithelial cell injury and facilitate the design of strategies to prevent Stx1 uptake and intracellular action, and thus serve to find new targets to interfere with EHEC-related gastrointestinal pathophysiology. 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

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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 •

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

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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 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: TGF-BETA1 AND EXCESS RENAL DISEASE IN AFRICAN AMERICANS Principal Investigator & Institution: Suthanthiran, Manikkam; Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract) The overall objective of this project is to identify mechanisms responsible for end stage renal disease (ESRD), a common disease (73,091 incident cases in 1996) of extraordinary personal suffering and societal costs ($14.55 billion in 1996), and one that is associated with an adjusted death rate of 24% in the first year, despite renal replacement therapy. The specific objective of this application is to test the hypothesis that hyperexpression of transforming growth factor beta (TGF-beta), a multifunctional cytokine clearly shown to induce renal disease in experimental models, is a risk factor for the progression of renal disease to ESRD in humans. That TGF-beta1 over expression is more frequent in African Americans, a population at greater risk for ESRD than Caucasians, and that TGF-beta1 expression is determined, at least in part, by TGF-beta1 DNA polymorphisms will be explored in this study with conceptually interrelated clinical and laboratory studies. The specific aims are as follow. Specific Aim 1 is to identify ESRD-specific differences in TGF-beta1 genotype and phenotype. A discordant sib pair study stratified by race will be performed to determine whether candidate TGF-beta1 DNA polymorphisms are linked to ESRD. African American and Caucasian ESRD patients will be studied to test the hypothesis that TGF-beta1 hyperexpression (increased mRNA and protein levels) is more frequent in 1) ESRD patients compared to a healthy sibling, and 2) African Americans compared to Caucasians. Specific Aim 2 is to test the postulate that TGFbeta1 DNA polymorphisms and TGF-beta1 hyperexpression are more frequent 1) in patients with hypertension compared to age-, gender-, and race-matched normotensive acquaintances, and 2) in African Americans compared to Caucasians. Specific Aim 3 is to test the postulate the TGF-beta1 hyperexpression and TGF-beta1 DNA polymorphisms are correlates of the rate of decline of renal function and the development of adverse renal endpoints in African American and Caucasian children with chronic renal insufficiency. TGF-beta1 phenotype and genotype will be determined at baseline in children followed prospectively by the North American Pediatric Renal Transplantation Cooperative Study (NAPRTCS) Chronic Renal Insufficiency (CRI) Registry. Children (stratified by race) with focal and segmental glomerulosclerosis (FSGS) demonstrated by biopsy will be compared to children with non-immunologic renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TGF-BETA1 AND PAI-1 GENOTYPES IN CHRONIC KIDNEY DISEASE Principal Investigator & Institution: Rao, Madhumathi; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2004; Project Start 01-SEP-2004; Project End 31-AUG-2009 Summary: (provided by applicant): Patients with chronic kidney disease (CKD) are at higher risk of developing CVD including atherosclerotic cardiovascular disease (ASCVD), compared to the general population, and this increased risk is unexplained by traditional risk factors for CVD. The role of genetically determined variants of key mediators of CVD under-explored. The Principal Investigator (PI) has designed a rigorous training program that will provide her with the necessary skills, experience and opportunities to develop into an independent investigator in the field of genetic epidemiology in relation to chronic kidney disease. She will obtain a Masters of Science in Clinical Care Research with special emphasis on genetic epidemiology, 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. Her mentors have extensive experience in clinical and laboratory investigation of CKD and, ESRD, and in clinical and translational research in Nephrology. Transforming growth factor-beta (TGF-beta1) and Plasminogen activator inhibitor-1 (PAl-1) play key regulatory roles in atherogenesis and kidney disease progression, and interact with angiotensin II (All) and each other. The hypotheses to be investigated are that functionally relevant single nucleotide polymorphisms (SNP) in the promoter and coding regions of TGF-beta1 and in the promoter regions of PAl-1 contribute to cardiovascular risk in patients with CKD. The Specific Aims are to 1) determine the frequency of SNP's of TGF-beta1 and PAl-1 in patients with CKD 2) examine their relationship to plasma levels of TGF-beta1 and PAl1 respectively and 3) Evaluate their relationship to the prevalence and progression of ASCVD, as measured by carotid ultrasound intima-media thickness, ankle-brachial index and clinical ASCVD. The research project is achievable and promises to provide new insights into the importance of genetic factors as novel markers of cardiovascular risk. The results may help identify patients who could benefit from maximal All blockade or anti-fibrogenic therapies. The PI has assembled a team of scientists to assist in the conduct of the project and convened an internal and external scientific advisory committee to monitor her progress. The proposed training program and research project will prepare her for a career as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 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

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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: THE EFFECTS OF HEMODIALYSIS ON THE SLEEP/WAKE CYCLE Principal Investigator & Institution: Parker, Kathy P.; Associate Professor; Adult and Elder Health; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-DEC-2007 Summary: (provided by applicant): Approximately 50 to 85% of patients with end-stage renal disease on chronic hemodialysis (HD) have sleep complaints and/or sleep disorders-problems that are associated with decreased quality of life and functional health status. Thus, population specific interventions are needed that address both the underlying mechanisms and consequences of these abnormalities. We propose to test a novel application of an existing intervention-cool dialysate (often used to treat hypotension) as opposed to warm dialysate (standard treatment) during HD-for its ability to stabilize the sleep/wake cycle of chronic HD patients. Primary outcome variables include objective measures of nocturnal sleep and daytime sleepiness and selected sleep-related physiological, psychological, behavioral, and general health outcomes. A randomized, single-blinded (investigators) control group, experimental design will be used. Sixty-eight chronic HD patients, age 21 to 70 years, will be recruited and randomized into one of two groups, Group A (experimental) and Group B (control). For individual subjects, the study will (be) conducted over a 9-month period of time and divided into 3 phases-Phase I (3 months), Phase II (3 months), and Phase III (3 months). During Phase I, both groups of subjects will receive standard treatment (warm

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dialysate) and data regarding nocturnal sleep (objective and subjective measures of sleep latency, sleep efficiency, total sleep time, and sleep disturbance), daytime sleepiness (physiologic, manifest, and introspective), body temperature (distal/proximal skin gradient and axillary body temperature rhythms), psychological (mood), behavioral (daily activity/rest), and general health outcomes (quality of life and functional status) will be collected. During the next 3 months (Phase II), Group A will receive HD with cool dialysate while Group B will continue to receive standard treatment. During Phase III, both study groups will return to baseline treatment and receive HD with warm dialysate. In each Phase, data on all outcomes of interest will be collected. Data analysis will provide important information regarding the impact of this intervention on the sleep/wake cycle of HD patients and other related clinical outcomes. In addition, study results will make a significant contribution to the scientific understanding of how medical treatments may interact with normal systems to induce sleep/wake abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE SHORT-DAILY HEMODIALYSIS PILOT STUDY Principal Investigator & Institution: Levin, Nathan W.; Renal Research Institute Joint Venture 207 E 94Th St, Ste 3032 New York, Ny 10128 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Background: Hemodialysis is the majority treatment modality for renal disease, and improvements in its delivery are desperately needed to curb the staggering 20% annual mortality rate for patients with endstage renal failure. Recent physiologic and observational studies have highlighted improved outcomes with more frequent hemodialysis. Clinical trials are now needed to establish the efficacy of this promising treatment. Objectives: The Renal Research Institute/University of Western Ontario Clinical Consortium seeks to conduct a randomized controlled trial of 200 patients comparing short daily 6 times per week hemodialysis (target standard Kt/V of 3.5 +/- 0.5 per week) against conventional 3 times per week hemodialysis (target equilibrated KtN of 1.2 +/- 0.1 per session, approximately equal to a standard Kt/V of 2.2 per week). Patients will be followed for 12 to 18 months. The aims of this study include: 1) to determine if the improvements in intermediate cardiovascular, social, nutritional, metabolic, and economic outcomes with daily over conventional hemodialysis, which our consortium has documented in observational studies, persist in a randomized controlled trial, 2) to quantify the adverse events and define potential risks associated with short-daily hemodialysis, and 3) to develop ancillary substudies advancing our knowledge of the physiology of daily hemodialysis. Key design elements to this trial include 1) stratification of the randomization by center and patient preference for in center or home hemodialysis, 2) a run in period of 2 weeks on in center daily hemodialysis, 3) careful standardization of specific co-interventions to provide optimal care and to avoid potential bias associated with the unblinded nature of the trial, and 4) statistical methods which account for missing data due to death and transplantation, and the multiple comparisons on intermediate outcomes used in the trial. Implications: This study will guide the feasibility, sample size and cost of a definitive clinical trial, which examines the effectiveness of daily hemodialysis to prevent death and hospitalization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THERAPY HOMOCYSTEINEMIA

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Principal Investigator & Institution: Eustace, Joseph A.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: (Adapted from the application) End stage renal disease is associated with several complex nutritional problems. Hypoalbuminemia, the strongest predictor of mortality on dialysis, is related to a combination of nutritional, inflammatory and comorbid factors, but the relative importance of these factors has not been prospectively evaluated. Relative vitamin deficiencies, especially that of B6, B12 and folate, also occur. Hyperhomocysteinemia (hyperHcy), a novel cardio-vascular and thrombotic risk factor, is at least partly correctable with folate and vitamin B6 and B12 supplementation but the clinical benefits of this therapy is not established. The projects outlined in this application will allow Dr. Eustace to continue his mentored research into these two major nutritional problems, hypoalbuminemia and hyperHcy. The PI will: (1A) Conduct a longitudinal analysis of risk factors for dialysis-associated hypoalbuminemia focusing on protein intake and inflammation (C-Reactive Protein), using data collected in the CHOICE cohort study. This is a nationally representative cohort of 925 incident dialysis patients in its 5th year of follow-up, headed by Drs. Powe, Klag and Coresh. (1B) Build on a clinical trial, he recently completed, by conducting a two-center, 2 x 2 factorial trial of 280 recently hospitalized hemodialysis patients, with serum albumins of less then 4.0 g/dl, examining in one arm of the trial the efficacy of oral essential amino acids supplements versus placebo at improving serum albumin levels and reducing hospitalization rates and (1C) Use a decision analysis model to compare the costeffectiveness, utility and outcomes of oral supplements versus alternative management strategies, including parenteral nutrition, naso-gastric feeding and anabolic agents. (2A) Compare, in the second arm of the above clinical trial, the efficacy of high versus standard dose folate, B6 & B12 supplementation at reducing all cause cardiovascular endpoints and vascular access thromboses. (2B) Perform a meta-analysis of published trials of the benefit of vitamin therapy on actual patient survival. This combination of observational and experimental research under the mentorship of Drs. Coresh and Klag, combined with didactic course work, in the supportive context of the Welch Center will allow Dr. Eustace to build on his current theoretical knowledge, make the transition into an independent clinical scientist and prepare him for a career investigating the role of nutrition in renal disease. 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 preserve protein mass, thus contributing to the loss of lean body mass. The goals of Dr.

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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 reach these clinical objectives, we propose the following basic research objectives: (1)

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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 “chronic 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 chronic renal failure in the PubMed Central database: •

A micropuncture study of renal phosphate transport in rats with chronic renal failure and secondary hyperparathyroidism. by Bank N, Su WS, Aynedjian HS.; 1978 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372607

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Abnormal Carbohydrate Metabolism in Chronic Renal Failure THE POTENTIAL ROLE OF ACCELERATED GLUCOSE PRODUCTION, INCREASED GLUCONEOGENESIS, AND IMPAIRED GLUCOSE DISPOSAL. by Rubenfeld S, Garber AJ.; 1978 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371732

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Effect of chronic renal failure and hemodialysis on carbohydrate metabolism. by Hampers CL, Soeldner JS, Doak PB, Merrill JP.; 1966 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292856

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Effect of chronic renal failure on Na,K-ATPase alpha 1 and alpha 2 mRNA transcription in rat skeletal muscle. by Bonilla S, Goecke IA, Bozzo S, Alvo M, Michea L, Marusic ET.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295823

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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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Effect of Experimental Chronic Renal Insufficiency on Bone Mineral and Collagen Maturation. by Russell JE, Avioli LV.; 1972 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332989

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Effect of Parathyroid Hormone and Uremia on Peripheral Nerve Calcium and Motor Nerve Conduction Velocity. by Goldstein DA, Chui LA, Massry SG.; 1978 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371740

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Glucose Intolerance in Uremia QUANTIFICATION OF PANCREATIC BETA CELL SENSITIVITY TO GLUCOSE AND TISSUE SENSITIVITY TO INSULIN. by Defronzo RA, Tobin JD, Rowe JW, Andres R.; 1978 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371781

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Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver. by Grossman SB, Yap SH, Shafritz DA.; 1977 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372295

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Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D. by Naveh-Many T, Rahamimov R, Livni N, Silver J.; 1995 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185815

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Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis. by Blum RA, Kohli RK, Harrison NJ, Schentag JJ.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172685

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Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis. by Reitberg DP, Marble DA, Schultz RW, Whall TJ, Schentag JJ.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172210

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Reversal of end-stage renal disease after aortic dissection using renal artery stent: a case report. by Weiss AS, Ludkowski M, Parikh CR.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=416478

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Steady-State Pharmacokinetics of Lamivudine in Human Immunodeficiency VirusInfected Patients with End-Stage Renal Disease Receiving Chronic Dialysis. by Bohjanen PR, Johnson MD, Szczech LA, Wray DW, Petros WP, Miller CR, Hicks CB.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127386

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The Regulation of Skeletal Muscle Alanine and Glutamine Formation and Release in Experimental Chronic Uremia in the Rat SUBSENSITIVITY OF ADENYLATE CYCLASE AND AMINO ACID RELEASE TO EPINEPHRINE AND SEROTONIN. by Garber AJ.; 1978 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371809

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Thyroid Dysfunction in Chronic Renal Failure A STUDY OF THE PITUITARYTHYROID AXIS AND PERIPHERAL TURNOVER KINETICS OF THYROXINE AND TRIIODOTHYRONINE. by Lim VS, Fang VS, Katz AI, Refetoff S.; 1977 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372397

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

A case of normoreninemic aldosterone-producing adenoma associated with chronic renal failure: case report and literature review. Author(s): Koshiyama H, Fujisawa T, Kuwamura N, Nakamura Y, Kanamori H, Oida E, Hara A, Suzuki T, Sasano H. Source: Endocrine. 2003 August; 21(3): 221-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515005

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A retrospective study on efficacy of proton-pump inhibitor-based triple therapy for eradication of Helicobacter pylori in patients with chronic renal failure. Author(s): Mak SK, Loo CK, Wong PN, Lo KY, Tong GM, Lam EK, Wong AK. Source: Singapore Med J. 2003 February; 44(2): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14503780

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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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A trial of objective comparison of quality of life between chronic renal failure patients treated with hemodialysis and renal transplantation. Author(s): Tomasz W, Piotr S. Source: Ann Transplant. 2003; 8(2): 47-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14626576

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Absence of association between organic solvent exposure and risk of chronic renal failure: a nationwide population-based case-control study. Author(s): Fored CM, Nise G, Ejerblad E, Fryzek JP, Lindblad P, McLaughlin JK, Elinder CG, Nyren O. Source: Journal of the American Society of Nephrology : Jasn. 2004 January; 15(1): 180-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694171

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Acquired perforating dermatosis in patients with chronic renal failure: a possible pathogenetic role for fibronectin. Author(s): Bilezikci B, Seckin D, Demirhan B. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 March; 17(2): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705763

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Acute and chronic renal failure. Author(s): Costa J, Crausman RS, Weinberg MS. Source: Journal of the American Podiatric Medical Association. 2004 March-April; 94(2): 168-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15028794

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Acute thyroiditis following parathyroidectomy for secondary hyperparathyroidism in a chronic renal failure patient. Author(s): Lim W, Luxton G, Hutchison B. Source: Internal Medicine Journal. 2003 March; 33(3): 131-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603588

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Adenomatoid tumor of the uterus in a patient with chronic renal failure. Author(s): Bulent Tiras M, Noyan V, Suer O, Bali M, Edali N, Yildirim M. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2000 October; 92(2): 205-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996682

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Adynamic bone and chronic renal failure: an overview. Author(s): Cannata Andia JB. Source: The American Journal of the Medical Sciences. 2000 August; 320(2): 81-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10981480

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Alteration in plasma antioxidant capacities in chronic renal failure and hemodialysis patients: a possible explanation for the increased cardiovascular risk in these patients. Author(s): Clermont G, Lecour S, Lahet J, Siohan P, Vergely C, Chevet D, Rifle G, Rochette L. Source: Cardiovascular Research. 2000 August 18; 47(3): 618-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963735

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Aluminum exposure in chronic renal failure in iberoamerica at the end of the 1990s: overview and perspectives. Author(s): Fernandez-Martin JL, Canteros A, Alles A, Massari P, Cannata-Andia J. Source: The American Journal of the Medical Sciences. 2000 August; 320(2): 96-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10981483

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Anaemia, iron studies and erythropoietin in patients of chronic renal failure. Author(s): Singh NP, Aggarwal L, Singh T, Anuradha S, Kohli R. Source: J Assoc Physicians India. 1999 March; 47(3): 284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999121

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Analysis of mutations in alpha-actinin 4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis. Author(s): Komatsuda A, Wakui H, Maki N, Kigawa A, Goto H, Ohtani H, Hamai K, Oyama Y, Makoto H, Sawada K, Imai H. Source: Renal Failure. 2003 January; 25(1): 87-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617336

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Anemia management and the delay of chronic renal failure progression. Author(s): Rossert J, Fouqueray B, Boffa JJ. Source: Journal of the American Society of Nephrology : Jasn. 2003 July; 14(7 Suppl 2): S173-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819324

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Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: risk of chronic renal failure. End-Stage Renal Disease Study Group. Author(s): Gumprecht J, Zychma MJ, Grzeszczak W, Zukowska-Szczechowska E. Source: Kidney International. 2000 August; 58(2): 513-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10916074

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Anti-Toxoplasma gondii antibodies in haemodialysis patients with chronic renal failure. Author(s): Yazar S, Demirtas F, Yalcin S, Yaman O, Tokgoz B, Utas C, Sahin I. Source: Yonsei Medical Journal. 2003 April 30; 44(2): 288-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728470

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Are plasma S-nitrosothiol levels elevated in chronic renal failure? Author(s): Tsikas D, Frolich JC. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 October; 18(10): 2199; Author Reply: 2199-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679506

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Arteriovenous fistula in chronic renal failure patients: comparison between three different anesthetic techniques. Author(s): Alsalti RA, el-Dawlatly AA, al-Salman M, Jommaa S, Amro K, Dweiri MA, Jasser MT. Source: Middle East J Anesthesiol. 1999 October; 15(3): 305-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10932689

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Assessment of serum osteocalcine level in pre-dialysis patients with chronic renal failure. Author(s): Kumchev EP, Stanchev VL, Yaneva MP, Botushanova AD, Dimitrova RH, Dimitrakov DJ. Source: Folia Med (Plovdiv). 2000; 42(1): 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979170

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Behaviour of urinary dipeptidase in patients with chronic renal failure. Author(s): Fukumura Y, Kera Y, Oshitani S, Ushijima Y, Kobayashi I, Liu Z, Watanabe T, Yamada R, Kikuchi H, Kawazu S, Yabuuchi M. Source: Annals of Clinical Biochemistry. 1999 March; 36 ( Pt 2): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10370741

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Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients. Author(s): Jungers P, Choukroun G, Oualim Z, Robino C, Nguyen AT, Man NK. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 February; 16(2): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158405

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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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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 renal cell carcinoma presenting with chronic renal failure. Author(s): Richter F, Wassel E, Yudd M, Sadeghi-Nejad H. Source: Nephron. 2000 November; 86(3): 354-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096299

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Bilateral trochanteric fractures of the femur in a patient with chronic renal failure. Author(s): Akcali O, Kosay C, Gunal I, Alici E. Source: International Orthopaedics. 2000; 24(3): 179-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10990395

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Blood monocyte phenotypes and soluble endotoxin receptor CD14 in systemic inflammatory diseases and patients with chronic renal failure. Author(s): Scherberich JE, Nockher WA. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 May; 15(5): 5748. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10809793

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Blood pressure and body water distribution in chronic renal failure patients. Author(s): Alvarez-Lara MA, Martin-Malo A, Espinosa M, Rodriguez-Benot A, Aljama P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001; 16 Suppl 1: 947. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11369832

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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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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 body composition in chronic renal failure: effects of growth hormone treatment. Author(s): van der Sluis IM, Boot AM, Nauta J, Hop WC, de Jong MC, Lilien MR, Groothoff JW, van Wijk AE, Pols HA, Hokken-Koelega AC, de Muinck Keizer-Schrama SM. Source: Pediatric Nephrology (Berlin, Germany). 2000 December; 15(3-4): 221-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11149115

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Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Author(s): Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K. Source: Kidney International. 1999 September; 56(3): 1084-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10469378

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Bone mineral density, bone metabolism and body composition of children with chronic renal failure, with and without growth hormone treatment. Author(s): Boot AM, Nauta J, de Jong MC, Groothoff JW, Lilien MR, van Wijk JA, Kistvan Holthe JE, Hokken-Koelega AC, Pols HA, de Muinck Keizer-Schrama SM. Source: Clinical Endocrinology. 1998 November; 49(5): 665-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197084

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Bone scan appearance of renal osteodystrophy in diabetic chronic renal failure patients. Author(s): So Y, Hyun IY, Lee DS, Ahn C, Chung JK, Kim S, Lee MC, Lee JS, Koh CS. Source: Radiat Med. 1998 November-December; 16(6): 417-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929141

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Bone scan findings in patients with chronic renal failure having symptoms related to bone: correlation with parathyroid hormone levels. Author(s): Aktas A, Elahi N. Source: Transplantation Proceedings. 1999 December; 31(8): 3309-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10616488

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Bone, chronic renal failure and GH treatment. Author(s): Lanes R. Source: Clinical Endocrinology. 1999 July; 51(1): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10469481

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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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Ca2+-activated K+ channels mediate relaxation of forearm veins in chronic renal failure. Author(s): Martinez-Leon JB, Segarra G, Medina P, Vila JM, Lluch P, Peiro M, Otero E, Lluch S. Source: Journal of Hypertension. 2003 October; 21(10): 1927-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508200

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Calcitriol increases burst-forming unit-erythroid proliferation in chronic renal failure. A synergistic effect with r-HuEpo. Author(s): Aucella F, Scalzulli RP, Gatta G, Vigilante M, Carella AM, Stallone C. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 95(4): C121-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694273

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Central sensory motor pathways are less affected than peripheral in chronic renal failure. Author(s): Kalita J, Misra UK, Rajani M, Kumar A. Source: Electromyogr Clin Neurophysiol. 2004 January-February; 44(1): 7-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008018

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Changes in body composition of children with chronic renal failure on growth hormone. Author(s): Johnson VL, Wang J, Kaskel FJ, Pierson RN. Source: Pediatric Nephrology (Berlin, Germany). 2000 July; 14(7): 695-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10912545

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Changes in serum insulin-like growth factor binding protein-2, -3, and -6 levels in patients with chronic renal failure following renal transplantation. Author(s): Fukuda I, Hizuka N, Okubo Y, Takano K, Asakawa-Yasumoto K, Shizume K, Demura H, Kimata N, Ishikawa N, Toma H. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 December; 8(6): 481-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10985760

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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 and portal hypertension--is portosystemic shunt indicated? Author(s): Tsimaratos M, Cloarec S, Roquelaure B, Retornaz K, Picon G, Chabrol B, Guys JM, Sarles J, Nivet H. Source: Pediatric Nephrology (Berlin, Germany). 2000 August; 14(8-9): 856-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10955945

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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 in children. Author(s): Derakhshan A, Hashemi GH, Fallahzadeh MH. Source: Transplantation Proceedings. 2003 November; 35(7): 2590-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612030

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Chronic renal failure in Thai children: etiology, cost, and outcome. Author(s): Sumboonnanonda A, Thirakhupt P, Kingwatanakul P, Vongjirad A. Source: J Med Assoc Thai. 2000 August; 83(8): 894-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10998843

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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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Compositional lipoprotein changes and low-density lipoprotein susceptibility to oxidation in chronic renal failure patients with heavy proteinuria. Author(s): Karabina SA, Pappas H, Miltiadous G, Bairaktari E, Christides D, Tselepis A, Elisaf M, Siamopoulos K. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 95(3): C77-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646367

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Contribution of iron deficiency to anemia in chronic renal failure. Author(s): Gupta M, Kannan M, Gupta S, Saxena R. Source: Indian J Pathol Microbiol. 2003 October; 46(4): 563-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025343

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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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Current concepts of anemia management in chronic renal failure: impact of NKFDOQI. Author(s): Eschbach JW. Source: Semin Nephrol. 2000 July; 20(4): 320-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10928333

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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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Dentatorubropallidoluysian atrophy with chronic renal failure in a Japanese family. Author(s): Ono S, Kaneda K, Suzuki M, Tagawa A, Shimizu N. Source: European Neurology. 2002; 47(4): 222-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037436

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Development of chronic renal failure in adult pure mesangial glomerulonephritis. Author(s): Greevska L, Polenakovic M. Source: Renal Failure. 2002 January; 24(1): 59-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11921699

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Development of the idea of chronic renal failure. Author(s): George CR. Source: American Journal of Nephrology. 2002 July; 22(2-3): 231-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097746

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Diabetes mellitus worsens intrarenal hemodynamic abnormalities in nondialyzed patients with chronic renal failure. Author(s): Matsumoto N, Ishimura E, Taniwaki H, Emoto M, Shoji T, Kawagishi T, Inaba M, Nishizawa Y. Source: Nephron. 2000 September; 86(1): 44-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971152

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Dietary therapy in chronic renal failure. (A comedy of errors). Author(s): Maschio G, Oldrizzi L. Source: Journal of Nephrology. 2000 November-December; 13 Suppl 3: S1-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11132024

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Dimethylarginines in chronic renal failure. Author(s): Wahbi N, Dalton RN, Turner C, Denton M, Abbs I, Swaminathan R. Source: Journal of Clinical Pathology. 2001 June; 54(6): 470-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11376022

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Disseminated porokeratosis associated with chronic renal failure: A new type of disseminated porokeratosis? Author(s): Hernandez MH, Lai CH, Mallory SB. Source: Archives of Dermatology. 2000 December; 136(12): 1568-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115182

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Do enzymatic and Jaffe creatinine assays produce comparable results for pre and post dialysis specimens from patients with chronic renal failure? Author(s): Rumbelow BD, Peake MJ, Ehrhardt V. Source: Clin Lab. 2000; 46(11-12): 589-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109507

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Does growth hormone therapy harmonize distorted morphology and body composition in chronic renal failure? Author(s): Zivicnjak M, Franke D, Ehrich JH, Filler G. Source: Pediatric Nephrology (Berlin, Germany). 2000 December; 15(3-4): 229-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11149116

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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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Does treatment modality have an impact on anemia in patients with chronic renal failure? Effect of low- and high-flux biocompatible dialysis. Author(s): Opatrny K Jr, Reischig T, Vienken J, Eiselt J, Vit L, Opatrna S, Sefrna F, Racek J, Brown GS. Source: Artificial Organs. 2002 February; 26(2): 181-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879248

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Dose-dependent effect of an oral adsorbent, AST-120, in patients with early chronic renal failure. Author(s): Yorioka N, Ito T, Masaki T, Ogata S, Asakimori Y, Tanji C, Kyuden Y, Komiya Y, Kumagai J, Taniguchi Y, Kohno N. Source: J Int Med Res. 2002 September-October; 30(5): 467-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12449515

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Doxazosin, but not amlodipine decreases insulin resistance in patients with chronic renal failure: a prospective, randomized-controlled study. Author(s): Yildiz A, Hursit M, Celik AV, Kayacan SM, Yazici H, Akkaya V, Gurol AO, Karsidag K. Source: Clinical Nephrology. 2002 December; 58(6): 405-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508961

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Drug induced pericarditis in a patient with chronic renal failure. Author(s): Bozkurt A, Paydas S. Source: Renal Failure. 2002 September; 24(5): 667-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12380914

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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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Dyspepsia and gastroparesis in chronic renal failure: the role of Helicobacter pylori. Author(s): Schoonjans R, Van VB, Vandamme W, Van HN, Verdievel H, Vanholder R, Lameire N, De VM. Source: Clinical Nephrology. 2002 March; 57(3): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11924751

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Effect of blood purification on plasma levels of intact parathyroid hormone in patients with chronic renal failure. Author(s): Liu J, Liu ZQ, Tao HQ. Source: Di Yi June Yi Da Xue Xue Bao. 2004 February; 24(2): 234-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14965840

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Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Author(s): Haffner D, Schaefer F, Nissel R, Wuhl E, Tonshoff B, Mehls O. Source: The New England Journal of Medicine. 2000 September 28; 343(13): 923-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11006368

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Effect of hemodialysis on the deformability and lipid peroxidation of erythrocytes in chronic renal failure. Author(s): Szikszai Z, Ujhelyi L, Imre SG. Source: Clinical Hemorheology and Microcirculation. 2003; 28(4): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897411

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Effect of the correction of metabolic acidosis on nutritional status in elderly patients with chronic renal failure. Author(s): Verove C, Maisonneuve N, El Azouzi A, Boldron A, Azar R. Source: Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation. 2002 October; 12(4): 224-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382214

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Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized, parallel, double-blind clinical trial. Author(s): Miller HI, Dascalu A, Rassin TA, Wollman Y, Chernichowsky T, Iaina A. Source: American Journal of Nephrology. 2003 March-April; 23(2): 91-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481147

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Effects of chronic renal failure and hemodialysis on the monoethylglycinexylidide liver function test. Author(s): Palatini P, Floreani M, Padrini R, Piccoli P, Bertoli M, Calo L, Orlando R. Source: Clinical Chemistry. 2000 September; 46(9): 1406-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10973873

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Effects of growth hormone in patients with chronic renal failure: experience in children and adults. Author(s): Wuhl E, Schaefer F. Source: Hormone Research. 2002; 58 Suppl 3: 35-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435895

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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 in catabolic adults with chronic renal failure. Author(s): Mehls O, Haas S. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2000 April; 10 Suppl B: S317. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984251

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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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Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure. Author(s): Klein IH, Ligtenberg G, Oey PL, Koomans HA, Blankestijn PJ. Source: Journal of the American Society of Nephrology : Jasn. 2003 February; 14(2): 42530. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538743

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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-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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Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade. Author(s): Goddard J, Johnston NR, Hand MF, Cumming AD, Rabelink TJ, Rankin AJ, Webb DJ. Source: Circulation. 2004 March 9; 109(9): 1186-93. Epub 2004 February 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981006

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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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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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Eruptive vellus hair cyst in patients with chronic renal failure. Author(s): Mieno H, Fujimoto N, Tajima S. Source: Dermatology (Basel, Switzerland). 2004; 208(1): 67-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730241

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Erythropoietin therapy in pre-dialysis patients with chronic renal failure: lack of need for parenteral iron. Author(s): Trivedi HS, Brooks BJ. Source: American Journal of Nephrology. 2003 March-April; 23(2): 78-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481145

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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 associated with chronic renal failure in 121 patients with diffuse proliferative lupus nephritis: a case-control study. Author(s): Arce-Salinas CA, Villa AR, Martinez-Rueda JO, Munoz L, Cardiel MH, Alcocer-Varela J, Alarcon-Segovia D. Source: Lupus. 1995 June; 4(3): 197-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7655489

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Factors predictive of the short- and long-term efficacy of growth hormone treatment in prepubertal children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. Author(s): Haffner D, Wuhl E, Schaefer F, Nissel R, Tonshoff B, Mehls O. Source: Journal of the American Society of Nephrology : Jasn. 1998 October; 9(10): 1899907. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773791

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Fas-dependent fratricidal apoptosis is a mechanism of tubular epithelial cell deletion in chronic renal failure. Author(s): Schelling JR, Nkemere N, Kopp JB, Cleveland RP. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1998 July; 78(7): 813-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9690559

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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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Feeding dysfunction in infants with severe chronic renal failure after long-term nasogastric tube feeding. Author(s): Dello Strologo L, Principato F, Sinibaldi D, Appiani AC, Terzi F, Dartois AM, Rizzoni G. Source: Pediatric Nephrology (Berlin, Germany). 1997 February; 11(1): 84-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035180

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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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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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Fixed low-dose perindopril-indapamide combination in hypertensive patients with chronic renal failure. Author(s): Meyrier A, Dratwa M, Sennesael J, Lachaud-Pettiti V. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1998 September; 11(9): 1087-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9752894

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Fluid balance in patients with chronic renal failure assessed with N-terminal proatrial natriuretic peptide, atrial natriuretic peptide and ultrasonography. Author(s): Metry G, Hall C, Wikstrom B, Kallskog V, Hansell P, Danielson B. Source: Acta Physiologica Scandinavica. 2001 February; 171(2): 117-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11350271

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Foreword: extraskeletal calcifications in patients with chronic renal failure. Author(s): Drueke TB. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 February; 17(2): 330-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11812900

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Four-component model of body composition in chronic renal failure comprising dualenergy X-ray absorptiometry and measurement of total body water by deuterium oxide dilution. Author(s): Woodrow G, Oldroyd B, Turney JH, Davies PS, Day JM, Smith MA. Source: Clinical Science (London, England : 1979). 1996 December; 91(6): 763-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8976813

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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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Free thyroxine concentrations in serum measured by equilibrium dialysis in chronic renal failure. Author(s): Okabayashi T, Takeda K, Kawada M, Kubo Y, Nakamura S, Chikamori K, Terao N, Hashimoto K. Source: Clinical Chemistry. 1996 October; 42(10): 1616-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8855144

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Fulminant pneumonia due to Aeromonas hydrophila in a man with chronic renal failure and liver cirrhosis. Author(s): Murata H, Yoshimoto H, Masuo M, Tokuda H, Kitamura S, Otsuka Y, Miura Y. Source: Intern Med. 2001 February; 40(2): 118-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300143

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Function and metabolism of brain synaptosomes in chronic renal failure. Author(s): Smogorzewski M, Ni Z, Massry SG. Source: Artificial Organs. 1995 August; 19(8): 795-800. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8572998

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Furosemide-albumin complexes in refractory nephrotic syndrome and chronic renal failure. Author(s): Mattana J, Patel A, Ilunga C, Singhal PC. Source: Nephron. 1996; 73(1): 122-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8742982

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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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Generalized atrophic benign epidermolysis bullosa--poor prognosis associated with chronic renal failure. Author(s): Woo HJ, Lee JH, Kim SC, Kim CW, Kim TY. Source: Clinical and Experimental Dermatology. 2000 May; 25(3): 212-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10844498

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Genetic variation of the Apo Al-CIII-AIV gene cluster in hypertriglyceridemic patients with chronic renal failure undergoing hemodialysis. Author(s): Choi GR, Suh SP, Song JW, Kee SJ, Shin JH, Ryang DW. Source: Journal of Korean Medical Science. 2000 June; 15(3): 289-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895970

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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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Grover's disease in patients with chronic renal failure receiving hemodialysis: clinicopathologic review of 4 cases. Author(s): Casanova JM, Pujol RM, Taberner R, Egido R, Fernandez E, Alomar A. Source: Journal of the American Academy of Dermatology. 1999 December; 41(6): 102933. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10570394

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Growth factors and malnutrition in chronic renal failure. Author(s): Fouque DP, Laville M. Source: Adv Nephrol Necker Hosp. 1998; 28: 259-85. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9889994

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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 stimulation tests in chronic renal failure with metabolic acidosis. Author(s): Bircan Z, Kervancioglu M, Soran M, Yildirim I. Source: Acta Paediatr Jpn. 1998 February; 40(1): 70-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9583205

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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 hormone treatment increases circulating lipoprotein(a) in children with chronic renal failure. Author(s): Laron Z, Wang XL, Klinger B, Silbergeld A, Davidovits M, Eisenstein B, Wilcken DE. Source: J Pediatr Endocrinol Metab. 1996 September-October; 9(5): 533-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8961129

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Growth hormone treatment of short children with chronic renal failure before and after renal transplantation: rationale and recent results. Author(s): Mehls O, Wuhl E, Haffner D, Schaefer F, Tonshoff B. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996 September; 11(9): 1747-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8918616

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Growth hormone treatment on chronic renal failure. Author(s): Clarke C. Source: Journal of Paediatrics and Child Health. 1994 December; 30(6): 559. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7865279

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Growth hormone--insulin-like growth factor-I (IGF-I) axis in prepubertal children with chronic renal failure. Author(s): Ferraris J, Pasqualini T, Gutman R, Ramirez J, Fainstein-Day P. Source: J Pediatr Endocrinol Metab. 1997 January-February; 10(1): 19-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9364338

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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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Growth retardation in children with chronic renal failure. Author(s): Kuizon BD, Salusky IB. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1999 October; 14(10): 1680-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10491215

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Head circumference in chronic renal failure from birth. Author(s): Van Dyck M, Proesmans W. Source: Clinical Nephrology. 2001 December; 56(6): S13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11770805

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Hepatic drug metabolism in chronic renal failure. Author(s): Hasanova EA. Source: Seminars in Dialysis. 2004 January-February; 17(1): 69; Author Reply 69-70; Discussion 70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717816

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High doses of mepivacaine for brachial plexus block in patients with end-stage chronic renal failure. A pilot study. Author(s): Rodriguez J, Quintela O, Lopez-Rivadulla M, Barcena M, Diz C, Alvarez J. Source: European Journal of Anaesthesiology. 2001 March; 18(3): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298176

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High frequency audiometry and chronic renal failure. Author(s): Zeigelboim BS, Mangabeira-Albernaz PL, Fukuda Y. Source: Acta Oto-Laryngologica. 2001 January; 121(2): 245-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11349788

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High plasma adenine concentration in chronic renal failure and its relation to erythrocyte ATP. Author(s): Slominska EM, Szolkiewicz M, Smolenski RT, Rutkowski B, Swierczynski J. Source: Nephron. 2002 June; 91(2): 286-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12053067

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High serum enalaprilat in chronic renal failure. Author(s): Elung-Jensen T, Heisterberg J, Kamper AL, Sonne J, Strandgaard S, Larsen NE. Source: J Renin Angiotensin Aldosterone Syst. 2001 December; 2(4): 240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11881130

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Homocysteine in chronic renal failure in relation to renal anemia and to oxidative stress parameters 4-hydroxynonenal and malondialdehyde. Author(s): Carluccio F, Siems W, Stefanelli G, Sommerburg O, Grune T, Riedel E, Hampl H. Source: Clinical Nephrology. 2002 July; 58 Suppl 1: S26-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12227723

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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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Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and cardiac remodeling in chronic renal failure. Author(s): Wolf WC, Yoshida H, Agata J, Chao L, Chao J. Source: Kidney International. 2000 August; 58(2): 730-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10916096

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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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Hyperhomocysteinemia and the risk of thromboembolic phenomenon in patients with chronic renal failure. Author(s): Abdel-Raheem MM, Hebert B, Potti A, Koka VK, Danielson BD. Source: Thrombosis Research. 2002 February 15; 105(4): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031823

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Hypertension in chronic renal failure and ESRD: prevalence, pathophysiology, and outcomes. Author(s): Mailloux LU. Source: Semin Nephrol. 2001 March; 21(2): 146-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11245777

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Hypertensive nephrosclerosis as a relevant cause of chronic renal failure. Author(s): Caetano ER, Zatz R, Saldanha LB, Praxedes JN. Source: Hypertension. 2001 August; 38(2): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509471

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Hypertensive rebound after angiotensin converting enzyme inhibitor withdrawal in diabetic patients with chronic renal failure. Author(s): Piccoli GB, Anania P, Biancone L, Mezza E, Vischi M, Jeantet A, Rabbia C, Savio D, Rossatto D, Gai M, Perin PC, Segoloni GP. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 May; 16(5): 1084-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328932

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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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Hypochronic anemia in chronic renal failure--role of aluminium. Author(s): Agarwal SK. Source: J Assoc Physicians India. 2000 May; 48(5): 549-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11273162

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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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Hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness. Author(s): Jeck N, Reinalter SC, Henne T, Marg W, Mallmann R, Pasel K, Vollmer M, Klaus G, Leonhardt A, Seyberth HW, Konrad M. Source: Pediatrics. 2001 July; 108(1): E5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11433084

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Hypothyroidism mimicking chronic renal failure in reflux nephropathy. Author(s): Bald M, Hauffa BP, Wingen AM. Source: Archives of Disease in Childhood. 2000 September; 83(3): 251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10952648

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IgA nephropathy in a patient with polycythemia vera. Clinical manifestation of chronic renal failure and heavy proteinuria. Author(s): Chung J, Park PG, Song KI. Source: American Journal of Nephrology. 2002 July-August; 22(4): 397-401. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169877

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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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Immunization in children with chronic renal failure. Author(s): Laube GF, Berger C, Goetschel P, Leumann E, Neuhaus TJ. Source: Pediatric Nephrology (Berlin, Germany). 2002 August; 17(8): 638-42. Epub 2002 May 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185473

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Immunoglobulins in chronic renal failure of childhood: effects of dialysis modalities. Author(s): Bouts AH, Davin JC, Krediet RT, van der Weel MB, Schroder CH, Monnens L, Nauta J, Out TA. Source: Kidney International. 2000 August; 58(2): 629-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10916086

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Impact of calcium antagonists on bleeding time in patients with chronic renal failure. Author(s): Hayashi K, Matsuda H, Honda M, Ozawa Y, Tokuyama H, Okubo K, Takamatsu I, Kanda T, Tatematsu S, Homma K, Saruta T. Source: Journal of Human Hypertension. 2002 March; 16(3): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896510

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Impairment of vascular responses to reactive hyperemia and nitric oxide in chronic renal failure. Author(s): Nakanishi T, Ishigami Y, Otaki Y, Izumi M, Hiraoka K, Inoue T, Takamitsu Y. Source: Nephron. 2002; 92(3): 529-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372934

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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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Increased albumin and fibrinogen synthesis rate in patients with chronic renal failure. Author(s): Prinsen BH, Rabelink TJ, Beutler JJ, Kaysen GA, De Boer J, Boer WH, Hagen EC, Berger R, De Sain-Van Der Velden MG. Source: Kidney International. 2003 October; 64(4): 1495-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969171

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Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure. Author(s): Kazama JJ, Shigematsu T, Yano K, Tsuda E, Miura M, Iwasaki Y, Kawaguchi Y, Gejyo F, Kurokawa K, Fukagawa M. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 March; 39(3): 525-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11877571

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Increased incidence of neoplasia in chronic renal failure (20-year experience). Author(s): Cengiz K. Source: International Urology and Nephrology. 2002; 33(1): 121-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12090317

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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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Insulinoma in chronic renal failure: a case report. Author(s): Basu A, Sheehan MT, Thompson GB, Service FJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 4889-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12414845

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Interleukin 18 and interleukin 18 binding protein: possible role in immunosuppression of chronic renal failure. Author(s): Dinarello CA, Novick D, Rubinstein M, Lonnemann G. Source: Blood Purification. 2003; 21(3): 258-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784053

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Interleukin-18, interleukin-18 binding protein and impaired production of interferongamma in chronic renal failure. Author(s): Lonnemann G, Novick D, Rubinstein M, Dinarello CA. Source: Clinical Nephrology. 2003 November; 60(5): 327-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640238

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Intestinal ischemia and peripheral gangrene in a patient with chronic renal failure. Author(s): Rivera-Nieves J, Bamias G, Alfert J, Bickston SJ, Moskaluk CA, Cominelli F. Source: Gastroenterology. 2002 February; 122(2): 495-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11832463

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Intravenous iron dextran treatment in predialysis patients with chronic renal failure. Author(s): Dahdah K, Patrie JT, Bolton WK. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 October; 36(4): 775-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11007680

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Iron and zinc status of patients with chronic renal failure who are not on dialysis. Author(s): Mafra D, Cuppari L, Cozzolino SM. Source: Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation. 2002 January; 12(1): 38-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823992

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Is there a role for protein restriction in the treatment of chronic renal failure? Author(s): Walser M. Source: Blood Purification. 2000; 18(4): 304-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10965072

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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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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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Kidney protection: how to prevent or delay chronic renal failure. Author(s): Steinman TI. Source: Geriatrics. 1996 August; 51(8): 28-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8707068

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Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Author(s): Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Source: Kidney International. 1997 August; 52(2): 495-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9264008

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Kyrle's disease in diabetes mellitus and chronic renal failure. Author(s): Harman M, Aytekin S, Akdeniz S, Derici M. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1998 July; 11(1): 87-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9731978

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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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113

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Late occurrence of chronic renal failure in familial mediterranean fever after 20 years of colchicine treatment. Author(s): Vigneau C, Petrover D, Sraer JD. Source: Annals of Internal Medicine. 2001 December 18; 135(12): 1096. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11747405

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Latex allergy in children with urological malformation and chronic renal failure. Author(s): Sparta G, Kemper MJ, Gerber AC, Goetschel P, Neuhaus TJ. Source: The Journal of Urology. 2004 April; 171(4): 1647-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017256

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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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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 patients undergoing hemodialysis. Author(s): de Gomez Dumm NT, Giammona AM, Touceda LA, Raimondi C. Source: Medicina (B Aires). 2001; 61(2): 142-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11374135

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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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Lipid profile in chronic renal failure at a moderate altitude of 2250 m. Author(s): Gargya, Thakur S, Kapoor D. Source: Indian Journal of Medical Sciences. 1999 November; 53(11): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862268

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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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Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Author(s): Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ. Source: Archives of Internal Medicine. 2000 May 22; 160(10): 1472-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10826460

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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 prevalence of serum HGV-RNA among patients with chronic renal failure without dialysis. Author(s): Cengiz K, Kesim G. Source: Nephron. 2000 March; 84(3): 282-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10720904

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Low protein diets are not needed in chronic renal failure. Author(s): Mehrotra R, Nolph KD. Source: Mineral and Electrolyte Metabolism. 1999 July-December; 25(4-6): 311-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10681658

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Low protein diets delay end-stage renal disease in non diabetic adults with chronic renal failure. Author(s): Fouque D, Wang P, Laville M, Boissel JP. Source: Cochrane Database Syst Rev. 2000; (2): Cd001892. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796832

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115

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Low protein diets for chronic renal failure in non diabetic adults. Author(s): Fouque D, Wang P, Laville M, Boissel JP. Source: Cochrane Database Syst Rev. 2001; (2): Cd001892. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406017

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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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Management of acute and chronic renal failure in the newborn. Author(s): Haycock GB. Source: Seminars in Neonatology : Sn. 2003 August; 8(4): 325-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001136

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Management of anemia of chronic renal failure. Author(s): Singh NP, Anuradha S, Chandrashekhar, Agarwal SK. Source: J Assoc Physicians India. 1999 February; 47(2): 216-23. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999096

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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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Management of the patient with chronic renal failure in the evidence based era. Author(s): Henckes M. Source: Acta Clin Belg. 2002 September-October; 57(5): 257-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534133

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Medical management of secondary hyperparathyroidism in chronic renal failure. Author(s): Goodman WG. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18 Suppl 3: Iii2-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771290

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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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Molecular targets of hyperphosphataemia in chronic renal failure. Author(s): Miyamoto K, Ito M, Segawa H, Kuwahata M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18 Suppl 3: Iii79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771308

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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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Multilevel acute spinal epidural hematoma in a patient with chronic renal failure-case report. Author(s): Ziyal IM, Aydin S, Inci S, Sahin A, Ozgen T. Source: Neurol Med Chir (Tokyo). 2003 August; 43(8): 409-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12968810

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Mycophenolate mofetil and sirolimus as calcineurin inhibitor-free immunosuppression for late cardiac-transplant recipients with chronic renal failure. Author(s): Groetzner J, Meiser B, Landwehr P, Buehse L, Mueller M, Kaczmarek I, Vogeser M, Daebritz S, Ueberfuhr P, Reichart B. Source: Transplantation. 2004 February 27; 77(4): 568-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15084937

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National kidney foundation K/DOQI clinical practice guidelines for nutrition in chronic renal failure. Author(s): Kopple JD. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 January; 37(1 Suppl 2): S66-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158865

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117

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Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalaemia. Author(s): Kiernan MC, Walters RJ, Andersen KV, Taube D, Murray NM, Bostock H. Source: Brain; a Journal of Neurology. 2002 June; 125(Pt 6): 1366-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023325

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Neuroleptic malignant syndrome complicated by massive intestinal bleeding in a patient with chronic renal failure. Author(s): Hayashi H, Kawakatsu S, Watanabe K, Fukasawa T, Otani K. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1225-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452552

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Neurophysiologic parameters and symptoms in chronic renal failure. Author(s): Laaksonen S, Metsarinne K, Voipio-Pulkki LM, Falck B. Source: Muscle & Nerve. 2002 June; 25(6): 884-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115978

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Nitric oxide generation by peripheral blood cells in chronic renal failure. Author(s): Fayed HM, Kame MA, Sultan MM, Mowafy MN, Helmy SM, El-Zoghby MH. Source: British Journal of Biomedical Science. 2002; 59(1): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000182

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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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Novel erythropoiesis-stimulating protein in the management of the anemia of chronic renal failure. Author(s): Maxwell AP. Source: Kidney International. 2002 August; 62(2): 720-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12110039

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Nutrition in children with preterminal chronic renal failure. Myth or important therapeutic aid? Author(s): Wingen AM, Mehls O. Source: Pediatric Nephrology (Berlin, Germany). 2002 February; 17(2): 111-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11875674

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Nutrition in chronic renal failure. Author(s): Bergstrom J. Source: Nefrologia. 2000; 20 Suppl 3: 52-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10835877

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Nutritional support in chronic renal failure: systematic review. Author(s): Zarazaga A, Garcia-De-Lorenzo L, Garcia-Luna PP, Garcia-Peris P, LopezMartinez J, Lorenzo V, Quecedo L, Del Llano J. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 August; 20(4): 291-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11478825

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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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Olfactory function in chronic renal failure. Author(s): Frasnelli JA, Temmel AF, Quint C, Oberbauer R, Hummel T. Source: American Journal of Rhinology. 2002 September-October; 16(5): 275-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422973

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Oral health in children with chronic renal failure. Author(s): Al-Nowaiser A, Roberts GJ, Trompeter RS, Wilson M, Lucas VS. Source: Pediatric Nephrology (Berlin, Germany). 2003 January; 18(1): 39-45. Epub 2002 November 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488989

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Outcome of peritoneal dialysis in cirrhotic patients with chronic renal failure. Author(s): De Vecchi AF, Colucci P, Salerno F, Scalamogna A, Ponticelli C. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 July; 40(1): 161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087574

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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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Oxidative stress and chronic renal failure: markers and management. Author(s): Massy ZA, Nguyen-Khoa T. Source: Journal of Nephrology. 2002 July-August; 15(4): 336-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243361

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Oxidative stress in chronic renal failure as a cardiovascular risk factor. Author(s): Siems W, Quast S, Carluccio F, Wiswedel I, Hirsch D, Augustin W, Hampi H, Riehle M, Sommerburg O. Source: Clinical Nephrology. 2002 July; 58 Suppl 1: S12-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12227720

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Oxidative stress in patients with chronic renal failure: effects of hemodialysis. Author(s): Durak I, Kacmaz M, Elgun S, Ozturk HS. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2004 March-April; 13(2): 84-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755140

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Pathophysiology of gastric acid secretion in patients with chronic renal failure: influence of Helicobacter pylori infection. Author(s): Watanabe H, Hiraishi H, Ishida M, Kazama JJ, Terano A. Source: Journal of Internal Medicine. 2003 November; 254(5): 439-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535965

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Percutaneous coronary interventions in patients with mild to moderate chronic renal failure: to dilate or not to dilate? Author(s): Reinecke H, Schaefer RM. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 November; 18(11): 2218-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551345

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Polymorphonuclear cytosolic Ca(2+) concentration before and after activation in chronic renal failure. Author(s): Caimi G, Canino B, Vaccaro F, Montana M, Carollo C, Oddo G, Lo Presti R. Source: Nephron. 2000 August; 85(4): 371-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10940757

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Predictive risk factors for chronic renal failure in primary high-grade vesico-ureteric reflux. Author(s): Caione P, Villa M, Capozza N, De Gennaro M, Rizzoni G. Source: Bju International. 2004 June; 93(9): 1309-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15180629

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Premature cardiovascular disease in chronic renal failure. Author(s): Baigent C, Burbury K, Wheeler D. Source: Lancet. 2000 July 8; 356(9224): 147-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963260

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Prevalence of biliary lithiasis in a Sicilian population of chronic renal failure patients. Author(s): Li Vecchi M, Soresi M, Cusimano R, Carroccio A, Corrado C, Gioe' A, Montalto G. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 November; 18(11): 2321-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551360

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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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Protein metabolism in chronic renal failure. Author(s): Lim VS. Source: Int J Artif Organs. 2004 January; 27(1): 6-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984177

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Pseudomelanosis duodeni: association with hypertension and chronic renal failure: case report. Author(s): Treeprasertsuk S, Thong-Ngam D, Suwangool P, Kullavanijaya P. Source: J Med Assoc Thai. 2000 August; 83(8): 964-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10998854

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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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QT/corrected QT (QTc) intervals and QT/QTc dispersions in children with chronic renal failure. Author(s): Kocak G, Atalay S, Bakkaloglu S, Ekim M, Tutar HE, Imamoglu A. Source: International Journal of Cardiology. 1999 July 1; 70(1): 63-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10402047

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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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Quantitative computed tomography for spinal bone mineral measurements in chronic renal failure. Author(s): Karantanas AH, Kalef-Ezra JA, Sferopoulos G, Siamopoulos KC. Source: The British Journal of Radiology. 1996 February; 69(818): 132-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8785640

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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 of total homocysteine levels by oral folic acid fails to improve endothelial function in children with chronic renal failure. Author(s): Chan NN, Chan WB, Chan JC. Source: Circulation. 2003 January 7; 107(1): E6-7; Author Reply E6-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12515761

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Relationship between body composition, sex hormones and leptinemia in hemodialyzed patients with chronic renal failure. Author(s): Chudek J, Adamczak M, Kokot F, Karkoszka H, Ignacy W, Klimek D, Wiecek A. Source: Clinical Nephrology. 2002 December; 58(6): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508965

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Renal function in meningomyelocele: risk factors, chronic renal failure, renal replacement therapy and transplantation. Author(s): Muller T, Arbeiter K, Aufricht C. Source: Current Opinion in Urology. 2002 November; 12(6): 479-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409876

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Renal osteodystrophy in chronic renal failure. Author(s): Ho LT, Sprague SM. Source: Semin Nephrol. 2002 November; 22(6): 488-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12430093

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Reticulocyte analysis in systemic lupus erythematosus and chronic renal failure using flow cytometry. Author(s): Butthep P, Jindadamrongwech S, Kaewkethong P, Panyayutho B, Wisedpanichkij R, Bunyaratvej A. Source: Asian Pac J Allergy Immunol. 2000 March; 18(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546054

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Rhinocerebral mucormycosis in a patient with cirrhosis and chronic renal failure. Author(s): Georgopoulou S, Kounougeri E, Katsenos C, Rizos M, Michalopoulos A. Source: Hepatogastroenterology. 2003 May-June; 50(51): 843-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828101

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Rights of chronic renal failure patients undergoing chronic dialysis therapy. Author(s): Andreucci VE, Kerr DN, Kopple JD. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2004 January; 19(1): 30-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671035

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Risk factors for hospital death of patients with end-stage renal disease without previous diagnosis of severe chronic renal failure arriving in an emergency situation at the hospital. Author(s): Abdulkader RC, Zanetta DM, Oliveira GM, Burdmann EA. Source: Renal Failure. 2003 July; 25(4): 631-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911168

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Secondary hyperparathyroidism in children with chronic renal failure: pathogenesis and treatment. Author(s): Sanchez CP. Source: Paediatric Drugs. 2003; 5(11): 763-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580225

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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 vesicoureteral reflux and chronic renal failure: a condition peculiar to male gender? Data from the ItalKid Project. Author(s): Marra G, Oppezzo C, Ardissino G, Dacco V, Testa S, Avolio L, Taioli E, Sereni F; ItalKid Project. Source: The Journal of Pediatrics. 2004 May; 144(5): 677-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127014

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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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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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Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure. Author(s): Di Iorio BR, Minutolo R, De Nicola L, Bellizzi V, Catapano F, Iodice C, Rubino R, Conte G. Source: Kidney International. 2003 November; 64(5): 1822-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531817

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Tentorial and dural calcification with tertiary hyperparathyroidism: a rare entity in chronic renal failure. Author(s): Dorenbeck U, Leingartner T, Bretschneider T, Kramer BK, Feuerbach S. Source: European Radiology. 2002 December; 12 Suppl 3: S11-3. Epub 2002 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522593

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The deceiving image: asymptomatic renal malakoplakia in a patient with chronic renal failure. Author(s): Burdese M, Repetto L, Lasaponara F, Maass J, Bergamo D, Mezza E, Jeantet A, Segoloni GP, Piccoli GB. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 August; 18(8): 1675-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897116

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The effect of chronic renal failure on hepatic drug metabolism and drug disposition. Author(s): Dreisbach AW, Lertora JJ. Source: Seminars in Dialysis. 2003 January-February; 16(1): 45-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535300

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The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron. Author(s): Silverberg DS, Wexler D, Blum M, Tchebiner JZ, Sheps D, Keren G, Schwartz D, Baruch R, Yachnin T, Shaked M, Schwartz I, Steinbruch S, Iaina A. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 January; 18(1): 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480972

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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 growing problem of chronic renal failure after transplantation of a nonrenal organ. Author(s): Magee C, Pascual M. Source: The New England Journal of Medicine. 2003 September 4; 349(10): 994-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954749

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Topical treatment with 22-oxacalcitriol (OCT), a new vitamin D analogue, caused severe hypercalcemia with exacerbation of chronic renal failure in a psoriatic patient with diabetic nephropathy; a case report and analysis of the potential for hypercalcemia. Author(s): Ohigashi S, Tatsuno I, Uchida D, Higurashi M, Hoshimoto S, Seki N, Hashimoto N, Saito Y. Source: Intern Med. 2003 December; 42(12): 1202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714959

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Treating dyslipidemia to slow the progression of chronic renal failure. Author(s): Palmer BF, Alpern RJ. Source: The American Journal of Medicine. 2003 April 1; 114(5): 411-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714133

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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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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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Ultrasonography in chronic renal failure. Author(s): Buturovic-Ponikvar J, Visnar-Perovic A. Source: European Journal of Radiology. 2003 May; 46(2): 115-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714227

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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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Update on vitamin D and its newer analogues: actions and rationale for treatment in chronic renal failure. Author(s): Malluche HH, Mawad H, Koszewski NJ. Source: Kidney International. 2002 August; 62(2): 367-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109997

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Urea percentiles in children with chronic renal failure. Data from the ItalKid project. Author(s): Montini G, Pisanello L, Testa S, Dacco V, Dello Strologo L, Taioli E, Zacchello G, Avolio L, Ciofani A, Claris-Appiani A, Ardissino G; ItalKid Project. Source: Pediatric Nephrology (Berlin, Germany). 2003 March; 18(3): 261-5. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644920

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Urinary deoxypyridinoline excretion for the evaluation of bone turnover in chronic renal failure. Author(s): Coen G, Mantella D, Calabria S, Sardella D, Manni M, Fassino V, D'Anello E, Giustini M, Taggi F. Source: American Journal of Nephrology. 2000 July-August; 20(4): 283-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10970981

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Use of neural networks for dosage individualisation of erythropoietin in patients with secondary anemia to chronic renal failure. Author(s): Martin Guerrero JD, Olivas ES, Valls GC, Serrano Lopez AJ, Perez Ruixo JJ, Torres NV. Source: Computers in Biology and Medicine. 2003 July; 33(4): 361-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791408

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Use of octreotide to treat prolonged sulfonylurea-induced hypoglycemia in a patient with chronic renal failure. Author(s): Nzerue CM, Thomas J, Volcy J, Edeki T. Source: Int J Artif Organs. 2003 January; 26(1): 86-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602474

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Use of vitamin D analogs in chronic renal failure. Author(s): Kim G, Sprague SM. Source: Adv Ren Replace Ther. 2002 July; 9(3): 175-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12203199

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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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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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Vascular calcification in chronic renal failure. Author(s): Goodman WG. Source: Lancet. 2001 October 6; 358(9288): 1115-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11597661

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Vegetative pyoderma gangrenosum in chronic renal failure. Author(s): Goto M, Okamoto O, Fujiwara S, Yanagi T, Komada S, Yokoyama S, Takayasu S. Source: The British Journal of Dermatology. 2002 January; 146(1): 141-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11841382

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Visual acuity disturbances in chronic renal failure. Author(s): Tomazzoli L, De Natale R, Lupo A, Parolini B. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2000; 214(6): 403-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11054000

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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 and its analogs in chronic renal failure. Author(s): Slatopolsky E, Brown AJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1997; 7 Suppl 3: S202-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9536333

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What are the clinical uses of insulin-like growth factor-I in acute and chronic renal failure? Author(s): Hammerman MR. Source: Pediatric Nephrology (Berlin, Germany). 1994 October; 8(5): 544. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7818998

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When to treat dyslipidaemia of patients with chronic renal failure on haemodialysis? A need to define specific guidelines. Author(s): Pedro-Botet J, Senti M, Rubies-Prat J, Pelegri A, Romero R. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996 February; 11(2): 308-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8671784

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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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Which diet for diabetic patients with chronic renal failure? Author(s): Gin H, Rigalleau V, Aparicio M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 November; 14(11): 2577-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534490

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Whole body and regional body composition in patients with chronic renal failure. Author(s): Woodrow G, Oldroyd B, Turney JH, Tompkins L, Brownjohn AM, Smith MA. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996 August; 11(8): 1613-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8856221

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Williams syndrome associated with chronic renal failure and various endocrinological abnormalities. Author(s): Ichinose M, Tojo K, Nakamura K, Matsuda H, Tokudome G, Ohta M, Sakai S, Sakai O. Source: Intern Med. 1996 June; 35(6): 482-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835601

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XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of Frasier syndrome. Author(s): Murray SC. Source: Journal of Pediatric and Adolescent Gynecology. 1998 May; 11(2): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9593608

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

Finding Nutrition Studies on Chronic 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 “chronic renal failure” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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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 chronic 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.

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

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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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

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 chronic 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 Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com

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Minerals Biotin Source: Integrative Medicine Communications; www.drkoop.com Chromium Source: Healthnotes, Inc.; www.healthnotes.com Chromium Source: Prima Communications, Inc.www.personalhealthzone.com

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Vitamin H (Biotin) Source: Integrative Medicine Communications; www.drkoop.com •

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND CHRONIC RENAL FAILURE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to chronic renal failure. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to chronic renal failure and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “chronic renal failure” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to chronic renal failure: •

A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension. Author(s): Petersen LJ, Petersen JR, Talleruphuus U, Moller ML, Ladefoged SD, Mehlsen J, Jensen HA. Source: Clinical Nephrology. 2001 May; 55(5): 375-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11393383

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Acetylcholinesterase activity in chronic renal failure. Author(s): Prall YG, Gambhir KK, Cruz IA, Blassingale J, Ampy FR. Source: Life Sciences. 2000 January 21; 66(9): 835-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10698358

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Anti-lipid peroxidization effect of huangdan on chronic renal failure in rats. Author(s): Zheng J, Hong S, Chen S, Zhang C, Chen J, Zhou S. Source: J Tongji Med Univ. 1997; 17(4): 221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9812784

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Are patients with chronic renal failure (CRF) deficient in Biotin and is regular Biotin supplementation required? Author(s): Jung U, Helbich-Endermann M, Bitsch R, Schneider S, Stein G. Source: Zeitschrift Fur Ernahrungswissenschaft. 1998 December; 37(4): 363-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9894686

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Are supplements of ketoacids and amino acids useful in treating patients with chronic renal failure? Author(s): Mitch WE. Source: Wiener Klinische Wochenschrift. 2000 October 27; 112(20): 863-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11244611

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Aristolochic acids induce chronic renal failure with interstitial fibrosis in saltdepleted rats. Author(s): Debelle FD, Nortier JL, De Prez EG, Garbar CH, Vienne AR, Salmon IJ, Deschodt-Lanckman MM, Vanherweghem JL. Source: Journal of the American Society of Nephrology : Jasn. 2002 February; 13(2): 4316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11805172

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Assessment of thiamin status in chronic renal failure patients, transplant recipients and hemodialysis patients receiving a multivitamin supplementation. Author(s): Frank T, Czeche K, Bitsch R, Stein G. Source: Int J Vitam Nutr Res. 2000 July; 70(4): 159-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10989764

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Atherosclerosis and folic acid supplementation trial in chronic renal failure: Baseline results. Author(s): Zoungas S, Branley P, Kerr PG, Ristevski S, Muske C, Demos L, Atkins RC, Becker G, Fraenkel M, Hutchison BG, Walker R, McNeil JJ, McGrath BP. Source: Nephrology (Carlton). 2004 June; 9(3): 130-141. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15189174

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Autoantibodies against oxidized LDL in chronic renal failure: role of renal function, diet, and lipids. Author(s): Bergesio F, Monzani G, Ciuti R, Cirami C, Martinelli F, Salvadori M, Tosi PL.

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Source: Nephron. 2001 February; 87(2): 127-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11244306 •

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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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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Clinical study on treatment of chronic renal failure with shenshuailing. Author(s): Ju J, Guo Y, Liang Y, Sun S, Yang J, Yang S. Source: J Tradit Chin Med. 2001 June; 21(2): 93-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11498911

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Comparison of a vegetable-based (soya) and an animal-based low-protein diet in predialysis chronic renal failure patients. Author(s): Soroka N, Silverberg DS, Greemland M, Birk Y, Blum M, Peer G, Iaina A. Source: Nephron. 1998; 79(2): 173-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647497

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Comparison of two micronutrient supplements in children with chronic renal failure. Author(s): Coleman JE, Watson AR, Chowdhury S, Thurlby D, Wardell J. Source: Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation. 2002 October; 12(4): 244-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382217

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Dietary treatment of diabetic nephropathy with chronic renal failure. Author(s): Barsotti G, Cupisti A, Barsotti M, Sposini S, Palmieri D, Meola M, Lenti C, Morelli E. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998; 13 Suppl 8: 4952. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9870426

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Does oral folic acid lower total homocysteine levels and improve endothelial function in children with chronic renal failure?

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Author(s): Bennett-Richards K, Kattenhorn M, Donald A, Oakley G, Varghese Z, Rees L, Deanfield JE. Source: Circulation. 2002 April 16; 105(15): 1810-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956124 •

Effect of dietary linoleic acid on the progression of chronic renal failure in rats. Author(s): Gregorio SM, Lemos CC, Caldas ML, Bregman R. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2002 May; 35(5): 573-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011943

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Effect of low-protein diet supplemented with keto acids on progression of disease in patients with chronic renal failure. Author(s): Deniz Ayli M, Ayli M, Ensari C, Mandiroglu F, Allioglu M. Source: Nephron. 2000 March; 84(3): 288-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10720907

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Effect of protein and phosphate restricted and calcium and alphacalcidol supplemented diet on renal and parathyroid functions and protein status in chronic renal failure patients. Author(s): Shah BV. Source: J Assoc Physicians India. 2000 September; 48(9): 936-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11198803

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Effectiveness of green tea tannin on rats with chronic renal failure. Author(s): Yokozawa T, Chung HY, He LQ, Oura H. Source: Bioscience, Biotechnology, and Biochemistry. 1996 June; 60(6): 1000-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8695898

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Effects of dietary fat and polyunsaturated fatty acids in dogs with naturally developing chronic renal failure. Author(s): Bauer JE, Markwell PJ, Rawlings JM, Senior DE. Source: J Am Vet Med Assoc. 1999 December 1; 215(11): 1588-91. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567419

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Effects of fucoidan on chronic renal failure in rats. Author(s): Zhang Q, Li Z, Xu Z, Niu X, Zhang H. Source: Planta Medica. 2003 June; 69(6): 537-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865973

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Effects of Huangdan capsule on plasma cGMP and ANP in rats with chronic renal failure. Author(s): Zheng J, Hong S, Chen S, Chen J, Zhang C. Source: J Tongji Med Univ. 1998; 18(2): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806828

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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): Teplan V, Schuck O, Knotek A, Hajny J, Horackova M, Skibova J, Maly J. Source: Ann Transplant. 2001; 6(1): 47-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11803607

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Enhanced natriuretic response to neutral endopeptidase inhibition in patients with moderate chronic renal failure. Author(s): Lipkin GW, Dawnay AB, Harwood SM, Cattell WR, Raine AE. Source: Kidney International. 1997 September; 52(3): 792-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9291201

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Erythrocyte aminolevulinate dehydratase activity as a lead marker in patients with chronic renal failure. Author(s): Fontanellas A, Navarro S, Moran-Jimenez MJ, Sanchez-Fructuoso AI, Vegh I, Barrientos A, de Salamanca RE. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 July; 40(1): 43-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087560

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European best practice guidelines for the management of anaemia in patients with chronic renal failure. Author(s): Cameron JS. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999; 14 Suppl 2: 615. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10334669

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Evaluation and treatment of chronic renal failure. Author(s): Moudgil A, Bagga A. Source: Indian J Pediatr. 1999 March-April; 66(2): 241-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10798066

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Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure. Author(s): Petersen LJ, Petersen JR, Talleruphuus U, Moller ML, Ladefoged SD, Mehlsen J, Jensen HA.

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Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 July; 14(7): 1673-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435875 •

Heart rate variability and n-3 fatty acids in patients with chronic renal failure--a pilot study. Author(s): Christensen JH, Aaroe J, Knudsen N, Dideriksen K, Kornerup HJ, Dyerberg J, Schmidt EB. Source: Clinical Nephrology. 1998 February; 49(2): 102-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9524780

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High-dose torasemide, given once daily intravenously for one week, in patients with advanced chronic renal failure. Author(s): Boesken WH, Kult J. Source: Clinical Nephrology. 1997 July; 48(1): 22-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9247774

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Incidence of side-effects associated with high-dose ferric gluconate in patients with severe chronic renal failure. Author(s): Bastani B, Jain A, Pandurangan G. Source: Nephrology (Carlton). 2003 February; 8(1): 8-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15012743

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Intensive induction and consolidation chemotherapy in a young woman with acute myeloid leukemia and severe chronic renal failure. Author(s): Hardegger TP, von Rohr A, Tobler A, Fey MF. Source: Annals of Hematology. 1996 May; 72(5): 327-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8645746

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Lipid peroxide levels in chronic renal failure. Author(s): Sharma AK, Arora M, Goyle A, Jain R, Gupta H, Gupta R. Source: J Assoc Physicians India. 1999 March; 47(3): 296-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999124

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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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Lp(a) levels: effects of progressive chronic renal failure and dietary manipulation. Author(s): Monzani G, Bergesio F, Ciuti R, Ciciani AM, Martinelli F, Rosati A, Salvadori M. Source: Journal of Nephrology. 1997 January-February; 10(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9241624

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Muscle potassium content and potassium gluconate supplementation in normokalemic cats with naturally occurring chronic renal failure. Author(s): Theisen SK, DiBartola SP, Radin MJ, Chew DJ, Buffington CA, Dow SW. Source: J Vet Intern Med. 1997 July-August; 11(4): 212-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9298475

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Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure. Author(s): Bennett-Richards KJ, Kattenhorn M, Donald AE, Oakley GR, Varghese Z, Bruckdorfer KR, Deanfield JE, Rees L. Source: Kidney International. 2002 October; 62(4): 1372-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234308

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Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure. Author(s): Samuelsson O, Attman PO, Knight-Gibson C, Larsson R, Mulec H, Wedel H, Weiss L, Alaupovic P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996 November; 11(11): 2237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8941584

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Premature cardiovascular disease and chronic renal failure. Author(s): Wardle EN. Source: Lancet. 2000 September 2; 356(9232): 854-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11022952

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Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure. Author(s): De Nicola L, Bellizzi V, Minutolo R, Andreucci M, Capuano A, Garibotto G, Corso G, Andreucci VE, Cianciaruso B. Source: Kidney International. 1999 August; 56(2): 674-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10432408

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Regular low-intensity aquatic exercise improves cardio-respiratory functional capacity and reduces proteinuria in chronic renal failure patients. Author(s): Pechter U, Maaroos J, Mesikepp S, Veraksits A, Ots M.

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Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 March; 18(3): 624-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584298 •

Renal cell therapy in the treatment of patients with acute and chronic renal failure. Author(s): Humes HD, Weitzel WF, Fissell WH. Source: Blood Purification. 2004; 22(1): 60-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732813

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Role of fermentable carbohydrate supplements with a low-protein diet in the course of chronic renal failure: experimental bases. Author(s): Younes H, Alphonse JC, Behr SR, Demigne C, Remesy C. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1999 April; 33(4): 633-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10196003

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Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. Author(s): Tosi P, Zamagni E, Ronconi S, Benni M, Motta MR, Rizzi S, Tura S, Cavo M. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 July; 14(7): 1310-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914557

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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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Secondary hyperparathyroidism in severe chronic renal failure is corrected by verylow dietary phosphate intake and calcium carbonate supplementation. Author(s): Barsotti G, Cupisti A, Morelli E, Meola M, Cozza V, Barsotti M, Giovannetti S. Source: Nephron. 1998; 79(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647491

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Selenium supplementation on plasma glutathione peroxidase activity in patients with end-stage chronic renal failure. Author(s): Zachara BA, Koterska D, Manitius J, Sadowski L, Dziedziczko A, Salak A, Wasowicz W.

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Source: Biological Trace Element Research. 2004 January; 97(1): 15-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742897 •

Supplements of keto acids in patients with chronic renal failure--more than modulators of nitrogen economy. Author(s): Druml W. Source: Wiener Klinische Wochenschrift. 2001 September 17; 113(17-18): 638-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11603097

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Taste sensitivity is altered in patients with chronic renal failure receiving continuous ambulatory peritoneal dialysis. Author(s): Middleton RA, Allman-Farinelli MA. Source: The Journal of Nutrition. 1999 January; 129(1): 122-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9915887

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The challenge of chronic renal failure in the developing world: possible use of acacia gum. Author(s): Al-Mosawi AJ. Source: Pediatric Nephrology (Berlin, Germany). 2002 May; 17(5): 390-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042902

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The effect of a keto acid supplement on the course of chronic renal failure and nutritional parameters in predialysis patients and patients on regular hemodialysis therapy: the Hungarian Ketosteril Cohort Study. Author(s): Zakar G; Hungarian Ketosteril Cohort Study. Source: Wiener Klinische Wochenschrift. 2001 September 17; 113(17-18): 688-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11603104

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Transient otoacoustic emissions in children with chronic renal failure. Author(s): Samir M, Riad H, Mahgoub M, Awad Z, Kamal N. Source: Clinical Otolaryngology and Allied Sciences. 1998 February; 23(1): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9563674

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Treatment of complications due to peritoneal dialysis for chronic renal failure with traditional Chinese medicine. Author(s): Wei L, Chen B, Ye R, Li H. Source: J Tradit Chin Med. 1999 March; 19(1): 3-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453576

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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.

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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 •

Vegetarian diet alternated with conventional low-protein diet for patients with chronic renal failure. Author(s): Cupisti A, Morelli E, Meola M, Barsotti M, Barsotti G. Source: Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation. 2002 January; 12(1): 32-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823991

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Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin. Author(s): Okada H, Moriwaki K, Kanno Y, Sugahara S, Nakamoto H, Yoshizawa M, Suzuki H. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 September; 15(9): 1410-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10978399

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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

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

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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

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

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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

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

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

The following is a specific Web list relating to chronic 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: •

General Overview Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com High Homocysteine Source: Healthnotes, Inc.; www.healthnotes.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Tuberculosis Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Branched-Chain Amino Acids Source: Healthnotes, Inc.; www.healthnotes.com

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Chitosan Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Inositol Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com L-Tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON CHRONIC RENAL FAILURE Overview In this chapter, we will give you a bibliography on recent dissertations relating to chronic 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 “chronic renal failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on chronic renal failure, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Chronic 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 chronic 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: •

A DOUBLE-EDGED SWORD: PHYSICIANS' VIEWS OF THE END-STAGE RENAL DISEASE PROGRAM. (VOLUMES I AND II) (RENAL DISEASE) by BUFFENBARGER, NANCY LOUISE, PHD from MICHIGAN STATE UNIVERSITY, 1990, 315 pages http://wwwlib.umi.com/dissertations/fullcit/9111570

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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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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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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 5. PATENTS ON CHRONIC 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.8 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 “chronic renal failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on chronic renal failure, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Chronic Renal Failure By performing a patent search focusing on chronic 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. 8Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on chronic 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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Anipamil for the treatment of chronic renal failure Inventor(s): Chan; Laurence (Auroro, CO), Kretzschmar; Rolf (Gruenstadt, DE), Lehmann; Hans D. (Hirschberg, DE), Schrier; Robert W. (Denver, CO) Assignee(s): BASF Aktiengesellschaft (Ludwigshafen, DE) Patent Number: 5,039,709 Date filed: November 30, 1989 Abstract: The use of anipamil and its salts with physiologically tolerated acids for the treatment of chronic renal failure is described. Excerpt(s): The present invention relates to a new use of 1,7-bis(3-methoxyphenyl)-7cyano-3-methylazanonadecane (anipamil). The object of the present invention was to find novel compounds for the treatment of chronic renal failure. In accordance with this

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we have now found that anipamil and its physiologically tolerated salts can be used for the treatment of chronic renal failure. Web site: http://www.delphion.com/details?pn=US05039709__ •

Artificial kidney with moderate exchange rates Inventor(s): Richalley; Gerard (Lyons, FR) Assignee(s): Hospal Industrie (FR) Patent Number: 4,950,395 Date filed: November 27, 1987 Abstract: An artificial kidney capable of operating without a dialysis machine for the treatment of chronic renal failure in discontinuous sessions consisting essentially of:a. a source of a prepackaged dialysis liquid;b. a hemodialyzer with a high permeability membrane continuously traversed by the blood and the dialysis liquid;c. means for collecting the used dialysis liquid and possibly the ultrafiltrate;d. means for measuring the patient's variations in weight; ande. possibly means for injecting a sterile and apyrogenic liquid into the extracorporeal blood circuit.This artificial kidney is particularly intended for operating in a non-hospital environment. Excerpt(s): The present invention relates to a new type of artificial kidney. It concerns more particularly an artificial kidney capable of operating without a dialysis machine, hence requiring only a very straightforward application of reduced material means essentially limited to an exchanger with membranes and some accessories, yet being capable of treating chronic kidney failure in discontinuous sessions. Until now, such artificial kidneys without machines allowing the dialysis to be effected and controlled could only be used for treating acute renal conditions. In fact, these kinds of condition are generally only treated for a few weeks, the natural kidneys then progressively reassuming their function. Thus, the patients can be subjected to artificial purification means operating on a practically continuous basis with very small flows of blood and of the dialysis liquid. These continuous very small flows obviously only require a minimum of means and of supervision. The recent use of high permeability membranes has made it possible to improve the treatment quality but so far, has not modified it in its essential arrangements. To release the patient and to treat him only during a limited weekly period, it is obviously necessary to accelerate the purification rate considerably, in particular by the combined use of high permeability membranes and high circulation rates of the blood and of the dialysis liquid in the hemodialyzer, as well as by the possible application of high pressure differences on either side of the membrane leading to ultrafiltration rates which can be very high and to a partial replacement of the ultrafiltrate (hemodiafiltration). It is clear that such severe treatments require very rigorous permanent controls of many parameters which must be completely mastered and this generally requires the use of ever more sophisticated dialysis machines which are hence expensive and difficult to operate even for staff who must be increasingly highly qualified. Web site: http://www.delphion.com/details?pn=US04950395__

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Composition for alleviating symptoms of uremia in patients Inventor(s): Dickstein; Jack (Huntingdon Valley, PA), Ranganathan; Natarajan (Broomall, PA) Assignee(s): Kibow Biotech Inc. (Philadelphia, PA) Patent Number: 6,706,263 Date filed: April 20, 2000 Abstract: Microencapsulated and/or enteric coated compositions containing a mixture of sorbents with specific adsorption affinities for uremic toxins including ammonia, urea, creatinine, phenols, indoles, and middle molecular weight molecules and a bacterial source which metabolizes urea and ammonia are provided. Also provided are methods of using these compositions to alleviate symptoms of uremia in patients. Excerpt(s): Kidney disease is ranked fourth among the major diseases in the United States afflicting over 20 million Americans. More than 90,000 patients die each year because of kidney diseases. In recent years the number of chronic kidney failure patients has increased about 11 percent annually. About 80,000 Americans on dialysis die of various complications each year and more than 27,000 are on waiting lists for kidney transplants each year with only about 11,000 of these patients receiving transplants. Nearly 250,000 Americans suffer from end stage renal disease (ESRD), which is the final stage in chronic renal failure. Currently hemo- or peritoneal-dialysis and renal transplant are the only treatment modalities. However, the economic costs of these treatment modalities is extremely high. For example, in 1996 in the United States alone, the annual cost of ESRD treatment was over 14 billion dollars. In developing and underdeveloped countries with low health care budgets, ESRD patients are deprived access to such treatments due to their high costs. Accordingly, there is a need for alternative modalities of treatment for uremia. A number of treatment attempts have been based on the use of the bowel as a substitute for kidney function. During a normal digestive process the gastrointestinal tract delivers nutrients and water to the bloodstream and eliminates waste products and undigested materials through the bowel. The intestinal wall regulates absorption of nutrients, electrolytes, water and certain digestive aiding substances such as bile acids. The intestinal wall also acts as a semipermeable membrane allowing small molecules to pass from the intestinal tract into the bloodstream and preventing larger molecules from entering the circulation. Web site: http://www.delphion.com/details?pn=US06706263__

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CRFG-1a, 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: 5,879,908 Date filed: February 9, 1998 Abstract: CRFG-1a polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing CRFG-1a polypeptides and polynucleotides in the design of protocols for the treatment of chronic renal disease, renal ischemia, diabetic nephropathy, acute renal

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failure, Neurodegenerative disease, and Alzheimer's disease, among others, and diagnostic assays for such conditions. Excerpt(s): This application claims the benefit of U.S. provisional application Ser. No. 60/045,203, filed Apr. 30, 1997, which is herein incorporated by reference in its entirety. 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-1a (CRFG-1a). The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. The sequence of CRFG-1a 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. Web site: http://www.delphion.com/details?pn=US05879908__ •

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 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__

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Endothelin antagonists with ether-linked groups Inventor(s): Cheng; Xue-Min (Ann Arbor, MI), Doherty; Annette Marian (Ann Arbor, MI), Patt; William Chester (Chelsea, MI), Repine; Joseph Thomas (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,133,263 Date filed: August 3, 1998 Abstract: Novel nonpeptide endothelin antagonists with ether-linked groups are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating atherosclerosis, restenosis, Raynaud's phenomenon, mild or severe congestive heart failure, cerebral ischemia, cerebral infarction, embolic stroke, cerebral vasospasm, subarachnoid hemorrhage, hemorrhagic stroke, diabetes, gastric ulceration and mucosal damage, ischemnic bowel disease, Chrohn's disease, essential or malignant hypertension, pulmonary hypertension, pulmonary hypertension after bypass, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, male penile erectile dysfunction, cancer, especially malignant hemangicendothelioma or prostate cancer, myocardial infarction or ischemia, acute or chronic renal failure, renal ischemia, radiocontrast-induced nepbrotoxicity, endotoxic, septic, hemorrhagic shock, angina, preeclampsia, asthma, arhythmias, benign prostatic hyperplasia, and elevated levels of endothelin. Excerpt(s): The present invention relates to novel antagonists of endothelin useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. More particularly, the compounds of the present invention are antagonists of endothelin useful in treating elevated levels of endothelin, angina, arrhythmias, asthma, atherosclerosis, benign prostatic hyperplasia, Buerger's Disease, cardiac arrest, cardiogenic shock, cerebral trauma, Chrohn's Disease, congenital heart disease, congestive heart failure (CHF) (mild), congestive heart failure (CHF) (severe), cerebral ischemia, cerebral infarction, cerebral vasospasm, cirrhosis, diabetes, dilated cardiomyopathy, drowning (anoxia), endotoxic shock, gastric mucosal damage, glaucoma, head injury, hemodialysis, hemorrhagic shock, hypertension (essential), hypertension (malignant), hypertension (pulmonary), hypertension (pulmonary, after bypass), hypoglycemia, inflammatory arthritides, ischemic bowel disease, ischemic disease, male penile erectile dysfunction, malignant hemangioendothelioma, myocardial infarction, myocardial ischemia, prenatal asphyxia, postoperative cardiac surgery, prostate cancer, preeclampsia, Raynaud's Phenomenon, renal failure (acute), renal failure (chronic), renal ischemia, restenosis, sepsis syndrome, subarachnoid hemorrhage (acute), surgical operations, status epilepticus, stroke (thromboembolic), stroke (hemorrhagic), Takayasu's arteritis, ulcerative colitis, uremia after hemodialysis, and uremia before hemodialysis. Endothelin-1 (ET-1), a potent vasoconstrictor, is a 21 amino acid bicyclic peptide that was first isolated from cultured porcine aortic endothelial cells. Endothelin-1, is one of a family of structurally similar bicyclic peptides which include: ET-2, ET-3, vasoactive intestinal contractor (VIC), and the sarafotoxins (SRTXs). The distribution of the two cloned receptor subtypes, termed ET.sub.A and ET.sub.B, have been studied extensively (Arai H., et al., Nature, 1990;348:730, Sakurai T., et al., Nature, 1990;348:732). The ET.sub.A, or vascular smooth muscle receptor, is widely distributed in cardiovascular tissues and in certain regions of the brain (Lin H. Y., et al., Proc. Natl. Acad. Sci., 1991;88:3185). The ET.sub.B receptor, originally cloned from rat lung, has been found in rat cerebellum and in endothelial cells. The human ET receptor subtypes have been cloned and expressed (Sakamoto A., et al., Biochem. Biphys. Res. Chem.,

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1991;178:656, Hosoda K., et al., FEBS Lett., 1991;287:23). The ET.sub.A receptor clearly mediates vasoconstriction and there have been a few reports implicating the ET.sub.B receptor in the initial vasodilatory response to ET (Takayanagi R., et al., FEBS Lett., 1991;282:103). However, recent data has shown that the ET.sub.B receptor can also mediate vasoconstriction in some tissue beds (Panek R. L., et al., Biochem. Biophys. Res. Commun., 1992;183(2):566). Web site: http://www.delphion.com/details?pn=US06133263__ •

Method for improving the quality of sleep and treating sleep disorders Inventor(s): Askanazi; Jeffrey (Haworth, NJ), Trimbo; Susan (Evanston, IL) Assignee(s): Clintec Nutrition Co. (Deerfield, IL) Patent Number: 5,278,190 Date filed: April 9, 1992 Abstract: A method for improving the quality of sleep in a chronic renal failure patient is provided. To this end, the present invention provides a method of using branchedchain amino acids as an effective therapy for improving the quality of sleep. The branched-chain amino acid composition can be administered either parenterally or enterally, and can be administered alone or in combination with other nutrients. The composition can be administered during dialysis, intradialytic. Excerpt(s): The present invention relates to a method for the use of branched-chain amino acids to treat sleep disorders. More specifically, the present invention relates to a method for improving sleep quality in a chronic renal failure patient. Sleep disorders may take the form of an abnormal pattern of sleep and increased requirements for medication as well as an overt sleep apnea. Sleep apnea is recognized as a serious and often life threatening abnormality of the breathing pattern. See, Kales, et al, Sleep Disorders: Sleep Apneas and Narcolepsy, Ann. Intern. Med., 106:434-443, 1987. The morbidity of sleep apnea is due to a decrease oxygenation of the arterial blood and carbon dioxide retention secondarily to alveolar hypoventilation. Web site: http://www.delphion.com/details?pn=US05278190__

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Method of retarding the progression of chronic renal failure Inventor(s): Walser; Mackenzie (Ruxton, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 5,175,144 Date filed: November 29, 1988 Abstract: Progression of chronic renal failure can be retarded (slowed or arrested) by administering to humans suffering from such disorder an agent which suppresses the production of glucocorticoids in the human. The agents may be administered alone or in combination with a protein restricted and/or phosphorus restricted diet. Examples of suitable agents which either suppress production of glucocorticoids or block binding to their receptors include sodium valproate, enkephalins, opioids, clonidine, ketoconazole, oxytocin, and mifepristone.

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Excerpt(s): Since the first anecdotal evidence that nutritional therapy may slow the progression of chronic renal failure (see Walser M., "Ketoacids in the Treatment of Uremia," Clinical Nephrology, 3:180-7 (1975)), there has been growing interest in two possibilities: (1) that a common mechanism causes progression of many types of chronic renal failure, and (2) that this process can be slowed or arrested by diet or drugs. Many mechanisms have been postulated, based on experiments in animals and/or clinical observations. Factors proposed to contribute to progression include arterial pressure, and more specifically, glomerular capillary pressure which is reduced by angiotensinconverting enzyme inhibitors; serum calcium times phosphorus product; urinary phosphorus excretion; protein intake itself; hyperuricemia; hypertriglyceridemia; hypercholesterolemia; and hyperoxalemia. As yet, no studies have examined the influence of such factors acting in concert on progression of chronic renal failure. Ketoacid mixtures, administered in conjunction with a low protein, low phosphate diet, have been reported to slow progression in several studies, see Mitch, W. E., et al., "The Effect of a Keto Acid-Amino Acid Supplement to a Restricted Diet on the Progression of Chronic Renal Failure," New England Journal of Medicine, 311:623-9 (1984); Gretz, N., et al., "Low-Protein Diet Supplemented by Ketoacids in Chronic Renal Failure: A Prospective Study," Kidney International, 24, Suppl. 16:S263-7 (1983); and Barsotti, G., et al., "Effects on Renal Function of a Low-Nitrogen Diet Supplemented with Essential Amino Acids and Keto Analogs and of Hemodialysis and Free Protein Supply in Patients with Chronic Renal Failure," Nephron, 27:113-7 (1981), but see Burns, J., et al., "Comparison of the Effects of Ketoacid Analogs and Essential Amino Acids on Nitrogen Homeostasis in Uremic Patients on Moderately Protein-Restricted Diets," American Journal of Clinical Nutrition, 31:1767-1775 (1978). Web site: http://www.delphion.com/details?pn=US05175144__ •

Method of retarding the progression of chronic renal failure Inventor(s): Walser; Mackenzie (Ruxton, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 5,591,736 Date filed: July 3, 1995 Abstract: The progression of chronic renal failure in humans may be retarded by administration of dehydroepiandrosterone (DHEA) in effective amounts. The administration of DHEA is preferably oral at a dose of about 400 to 1600 mg/day. Patients suffering from severe chronic renal failure are also preferably maintained on a protein-restricted diet during DHEA administration. Excerpt(s): The present invention relates to a treatment method for retarding the progression of chronic renal failure in humans. Advanced chronic renal disease in humans is typically associated with multiple endocrine and metabolic abnormalities. Conventional therapy for treating chronic renal failure has focused on proteinrestricted diets in conjunction with administration of ketoacid analogs of amino acids; see U.S. Pat. Nos. 4,100,160, 4,228,099 and 4,352,814, all of Walser, and U.S. Pat. No. 4,752,619 of Walser et al. Another technique for slowing the progression of chronic renal failure is described by Walser in U.S. Pat. No. 5,175,144 and in U.S. application Ser. No. 07/996,757, where the treatment involves administration of ketoconazole or other agent that suppresses glucocorticoid production. Web site: http://www.delphion.com/details?pn=US05591736__

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Method of treating renal disease by administering IGF-I and IGFBP-3 Inventor(s): Higley; Howard R. (Mountain View, CA), Maack; Christopher A. (El Cerrito, CA) Assignee(s): Celtrix Pharmaceuticals, Inc. (Santa Clara, CA) Patent Number: 5,723,441 Date filed: August 31, 1995 Abstract: Treatment with IGF/IGFBP-3 complex increases renal tubular mass and potentiates and/or stimulates kidney function in subjects suffering from acute and chronic renal failure or insufficiency resulting from such disorders as glomerulonephritis, glomerulosclerosis, interstitial nephritis, acute tubular necrosis due to ischemia and drug-induced toxicity, diabetic and autoimmune nephropathies and renal dysfunction due to acute and chronic rejection episodes in post-transplantation patients. Excerpt(s): This invention relates to the treatment of kidney diseases. The method comprises administering a complex comprising insulin-like growth factor (IGF) and an insulin-like growth factor binding protein (IGFBP). Growth factors are polypeptides which stimulate a wide variety of biological responses (e.g., DNA synthesis, cell division, expression of specific genes, etc.) in a defined population of target cells. A variety of growth factors have been identified including transforming growth factor.beta.1 (TGF-.beta.1), TGF-.beta.2, TGF-.beta.3, epidermal growth factor (EGF), plateletderived growth factor (PDGF), fibroblast growth factor (FGF), insulin-like growth factor-I (IGF-I), and IGF-II. Unlike most growth factors, the IGFs are present in substantial quantity in the circulation, but only a very small fraction of this IGF is found in the free form in the circulation or in other body fluids. The overwhelming majority of IGF circulates as part of a non-covalently associated ternary complex composed of IGF-I or IGF-II, an IGF specific binding protein termed IGFBP-3, and a large protein termed the acid labile subunit (ALS). This complex is composed of equimolar amounts of each of the three components. The ALS has no direct IGF binding activity and is thought to only be able to bind a preformed IGF-I/IGFBP-3 complex. The ternary complex of IGF+IGFBP-3+ALS has a molecular weight of approximately 150,000 daltons, and it has been suggested that the function of such a unit in the circulation "may be regarded as a reservoir and a buffer for IGF-I and IGF-II preventing rapid changes of free IGF." See Blum, W. F., et al. (1991), Plasma IGFBP-3 levels as clinical indicators, In: Modern Concepts in Insulin-Like Growth Factors (E. M. Spencer), pages 381-393. Web site: http://www.delphion.com/details?pn=US05723441__

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Nutritional formulation for the treatment of renal disease Inventor(s): Anderson; Pamela A. (Washington Court House, OH), Cipollo; Kent L. (Westerville, OH), Mohacsi; Tivadar G. (Columbus, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 4,957,938 Date filed: June 21, 1989 Abstract: A novel nitritional formulation comprising mixtures of mixed salts formed between branched-chain.alpha.-keto-acids and basic L-amino acid is disclosed which provides optimal nutrition when consumed with a very low protein diet. The

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composition of this invention contains fewer components than other mixtures utilized heretofore while maintaining like proportions of the essential and semi-essential amino acids. The composition of this invention has improved thermal stability and taste and is useful for the nutritional treatment of chronic renal failure (uremia). Excerpt(s): This invention relates to a composition for use in the nutritional treatment of chronic renal failure. More specifically, this invention relates to a mixture comprising four salts formed between branched-chain.alpha.-keto acids and basic L-amino acids; a salt of.alpha.-hydroxy-.gamma.-methylthiobutyrate and three amino acids. The novel composition of this invention can be used in conjunction with a very low protein diet, a vitamin and mineral supplement and other therapeutics for the treatment of renal disease. U.S. Pat. No.4,752,619 discloses and claims a method and composition for the nutritional treatment of chronic renal failure. This reference discloses a mixture of salts which are the reaction product of a basic L-amino acid selected from the group consisting of L-ornithine, L-lysine and L-histidine and a branched-chain.alpha.-keto analog of an essential amino acid selected from the group consisting of.alpha.ketoisocaproate,.alpha.-ketoisovalerate, and.alpha.-keto-.beta.-methylvalerate. The '619 reference claims compositions of no more than five of said salts in recited proportions. The specification and all of the examples recited in the '619 reference relate to mixtures of five salts. The '619 reference does not disclose nor does it contemplate the use of a four salt formulation which provides unexpected product stability while maintaining the equivalent nutritional values. This reference also fails to disclose or anticipate the benefits of the instant four salt composition. These benefits include, but are not limited to lower ingredient costs, increased product stability, reduced quality control, improved odor, improved flavor and improved product homogeneity. European patent application No. 295,166 discloses pharmaceutical compositions for the treatment of uremia which comprises keto-acid salts of ornithine, histidine and lysine. This reference fails to disclose or anticipate that a specific nutritional formulation of four keto salts would evidence enhanced thermal stability and palatability while at the same time supplying the necessary nutritional requirements to the uremic patient. Web site: http://www.delphion.com/details?pn=US04957938__ •

Nutritional supplement for treatment of uremia Inventor(s): Bermudez; Henri (Boulonge Billancourt, FR), Bordat; Claude (Dordives, FR), Walser; Mackenzie (Ruxton, MD) Assignee(s): Synthelabo (Paris, FR), The Johns Hopkins University (Baltimore, MD) Patent Number: 4,752,619 Date filed: December 23, 1985 Abstract: Mixtures of mixed salts formed between branched-chain alpha keto-acids and basic L-amino acids are useful in the nutritional treatment of chronic renal failure (uremia). These compositions contain fewer component salts than other salt mixtures containing like proportions of basic amino acids and keto acids. The compositions can be used in conjunction with a 20-30 g/day mixed quality protein diet and a vitamin and mineral supplement. Excerpt(s): This invention relates to compositions for use in the nutritional treatment of chronic renal failure (uremia). More specifically, this invention relates to mixtures of mixed salts formed between branched-chain alpha-keto acids and basic L-amino acids. The compositions can be used in conjunction with a 20-30 g/day mixed quality protein

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diet, and a vitamin and mineral supplement. Salts of basic L-amino acids, such as Larginine and L-ornithine, and alpha-keto analogs of branched-chain essential amino acids, namely alpha-ketoisocaproate, alpha-ketoisovalerate and alpha-keto-betamethylvalerate are disclosed in U.S. Pat. Nos. 4,228,099, 4,296,127 and 4,320,146, for use in the treatment of hepatic disorders characterized by hyperammonemia and portal systemic encephalopathy, and for treatment of renal failure. Branched-chain keto acids, and alpha-ketoisocaproate in particular, are known to exhibit a nitrogen- or proteinsparing effect in patients with chronic renal failure. That is, branched-chain keto acids reduce urinary nitrogen loss. These keto acids have been used to improve the nitrogen balance in patients suffering from a number of different nitrogen wasting conditions. Web site: http://www.delphion.com/details?pn=US04752619__ •

Treatment of chronic renal failure with imidazole angiotensin-II receptor antagonists Inventor(s): Carini; David J. (Wilmington, DE), Duncia; John Jonas V. (Newark, DE), Wong; Pancras C. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 5,210,079 Date filed: February 7, 1992 Abstract: Substituted imidazoles such as 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5yl)biphenyl-4-yl)methyl]-5-(hydroxy methyl)imidazole and 2-butyl-4-chloro-1-[(2'carboxybiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imi dazole and pharmaceutically acceptable salts thereof are useful for treating chronic renal failure, mediated by angiotensin-II. Excerpt(s): This invention relates to a method of treating chronic renal failure and, in particular, to a method which utilizes imidazole angiotensin-II (AII) receptor antagonists to treat chronic renal failure mediated by angiotensin-II. Angiotensin converting enzyme inhibitors may have beneficial effects over other antihypertensive agents in progressive renal disease of various origins including diabetic nephropathy, essential hypertension and other intrinsic renal diseases (See, e.g., Hypertension: Pathophysiology, Diagnosis, and Management, ed. by J. H. Laragh and B. M. Brenner, vol. 1, pp. 1163-1176, Raven Press, Ltd., New York, 1990; Hypertension: Pathophysiology, Diagnosis, and Management, ed. by J. H. Laragh and B. M. Brenner, vol. 2, pp. 1677-1687, Raven Press, Ltd., New York, 1990). For instance, in partially nephrectomized rats, glomerular capillary hypertension in the remnant kidney is associated with progressive proteinuria, focal glomerular sclerosis, and moderate hypertension. Angiotensin converting enzyme inhibitors, which lower systemic arterial pressure and glomerular capillary pressure, limit the progression of glomerular injury. There are other antihypertensive agents which lower systemic arterial blood pressure to a similar extent, but fail to reduce glomerular capillary pressure. Such agents do not prevent the progression of glomerular injury. It is speculated that in these rats intrarenal generation of angiotensin-II constricts the renal efferent arteriole and causes an increase in glomerular hydraulic pressure. Glomerular hyperfiltration, hyperperfusion and/or hypertension may then initiate and induce glomerular lesions. Thus, blockade of the intrarenal formation of angiotensin-II by angiotensin converting enzyme inhibitors may retard the deterioration of renal failure. Web site: http://www.delphion.com/details?pn=US05210079__

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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 Chronic Renal Failure As of December 2000, U.S. patent applications are open to public viewing.9 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 chronic renal failure: •

Biochemically balanced peritoneal dialysis solutions Inventor(s): Henderson, Lee W.; (Lake Forest, IL), Martis, Leo; (Long Grove, IL) Correspondence: Charles R. Mattenson, ESQ.; Renal Division; Baxter International INC.; One Baxter Parkway; Deerfield; IL; 60015-4633; US Patent Application Number: 20020037329 Date filed: September 17, 2001 Abstract: A peritoneal dialysis solution that is biochemically balanced to correct metabolic acidosis associated with chronic renal failure in a more physiological

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

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manner. The peritoneal dialysis solution has a physiological pH, e.g., pH of 7.0 to 7.4, and contains bicarbonate at a concentration that is found in blood involved in Additionally, the solution contains carbon dioxide at a partial pressure that is similar to partial pressure of carbon dioxide found in the blood capillaries. The peritoneal dialysis solution also contains a weak acid with a pKa of less than 5.0. Excerpt(s): The present invention relates generally to peritoneal dialysis. More specifically, the present invention relates to peritoneal dialysis solutions. It is known to use dialysis to support a patient whose renal function has decreased to the point where the kidneys no longer sufficiently function. Two principal dialysis methods are utilized: hemodialysis; and peritoneal dialysis. In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. A membrane in the machine acts as an artificial kidney for cleansing the blood. Because it is an extracorporeal treatment that requires special machinery, there are certain inherent disadvantages with hemodialysis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for alleviating symptoms of uremia in patients Inventor(s): Dickstein, Jack; (Huntingdon Valley, PA), Ranganathan, Natarajan; (Broomall, PA) Correspondence: Jane Massey Licata; Law Offices OF Jane Massey Licata; 66 E Main Street; Marlton; NJ; 08053; US Patent Application Number: 20010051150 Date filed: April 20, 2000 Abstract: Microencapsulated and/or enteric coated compositions containing a mixture of sorbents with specific adsorption affinities for uremic toxins including ammonia, urea, creatinine, phenols, indoles, and middle molecular weight molecules and a bacterial source which metabolizes urea and ammonia are provided. Also provided are methods of using these compositions to alleviate symptoms of uremia in patients. Excerpt(s): This application claims the benefit of provisional U.S. Application Ser. No. 60/131,774, filed Apr. 30, 1999. Kidney disease is ranked fourth among the major diseases in the United States afflicting over 20 million Americans. More than 90,000 patients die each year because of kidney diseases. In recent years the number of chronic kidney failure patients has increased about 11 percent annually. About 80,000 Americans on dialysis die of various complications each year and more than 27,000 are on waiting lists for kidney transplants each year with only about 11,000 of these patients receiving transplants. Nearly 250,000 Americans suffer from end stage renal disease (ESRD), which is the final stage in chronic renal failure. Currently hemo- or peritonealdialysis and renal transplant are the only treatment modalities. However, the economic costs of these treatment modalities is extremely high. For example, in 1996 in the United States alone, the annual cost of ESRD treatment was over 14 billion dollars. In developing and underdeveloped countries with low health care budgets, ESRD patients are deprived access to such treatments due to their high costs. Accordingly, there is a need for alternative modalities of treatment for uremia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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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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Therapies for chronic renal failure using one or more integrin antagonists Inventor(s): Allen, Andrew; (Lake Forest, IL), Lobb, Roy; (Westwood, MA), Pusey, Charles; (Ealing, GB) Correspondence: Timothy P. Linkkila; Biogen, INC.; 14 Cambridge Center; Cambridge; MA; 02142; US Patent Application Number: 20030007969 Date filed: March 12, 2002 Abstract: The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain integrin antagonists. Excerpt(s): This is a continuation of PCT/US00/25140, filed on Sep. 14, 2000, which claims priority from U.S. provisional application Serial No. 60/153,826 filed on Sep. 14, 1999. The present invention relates generally to methods of treatment for renal disease. In particular, the invention relates to methods of treatment for conditions which place mammals, including humans, in, or at risk of, chronic renal failure. The methods involve the administration of certain integrin antagonists. Many physiological processes require that cells come into close contact with other cells and/or extracellular matrix. Such adhesion events may be required for cell activation, migration (e.g., leukocyte migration), proliferation and differentiation. Cell-cell and cell-matrix interactions are mediated through several families of cell adhesion molecules, one family of which includes the integrins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of prostaglandin (PGE2) receptor 4 (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) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20010041729 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): This application claims the benefit of U.S. Provisional Application No. 60/178,968, filed Jan. 31, 2000. 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,

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PGG, PGH and PGI. It has been well documented that prostaglandins have effects on many of the organs and systems of the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with chronic 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 “chronic 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 chronic renal failure. You can also use this procedure to view pending patent applications concerning chronic 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 CHRONIC RENAL FAILURE Overview This chapter provides bibliographic book references relating to chronic renal failure. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on chronic 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 “chronic 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 chronic renal failure: •

Cardiac Dysfunction in Chronic Uremia Source: Norwell, MA: Kluwer Academic Publishers. 1992. 231 p. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $145 plus shipping and handling. Summary: Cardiac disease is the major cause of death in dialysis patients, accounting for over one-third of deaths. This book focuses on myocardial function and dysfunction in chronic uremia. It is written for practicing and training nephrologists, cardiologists, and internists, and for research workers in the field. The first section comprises five chapters that provide an overview of the burden of illness associated with cardiac disease in endstage renal disease and a review of clinical epidemiological aspects of various cardiac diseases that occur in renal patients. The second section discusses abnormalities of left ventricular contractility and mass, and the factors that predispose to both systolic and

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diastolic disorders. The importance of hypertension, anemia, hyperparathyroidism, hyperlipidemia, and diabetes mellitus is reviewed. The final section concentrates on therapeutics. Data and opinion on management of congestive heart failure, cardiomyopathy, coronary artery disease, hypertension, and arrhythmias are provided. Each chapter includes numerous references and a subject index is appended to the volume. (AA-M). •

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 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).

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Psychosocial Aspects of End-Stage Renal Disease: Issues of Our Times Source: Binghamton, NY: The Haworth Press. 1991. 218 p. Contact: Haworth Press. 10 Alice Street, Binghamton, NY 13904-1580. (607) 722-2493. PRICE: $39.95 plus $3 shipping and handling. ISBN: 1560241497. Summary: In this book, numerous specialists in the field of kidney disease offer insight into the psychosocial aspects of end-stage renal disease. Five sections explore renal disease and the family, the psychosocial dimensions of renal disease, ethical issues in the treatment of renal disease, staff/patient perspectives in the care of renal disease, and renal disease and special patient populations. Within these sections, 20 chapters cover topics including communication between the disciplines in health care provision, families coping with chronic illness, marital and family characteristics, hemodialysis, organ transplantation, dealing with death, illness intrusiveness, coping with the failure of a renal transplant, bioethics, dialysis staff attitudes, patient perceptions, AIDS and end-stage renal disease, and care of the geriatric nephrology patient.

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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.

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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. •

Urea Kinetics in Nutritional Management of Pre-End-Stage Renal Disease, Including Hemodialysis Applications Source: Morgan Hill, CA: Council on Renal Nutrition, Northern California-Northern Nevada. 1993. 30 p. Contact: Available from Council on Renal Nutrition, Northern California-Northern Nevada. c/o Elaine Rodgers, 560 Caprice Court, Morgan Hill, CA 95037. PRICE: $14.95 plus $2.50 postage (as of 1995). ISBN: 1883146518. Summary: This handbook describes the clinical use of urea kinetics in the nutritional management of the pre-ESRD patient. The handbook includes formulas and examples needed to calculate protein requirements and nitrogen balance in this patient population. Topics include the nutritional applications of protein catabolic rate; the calculation of protein catabolic rate; the calculation of creatinine clearance and creatinine generation rate; the use of creatinine data; spot urine; prediction of BUN on a prescribed level of protein intake and known renal function; the differences created by patient size; and practical guidelines for the use of urea kinetics. Also included are a summary of formulas and abbreviations; a clinical nutritional assessment summary; a urea kinetics summary worksheet; guidelines for determining lean body weight; and urine collection instructions. The booklet concludes with a brief glossary. 14 references.

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Clinical Guide to Nutrition Care in End-Stage Renal Disease. 2nd ed Source: Chicago, IL: American Dietetic Association. 1994. 255 p. 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 manual provides guidelines for the clinical nutrition care of patients with end-stage renal disease (ESRD). Designed for renal dietitians, the manual contains 14 chapters and 11 appendices covering topics including normal and diseased kidney anatomy and function; nutrition assessment in chronic renal failure; dietary treatment in the early stages of chronic renal failure; nutrition management of adult hemodialysis and peritoneal dialysis patients; the nutrition management of the adult renal transplant patient; nutrition management of the patient with diabetes and renal disease; nutrition recommendations for infants, children and adolescents with ESRD; enteral nutrition in end-stage renal disease; parenteral nutrition for the patient with renal failure; medications commonly prescribed in chronic renal failure; renal osteodystrophy;

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attaining nutrition goals for hyperlipidemic and obese renal patients; nutrition management of the patient with urolithiasis; nutrition care of the hospitalized patient with renal failure; helpful hints for common patient problems; the management of anemia in ESRD; pregnancy and dialysis; hyperdietism; forms and documents; disaster diet information for hemodialysis patients; guidelines for estimating renal dietitian staffing levels, and funding for ESRD nutrition services. One of the appendices lists professional organizations for renal dietitians and another provides a medication and manufacturer reference index. The volume concludes with a subject index. •

Atlas of Diseases of the Kidney. Volume 5: Dialysis as Treatment of End-Stage Renal Disease/Transplantation as Treatment of End-Stage Renal Disease Source: Philadelphia, PA: Current Medicine, Inc. 1999. [270 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: 0632043911. Summary: This volume is the last in a series of five that make up the Atlas of Diseases of the Kidney, a set that offers educational images including colored photographs, schematics, tables, and algorithms. In Volume 5, 7 chapters consider dialysis as treatment of end stage renal disease (ESRD), and 10 chapters cover transplantation as treatment of ESRD. The first section is organized to provide a systematic overview of dialytic procedures. The first chapter discusses the principles of dialysis and the mechanics of practical therapy. One essential feature of the dialysis procedure is the composition of dialysate, which is discussed in detail in the second chapter. Newer dialytic therapies such as high efficiency dialysis and continuous dialysis therapy techniques are discussed next; these treatments have resulted in shorter dialysis times in patients with chronic renal failure and have been useful in the management of complicated acute renal failure (ARF) patients. Other chapters cover peritoneal dialysis, problems with arteriovenous fistula access, dialysis prescription and methods of measuring urea, and several complications that afflict patients with renal failure who are on dialysis, including blood pressure regulation and chronic inflammation. The second section details transplantation, including several chapters on the evaluation of donors and recipients, including their posttransplant complications. One chapter addresses the technical aspects of transplantation, shows the operation, and provides the basis for making the diagnostic and therapeutic decisions necessary when a patient develops postoperative renal dysfunction. Other chapters cover combined kidney and pancreas transplantation, tissue typing and organ sharing, immunosuppressive drugs, and the management of renal transplant rejection. Finally, the special needs of pediatric transplantation and the intriguing area of recurrent disease are covered. Each chapter features a detailed introduction and lengthy captions for each of the illustrations and diagrams offered. A subject index for Volume 5 and a section of full color plates concludes the book.

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

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books. When searching for “chronic renal failure” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “chronic renal failure” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “chronic renal failure” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

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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Animal Models in Chronic Renal Failure (Contributions to Nephrology, Vol 60) by N. Gretz, M. Strauch; ISBN: 380554619X; http://www.amazon.com/exec/obidos/ASIN/380554619X/icongroupinterna

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Bone densitometry patients with end-stage renal disease (SuDoc HE 20.6512/7:996/8) by U.S. Dept of Health and Human Services; ISBN: B00010SRZO; http://www.amazon.com/exec/obidos/ASIN/B00010SRZO/icongroupinterna

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Cardiac Dysfunction in Chronic Uremia (Topics in Renal Medicine, Vol 10) by Patrick S. Parfrey, John D. Harnett; ISBN: 0792313518; http://www.amazon.com/exec/obidos/ASIN/0792313518/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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Growth and Endocrine Changes in Children and Adolescents With Chronic Renal Failure (Pediatric and Adolescent Endocrinology, Vol 20) by K. Scharer; ISBN: 3805549903; http://www.amazon.com/exec/obidos/ASIN/3805549903/icongroupinterna

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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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Laboratory tests in end-stage renal disease patients undergoing dialysis (SuDoc HE 20.6512/7:994/2) by Ira Green; ISBN: B00010LRW4; http://www.amazon.com/exec/obidos/ASIN/B00010LRW4/icongroupinterna

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Low Protein Diet and Progression of Chronic Renal Failure (Contributions to Nephrology, Vol 53) by M. Strauch, et al; ISBN: 3805543646; http://www.amazon.com/exec/obidos/ASIN/3805543646/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

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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; ISBN: 3805551894; http://www.amazon.com/exec/obidos/ASIN/3805551894/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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Prevention of Progressive Chronic Renal Failure (Oxford Monographs on Clinical Nephrology, No 1) by A. Meguid El Nahas, et al; ISBN: 0192622374; http://www.amazon.com/exec/obidos/ASIN/0192622374/icongroupinterna

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Rehabilitation in chronic renal failure (Rehabilitation medicine library); ISBN: 0683015788; http://www.amazon.com/exec/obidos/ASIN/0683015788/icongroupinterna

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The Misfortunes of Others: End-Stage Renal Disease in the United Kingdom (Studies in Philosophy and Health Policy) by Thomas Halper; ISBN: 0521350476; http://www.amazon.com/exec/obidos/ASIN/0521350476/icongroupinterna

Chapters on Chronic Renal Failure In order to find chapters that specifically relate to chronic renal failure, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and chronic 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 “chronic renal failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on chronic renal failure: •

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 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.

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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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Management of End-stage Renal Disease in Diabetes Source: in Johnson, R.J. and Feehally, J. Comprehensive Clinical Nephrology. 2nd ed. Orlando, FL: Mosby, Inc. 2003. p. 451-462. 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: Diabetic nephropathy (kidney disease associated with diabetes mellitus) is the single largest cause of end stage renal (kidney) disease (ESRD) in American and European adults, accounting for over one third of all patients beginning renal replacement therapy (dialysis and transplantation). Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (protein in the urine). Patients invariably develop associated hypertension (high blood pressure), a progressive increase in proteinuria, and a predictable and relentless decline in glomerular filtration rate (GFR, a measure of kidney function). This chapter on the management of ESRD in diabetes is from a comprehensive textbook that covers every clinical condition encountered in nephrology (the study of kidney disease). The author of this chapter covers the incidence of ESRD resulting from diabetic nephropathy, predialysis care for the person with diabetes, microvascular complications, macrovascular complications, blood pressure control, infection, metabolic complications, psychological and social care, peritoneal dialysis versus hemodialysis, survival and causes of death in people with diabetes and ESRD, the outcome of dialysis, hospitalization and technique survival, and kidney transplantation in patients with diabetes. The chapter is clinically focused and extensively illustrated in full color. 10 figures. 1 table. 34 references.

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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.

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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. •

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. 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,

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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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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

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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. •

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. 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.

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Options for Patients with End-Stage Renal Disease Source: in Danovitch, G.M., ed. Handbook of Kidney Transplantation. 3rd ed. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 1-16. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2365. PRICE: $42.00 plus shipping and handling. ISBN: 0781720664. Summary: This chapter is from a handbook of kidney transplantation that provides practical information on therapy, patient monitoring, and patient care management. In this chapter, the authors outline options for patients with end stage renal disease (ESRD). Despite advances in knowledge and skill in treating chronic renal failure (CRF), patients with ESRD often remain unwell even when maintained by regular dialysis. Constitutional symptoms of fatigue and malaise persist despite the dramatic improvement that followed the introduction of erythropoietin for the management of the anemia of CRF. Progressive cardiovascular disease (CVD), peripheral and autonomic neuropathy, bone disease, and sexual dysfunction are common even in patients who receive adequate amounts of dialysis. For most patients with ESRD, kidney transplantation offers the greatest potential for restoring a healthy, productive life. However, practitioners of kidney transplantation must consider the clinical effects

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of ESRD on the overall health of renal transplantation candidates when this therapeutic option is first considered. The authors consider the demographics of the ESRD population, then outline each of the treatment options, including hemodialysis, peritoneal dialysis, and transplantation. The authors focus on issues of patient selection and when to initiate ESRD therapy. 5 figures. 2 tables. 13 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 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

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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. •

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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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

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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). •

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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Influences of Diet on the Progression of Chronic Renal Insufficiency Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 317-340. 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 influences of diet on the progression of chronic renal insufficiency is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The author notes that, in spite of intensive investigation, the mechanisms by which a low-protein diet could change the rate of loss of renal function have not been fully elucidated. In addition, the underlying mechanisms causing progressive loss of renal function have not been unequivocally identified, even in experimental animals. The author provides information designed to help readers make a rational decision about whether to implement nutritional therapy for a patient with progressive loss of renal function. Topics covered include the nutritional adequacy of restricted diets; monitoring changes in renal function, including serum creatinine; low protein diets used to slow progress; assessment of dietary compliance; urea generation and protein nitrogen appearance; diabetic nephropathy and dietary protein restriction; supplemented low protein diets; and the Modification of Diet in Renal Disease (MDRD) Study. The author concludes that compliance with dietary protein restriction can be assessed reliably using available methods, and dietary regimens do not cause malnutrition if effort is made to ensure the nutritional adequacy of the diet actually ingested. Because there is evidence that dietary manipulation can slow progression in some patients, a low protein diet should be instituted in patients

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who have documented progressive renal insufficiency in spite of adequate treatment of hypertension. 4 figures. 1 table. 83 references. (AA-M). •

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: [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.

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Restricted Diets and Slowing the Progression of Chronic Renal Insufficiency Source: in Mitch, W.E. and Klahr, S., eds. Nutrition and the Kidney. 2nd ed. Boston, MA: Little, Brown and Company. 1993. p. 243-262. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail:

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[email protected]. Website: http://www.lrpub.com. PRICE: $94.95. ISBN: 0316575003. Summary: This chapter, from a book about nutritional requirements during kidney disease, discusses the use of restricted diets and slowing the progression of chronic renal insufficiency. The author notes that the effectiveness of a low-protein diet in slowing progression has not been proved in a multicenter trial; information in the chapter is provided to help physicians make a rational decision about whether or not to implement nutritional therapy for a patient with progressive loss of renal function. Topics include the rationale for dietary restriction, monitoring changes in renal function; serum creatinine; low-protein diets used to slow progression; assessment of dietary compliance, urea generation and the protein catabolic rate; and dietary protein restriction and progression of renal insufficiency. 3 figures. 2 tables. 57 references. •

Conservative Management of Chronic Renal Failure Source: in Kher, K.K.; Makker, S.P., eds. Clinical Pediatric Nephrology. New York, NY: McGraw-Hill. 1992. p. 543-558. Contact: Available from McGraw-Hill, Inc. P.O. Box 545, Blacklick, OH 43004. (800) 2624729. PRICE: $85.00 plus $3.00 shipping and handling. ISBN: 0070345430. Summary: This chapter, from a book on clinical pediatric nephrology, discusses the conservative management of chronic renal failure (CRF). The author notes that management strategy is aimed at minimizing the metabolic side effects of uremia, maintaining a normal fluid and electrolyte balance, preventing long-term complications, and treating complications that already may have developed. Topics include nutrition; fluid intake; sodium and potassium intake; prevention of renal osteodystrophy; correction of acidosis; treatment of anemia; treatment of hypertension; providing psychosocial support; preparing for dialysis and transplantation; and other management issues, including aluminum toxicity, growth, reproductive functions, and uremic bleeding. A final section briefly discusses financial planning for end-stage renal disease. Appended to the chapter is a commentary by Russel W. Chesney about the management of renal osteodystrophy. 3 figures. 5 tables. 36 references.

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Chronic Renal Failure and Dialysis Source: in Little, J.W.; Falace, D.A. Dental Management of the Medically Compromised Patient. 4th ed. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 248-257. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail: [email protected]. PRICE: $44.95. ISBN: 0801668379. Summary: This chapter, from a guide to the dental management of medically compromised patients, covers the effects of renal failure and dialysis. The authors discuss the basic pathophysiology, clinical findings, medical management, and dental management of patients with renal failure. The dental management is discussed for patients under conservative care and those undergoing hemodialysis; treatment planning modifications and oral complications are considered. The goal of dental care for patients receiving conservative treatment for ESRD is to restore the mouth to the healthiest condition possible and to eliminate possible sources of infection. Several oral changes are seen with chronic renal failure, including pallor of the oral mucosa secondary to anemia, diminished salivary flow, stomatitis, and dental changes. Problems associated with hemodialysis include concerns about infection, hepatitis virus

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infection, problems with drugs that are metabolized primarily by the kidney or that are nephrotoxic, and abnormal bleeding. The best time for dental treatment is the day following hemodialysis. 8 figures. 2 tables. 9 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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Etiologies and Indicators of Powerlessness in Persons with End-Stage Renal Disease Source: in Miller, J.F., ed. Coping with Chronic Illness: Overcoming Powerlessness. 2nd ed. Philadelphia, PA: F.A. Davis Company. 1992. p. 163-178. Contact: Available from F.A. Davis Company. 1915 Arch Street, Philadelphia, PA 191039954. (800) 323-3555 or (215) 440-3001. PRICE: $26.95 (as of 1996). ISBN: 0803661924. Summary: This chapter, from a nursing text on coping with chronic illness, discusses the physiologic, psychologic, role disturbance, and life change stressors that people with end-stage renal disease (ESRD) may face. The author presents a summarized review of literature of these stressors and reports observations of powerlessness in patients with chronic renal failure (CRF). The author makes conclusions about patient responses to powerlessness in order to help nurses identify behavioral indicators of the nursing diagnostic category of powerlessness in other chronically ill patients. The author focuses on strategies to help prevent and alleviate feelings of powerlessness in patients with chronic illness. 1 figure. 2 tables. 39 references. (AA-M).

•

Overview of the Management of Anemia in End-Stage Renal Disease Source: in American Dietetic Association. Clinical Guide to Nutrition Care in End-Stage Renal Disease. Chicago, IL: American Dietetic Association. 1994. p. 195-197. 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 is an appendix from a manual that provides guidelines for the clinical nutrition care of patients with end-stage renal disease (ESRD). In it the author provides an overview of the management of anemia in ESRD. Topics include the use of recombinant human erythropoietin (rHuEPO) in all modes of ESRD treatment;

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administration of rHuEPO in hemodialysis and peritoneal dialysis patients; how rHuEPO works to stimulate red blood cell production; monitoring of patients on rHuEPO; maintaining adequate iron status with iron supplementation; and evaluating overall nutritional and biochemical parameters of patients receiving rHuEPO. 14 references. •

Nutrition Management of Chronic Renal Failure Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 535-553. 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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Adequacy of Treatment for End-Stage Renal Disease in the United States Source: in Schrier, R.W., et al., eds. Advances in Internal Medicine. Vol 41. St. Louis, MO: Mosby-Year Book, Inc. 1996. p. 323-363. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail: [email protected]. PRICE: $72.95. ISBN: 0815183143. ISSN: 00652822. Summary: Whatever the cause of chronic or irreversible renal failure, when damage is complete, appearance of the more severe of the uremic symptoms permits the diagnosis of end-stage renal disease (ESRD). This chapter, from a yearbook of advances in internal medicine, considers the adequacy of treatment for ESRD in the United States. Topics include the origin of treatments for ESRD and the historical perspective of the development of different types of dialysis; expanding availability of treatments for ESRD, including the federally supported hemodialysis program; management of the ESRD program; selection and acceptance to therapy for ESRD; ESRD treatments, including transplantation, hemodialysis, and peritoneal dialysis; factors influencing the choice of modality; the prescription for dialysis adequacy; medical management, including access to blood or peritoneum, anemia, bone disease, and transplant care; mortality and morbidity considerations; and deficiencies in quality of ESRD care, including mortality in international comparisons, and contributory factors such as comparative treatment efficiency, patient selection, the effect of capped reimbursement rates, shortcuts to reuse, and medical management. In the final section, the authors

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present suggestions for improving the medical management of patients with ESRD. They discuss pre-ESRD care, increasing the dialysis dose, the role of the hemodialyzer membrane, improving access to transplantation, improving patient care, the role for the government, resolving patient-professional discord, and data collection and analysis. The authors conclude that the U.S. experiences with ESRD can be used as a model for American health care. 5 tables. 94 references.

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CHAPTER 7. MULTIMEDIA ON CHRONIC RENAL FAILURE Overview In this chapter, we show you how to keep current on multimedia sources of information on chronic 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.

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 “chronic renal failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on chronic renal failure: •

Diet and the Retardation of the Progression of Chronic Renal Failure Source: Bethlehem, PA: St. Luke's Hospital. 1991. 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 CHRONIC RENAL FAILURE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover chronic renal failure.

News Services and Press Releases One of the simplest ways of tracking press releases on chronic 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 “chronic 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 chronic 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 “chronic renal failure” (or synonyms). The following was recently listed in this archive for chronic renal failure: •

High phenylacetic acid in chronic renal failure may lead to vascular disease Source: Reuters Medical News Date: July 18, 2003

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•

Nocturnal hemodialysis effective for sleep apnea in chronic renal failure patients Source: Reuters Medical News Date: January 10, 2001

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Short-course iron treatment cost-effective in chronic renal failure patients Source: Reuters Industry Breifing Date: October 24, 2000 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. 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 “chronic 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 “chronic renal failure” (or synonyms). If you know the name of a company that is relevant to chronic 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/.

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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 “chronic renal failure” (or synonyms).

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 “chronic 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 chronic 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.

•

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.

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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. •

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.

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Academic Periodicals covering Chronic Renal Failure Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to chronic renal failure. In addition to these sources, you can search for articles covering chronic 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.” 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 chronic 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 non-profit 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 chronic 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.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to chronic renal failure: Darbepoetin alfa •

Systemic - U.S. Brands: Aranesp http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500331.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.

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 chronic 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 “chronic 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

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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 chronic renal failure: •

Somatropin for Injection (trade name: Nutropin) http://www.rarediseases.org/nord/search/nodd_full?code=100

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 Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

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

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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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

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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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.11 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:12 •

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

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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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

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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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

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

11

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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “chronic 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 52973 488 999 111 253 54824

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “chronic renal failure” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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.

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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 chronic 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 Internetbased 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 chronic 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 chronic 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 “chronic renal failure”:

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African-American Health http://www.nlm.nih.gov/medlineplus/africanamericanhealth.html 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 Transplantation http://www.nlm.nih.gov/medlineplus/kidneytransplantation.html

Within the health topic page dedicated to chronic renal failure, the following was listed: •

Diagnosis/Symptoms Medical Tests of Kidney Function Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/kidneytests/index.htm

•

Treatment Kidney Failure: Choosing a Treatment That's Right for You Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/choosingtreatment/index.htm Kidney Transplant Source: National Kidney Foundation http://www.kidney.org/atoz/pdf/kidney_trans.pdf Treatment Methods for Kidney Failure: Transplantation Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/transplant/index.htm

•

Coping Coping Effectively: A Guide for Patients and Their Families Source: National Kidney Foundation http://www.kidney.org/atoz/pdf/coping.pdf

•

Children School & Family Problems of Children with Kidney Failure Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/childkidneydiseases/school_famil y_problems/index.htm 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

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thods/index.htm When Your Child Has a Chronic Kidney Disease Source: Nemours Foundation http://kidshealth.org/parent/medical/kidney/chronic_kidney_disease.html •

Latest News Functioning Kidneys Grown in Rats Source: 06/28/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_18612 .html More Intensive Dialysis Helps Women More Than Men Source: 06/21/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_18482 .html National NIH Initiative Aims to Reduce Kidney Failure Among African Americans Source: 06/15/2004, National Institute of Diabetes and Digestive and Kidney Diseases http://www.nih.gov/news/pr/jun2004/niddk-15.htm Renal Physicians and NIH Release Web Tool to Coordinate Care for Kidney Patients Source: 06/08/2004, National Institute of Diabetes and Digestive and Kidney Diseases http://www.nih.gov/news/pr/jun2004/niddk-08.htm Transplant Ups Survival When Kids' Kidneys Fail Source: 06/28/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_18619 .html

•

Law and Policy Medicare Coverage of Kidney Dialysis and Kidney Transplant Services Source: Dept. of Health and Human Services http://www.medicare.gov/Publications/Pubs/pdf/esrdCoverage.pdf

•

Organizations American Association of Kidney Patients http://www.aakp.org/ American Kidney Fund http://www.akfinc.org/ 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 FDA Approves First in a New Class of Drugs to Treat Hyperparathyroidism Associated with Renal Failure and in Patients with Parathyroid Cancer Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01282.html Timing of Evaluation by Specialists for Patients with Chronic Kidney Disease Source: American College of Physicians http://www.annals.org/cgi/content/full/137/6/I-24

•

Statistics End Stage Renal Disease in the United States Source: National Kidney Foundation http://www.kidney.org/general/news/factsheet.cfm?id=38 Kidney and Urologic Disease Statistics for the United States Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.htm Kidney Center Data Profile Source: Organ Procurement and Transplantation Network http://www.optn.org/organDatasource/stateData.asp?type=state&mqsd=1&displ ay=Kidney Kidney Disease Facts & Statistics: New Cases Statistics Source: American Society of Nephrology http://www.asn-online.org/facts_and_statistics/newcases.aspx Kidney Disease Facts & Statistics: Prevalence Source: American Society of Nephrology http://www.asn-online.org/facts_and_statistics/prevalence.aspx

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 chronic renal failure. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s

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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: •

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.

•

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.

•

Chronic 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 54, p. 54.1-54.13. 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 chronic renal failure (CRF) 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. 2 tables. 18 references.

208

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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 close cooperation between patient and doctor. EPO can be an important adjunct to successfully living with chronic renal 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: •

Kidney Disease of Diabetes Summary: This consumer fact sheet discusses diabetes and end-stage renal disease (ESRD) and the treatments and therapies involved. Source: National Kidney and Urologic Diseases Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Disease http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2085 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 chronic 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. 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

Patient Resources

•

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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to chronic renal failure. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with chronic 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 chronic 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 “chronic 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 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

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your search to “Organizations” and “chronic 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 “chronic 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 “chronic 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.21

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

21

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)22: •

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/

22

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

•

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

•

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

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

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

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

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

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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/

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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

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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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

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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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

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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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

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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

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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/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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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

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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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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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/

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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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on chronic renal failure: •

Basic Guidelines for Chronic Renal Failure Alport syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000504.htm Chronic renal failure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000471.htm Diabetes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001214.htm Diabetes mellitus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001214.htm End-stage renal disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000500.htm Uremia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000508.htm

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Signs & Symptoms for Chronic Renal Failure Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Blood in the vomit Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003118.htm Blood pressure, high Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Breath odor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003058.htm Bruising Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Decreased alertness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Decreased sensation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Decreased urine output Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm General ill feeling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Hiccups Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003068.htm Hyperpigmentation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003242.htm

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Impotence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003164.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Menstrual irregularities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003263.htm Muscle twitching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003296.htm Nail abnormalities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003247.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Need to urinate at night Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm No urine output Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Paleness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003244.htm Pruritus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Skin, abnormally dark or light Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003242.htm Somnolence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Thirst, excessive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003085.htm

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Urination, excessive at night Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •

Diagnostics and Tests for Chronic Renal Failure Abdominal CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003789.htm Abdominal MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003796.htm Abdominal ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003777.htm Abdominal X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003815.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Arterial blood gas Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003855.htm Blood chemistry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm Creatinine clearance Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003611.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Dialysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003421.htm

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Erythropoietin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003683.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Potassium test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003484.htm PTH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003690.htm Renal scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003790.htm Serum magnesium - test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003487.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm Urinary casts Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003586.htm Urine volume Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003425.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Nutrition for Chronic Renal Failure Carbohydrate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002469.htm Carbohydrates Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002469.htm Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm Protein in diet Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm

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Surgery and Procedures for Chronic Renal Failure Kidney transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003005.htm

•

Background Topics for Chronic Renal Failure Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Electrolyte Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm Electrolytes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm Fractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Immune response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Kidney disease - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002172.htm Metabolism Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002257.htm Renal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002289.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm

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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

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CHRONIC RENAL FAILURE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Abscess: A localized, circumscribed collection of pus. [NIH] Acacia: Any leguminous woody vine or tree of the genus Acacia, also called locust or wattle. The gums and tanning agents obtained from Acacia are called gum arabic. [NIH] 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] 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] 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] 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] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] 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

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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] Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [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] Adenoma: A benign epithelial tumor with a glandular organization. [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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of

Dictionary 227

solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [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] 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 preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [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]

Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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] 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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH]

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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] Allogeneic: Taken from different individuals of the same species. [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] 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] 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 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] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group

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(-NH2). [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 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] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [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] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] 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] 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] 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] 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] 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]

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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] 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] 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] Ankle: That part of the lower limb directly above the foot. [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] 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 Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [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]

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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] 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] Antidepressant: A drug used to treat depression. [NIH] 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-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] 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]

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Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [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] Aqueous: Having to do with water. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [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]

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Aseptic: Free from infection or septic material; sterile. [EU] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [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] Asymptomatic: Having no signs or symptoms of disease. [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] 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] Attenuated: Strain with weakened or reduced virulence. [NIH] Audiometry: The testing of the acuity of the sense of hearing to determine the thresholds of the lowest intensity levels at which an individual can hear a set of tones. The frequencies between 125 and 8000 Hz are used to test air conduction thresholds, and the frequencies between 250 and 4000 Hz are used to test bone conduction thresholds. [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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Axilla: The underarm or armpit. [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] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH]

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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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [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 Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and

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displays. [NIH] 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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] 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 protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function. [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 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] 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

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percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [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 Transplantation: The transference of bone marrow from one human or animal to another. [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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [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 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] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] 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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budgets: Detailed financial plans for carrying out specific activities for a certain period of time. They include proposed income and expenditures. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bullous: Pertaining to or characterized by bullae. [EU] Bumetanide: A sulfamyl diuretic. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of

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body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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] 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] 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 Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] 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

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acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] 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] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [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 arrest: A sudden stop of heart function. [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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [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] 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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH]

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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] 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] Cefoperazone: Semisynthetic broad-spectrum cephalosporin with a tetrazolyl moiety that is resistant to beta-lactamase. It has been proposed especially against Pseudomonas infections. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [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 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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [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

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gravitational field generated in a centrifuge. [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 Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [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] 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] 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] 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] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [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]

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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] 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 Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [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] 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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [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] 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] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the

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action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [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] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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] 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 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.

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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] Complement 3: The fourth component to attach in the complement reaction sequence. It is a beta-globulin with a sedimentation coefficient of 5.5, a molecular weight of 185,000 and a serum concentration of 1.3 micrograms/ml. Its fragments have anaphylatoxic, chemotactic, and histaminic action and affect smooth muscle. [NIH] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complement Factor D: A serum protein which during the alternate pathway of complement activation converts the inactive factor B to complement 3 convertase. EC 3.4.21.46. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary 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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] 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] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [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)

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scan. [NIH] Computerized axial 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 CAT scan, computed tomography (CT scan), or computerized tomography. [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] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] 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] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] 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 medium: A substance that is introduced into or around a structure and, because of

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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. [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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [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] 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 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] 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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] 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]

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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] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [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 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] 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

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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] 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] Deamination: The removal of an amino group (NH2) from a chemical compound. [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] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [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] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Deuterium Oxide: The isotopic compound of hydrogen of mass 2 (deuterium) with oxygen. (From Grant & Hackh's Chemical Dictionary, 5th ed) It is used to study mechanisms and rates of chemical or nuclear reactions, as well as biological processes. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [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] Dialysis Solutions: Solutions prepared for exchange across a semipermeable membrane of solutes below a molecular size determined by the cutoff threshold of the membrane material. [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] Dietetics: The study and regulation of the diet. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond

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normal dimensions. [NIH] Dilate: Relax; expand. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [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] 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] Dimethyl: A volatile metabolite of the amino acid methionine. [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 determinant of therapy and prognosis. [NIH] 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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] 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] Diuretic: A drug that increases the production of urine. [NIH] 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] 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]

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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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] Duodenum: The first part of the small intestine. [NIH] Dysgenesis: Defective development. [EU] 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] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] 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] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ectopic: Pertaining to or characterized by ectopia. [EU]

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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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Enalaprilat: The active metabolite of enalapril and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion. [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]

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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] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [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-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] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [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]

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Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] 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] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [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] 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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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]

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Esophagus: The muscular tube through which food passes from the throat to the stomach. [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] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [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 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] 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]

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Extracorporeal: Situated or occurring outside the body. [EU] Extrarenal: Outside of the kidney. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Family Characteristics: Size and composition of the family. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [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] 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] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [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] 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] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [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] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the

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excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [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 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] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [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] 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] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [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] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] 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] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies

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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] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [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 Acid: Hydrochloric acid present in gastric juice. [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]

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] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes 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 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,

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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 Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] 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] Gestational: Psychosis attributable to or occurring during pregnancy. [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] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] 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

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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] 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] Glutamate: Excitatory neurotransmitter of the brain. [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]

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] 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]

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Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] Grafting: The operation of transfer of tissue from one site to another. [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] 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 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] 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] Gum Arabic: Powdered exudate from various Acacia species, especially A. senegal (Leguminosae). It forms mucilage or syrup in water. Gum arabic is used as a suspending agent, excipient, and emulsifier in foods and pharmaceuticals. [NIH] 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] 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] 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]

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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] 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] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by 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] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hematuria: Presence of blood in the urine. [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] Hemodialysis Solutions: Solutions prepared for hemodialysis. The composition of the predialysis solution may be varied in order to determine the effect of solvated metabolites on anoxia, malnutrition, acid-base balance, etc. Of principal interest are the effect of the choice of buffers (e.g., acetate or carbonate), the addition of cations (Na+, K+, Ca2+), and addition of carbohydrates (glucose). [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]

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Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [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]

Hepatic: Refers to the liver. [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] 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] 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]

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]

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Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [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] 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 Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [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] 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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrofluoric Acid: A solution of hydrogen fluoride in water. It is a colorless fuming liquid which can cause painful burns. [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]

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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] 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] Hyperammonemia: Metabolic disorder characterized by elevated level of ammonia in blood. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [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] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [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] 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] 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]

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Hypoglycemia: Abnormally low blood sugar [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypoventilation: A reduction in the amount of air entering the pulmonary alveoli. [NIH] Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [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] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [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]

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Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] 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] Indapamide: A sulfamyl diuretic with about 16x the effect of furosemide. It has also been shown to be an effective antihypertensive agent in the clinic. [NIH] 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] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU]

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Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] 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] 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] 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 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-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU]

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Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [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] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]

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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH]

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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] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [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 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] 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] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] 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] 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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no

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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] 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] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [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] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [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(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 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] Lithiasis: A condition characterized by the formation of calculi and concretions in the hollow organs or ducts of the body. They occur most often in the gallbladder, kidney, and

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lower urinary tract. [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] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] 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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [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] 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

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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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] 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] Malaise: A vague feeling of bodily discomfort. [EU] 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]

Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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

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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] 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] Membrane: A very thin layer of tissue that covers a surface. [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] 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] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [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] 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] 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 acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [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]

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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] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] 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] 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] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [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] 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] 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] 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

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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] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] 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] 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 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] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [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] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is

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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] 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] 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] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] 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

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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 Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [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] Neurologic: Having to do with nerves or the nervous system. [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, 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [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] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitter: Any of a group of substances that are released on excitation from the

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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] 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] 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] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood 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] 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] Nucleoli: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [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

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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] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [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 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] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [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] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [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]

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Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orf: A specific disease of sheep and goats caused by a pox-virus that is transmissible to man and characterized by vesiculation and ulceration of the lips. [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 Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] 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] 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] 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] 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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [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]

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

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potent and addicting than codeine. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pallor: A clinical manifestation consisting of an unnatural paleness of the skin. [NIH] 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] Pancreatic: Having to do with the pancreas. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Paradoxical: Occurring at variance with the normal rule. [EU] 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] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to

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therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] 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 Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [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]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [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] Pepsin: An enzyme made in the stomach that breaks down proteins. [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 T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)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] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perindopril: An angiotensin-converting enzyme inhibitor. It is used in patients with

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hypertension and heart failure. [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] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [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 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] 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 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] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or

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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] 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] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physicochemical: Pertaining to physics and chemistry. [EU] 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] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [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

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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] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] 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] Polycythemia Vera: A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs. [NIH] 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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Porokeratosis: A rare, chronic, progressive autosomal dominant disorder seen most often in males and usually appearing in early childhood. It is characterized by the formation of slightly atrophic patches surrounded by an elevated, keratotic border. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal System: A system of vessels in which blood, after passing through one capillary bed,

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is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portosystemic Shunt: An operation to create an opening between the portal vein and other veins around the liver. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: 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] Potentiates: 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] 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] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] 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

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in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Progeny: The offspring produced in any generation. [NIH] 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] 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] 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 Hazards Models: Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time. [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

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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). 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] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [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 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 C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to

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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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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] 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] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU]

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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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. [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 hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] 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]

Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyoderma Gangrenosum: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. [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] 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] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and

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control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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 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] 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] 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] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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

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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] 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] 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 Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Renal Replacement Therapy: Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. [NIH] 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] 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

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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 distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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]

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 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] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [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] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [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,

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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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of 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] 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] Sagittal: The line of direction passing through the body from back to front, or any vertical plane parallel to the medial plane of the body and inclusive of that plane; often restricted to the medial plane, the plane of the sagittal suture. [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] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Sclerotic: Pertaining to the outer coat of the eye; the sclera; hard, indurated or sclerosed. [NIH]

Screening: Checking for disease when there are no symptoms. [NIH]

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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] 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] 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] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [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] 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] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] 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] 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] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [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] 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]

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Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [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 receptormediated 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] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [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] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol 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] 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] Soybean Oil: Oil from soybean or soybean plant. [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] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [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

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the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [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 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] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] 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] 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] 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 the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

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] 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]

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Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] 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] 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] 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] Sulbactam: A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone. [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] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function

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(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] 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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] 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] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire 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] 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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH]

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Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] 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] 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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with 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] 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] 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]

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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [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

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concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [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] 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] 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] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case

Dictionary 303

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] 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] Translocation: The movement of material in solution inside the body of the plant. [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] 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 conferring calcium sensitivity to the cross-linked actin and myosin filaments. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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 suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH]

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Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [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] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] 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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] 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] 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] Ureters: Tubes that carry urine from the kidneys 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] 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] Urinate: To release urine from the bladder to the outside. [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] Urolithiasis: Stones in the urinary system. [NIH] Uterine Contraction: Contraction of the uterine muscle. [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] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] 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] 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 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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]

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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] 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 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] 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] Waiting Lists: Prospective patient listings for appointments. [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]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [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] 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] 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] 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,

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usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

309

INDEX A Abdomen, 225, 235, 236, 253, 268, 271, 279, 282, 283, 298 Abdominal, 35, 145, 174, 220, 225, 226, 248, 268, 273, 281, 283, 292, 304 Abdominal Pain, 225, 304 Aberrant, 54, 225 Abscess, 225, 295 Acacia, 143, 225, 260 Acceptor, 225, 270, 280 Acetaminophen, 15, 30, 225 Acetylcholine, 225, 278 Acidosis, 3, 27, 179, 225 Acquired Immunodeficiency Syndrome, 49, 225 Actin, 47, 225, 276, 303 Actinin, 88, 225, 250 Activities of Daily Living, 30, 225 Acuity, 127, 225, 233 Acute myelogenous leukemia, 225, 226 Acute myeloid leukemia, 140, 225, 226 Acute nonlymphocytic leukemia, 225, 226 Acute renal, 71, 151, 152, 153, 160, 163, 168, 170, 226, 262 Acute tubular, 157, 226 Adaptation, 29, 226 Adenine, 106, 226 Adenoma, 86, 226 Adenosine, 39, 226, 233, 284 Adipocytes, 226, 270 Adjustment, 11, 29, 147, 208, 226 Adjuvant, 99, 226 Adolescence, 226, 282 Adrenal Cortex, 226, 227, 245, 287, 292 Adrenal Glands, 226, 229, 292 Adrenal Medulla, 226, 252, 253 Adrenergic, 226, 231, 253 Adrenergic beta-Antagonists, 226, 231 Adsorption, 152, 161, 226 Adsorptive, 227 Adverse Effect, 77, 166, 187, 227, 296 Aerobic, 18, 227, 254, 274 Afferent, 227, 270 Affinity, 48, 227, 297 Agar, 227, 284 Age of Onset, 227, 304 Agenesis, 227, 259 Agonists, 160, 163, 226, 227

Airway, 227, 288, 296 Albumin, 17, 37, 82, 85, 110, 160, 227, 284 Albuminuria, 22, 171, 227 Aldosterone, 86, 107, 227 Alertness, 218, 227 Algorithms, 168, 228, 235 Alimentary, 228, 252, 281 Alkaline, 72, 91, 180, 225, 228, 229, 237, 301 Alkaline Phosphatase, 72, 91, 180, 228 Alkaloid, 228, 237, 242 Alkalosis, 21, 228, 301 Allogeneic, 94, 228, 260, 261 Allograft, 53, 56, 228 Allylamine, 228 Alopecia, 228, 246 Alpha Particles, 228, 290 Alternative medicine, 186, 228 Aluminum, 88, 179, 207, 228 Alveoli, 228, 247, 305 Ameliorating, 51, 153, 174, 228 Amenorrhea, 10, 125, 228 Amine, 127, 228, 262 Amino Acid Sequence, 228, 231, 254, 258 Amino-terminal, 73, 228 Amlodipine, 97, 229 Ammonia, 152, 161, 228, 229, 264, 304 Amniotic Fluid, 229, 285 Ampicillin, 85, 229 Amyloidosis, 92, 145, 229 Anabolic, 30, 74, 82, 111, 229, 248 Anabolic Steroids, 30, 229 Anaemia, 88, 124, 139, 150, 229, 273 Anaesthesia, 229, 266 Anal, 229, 253, 271, 275 Analgesic, 15, 30, 225, 229, 241, 280 Analog, 158, 229, 256, 279 Anaphylatoxins, 229, 243 Anastomosis, 42, 229 Anatomical, 132, 229, 233, 240, 244, 248, 251, 266, 294 Anemic, 16, 17, 51, 229 Aneurysm, 229, 257, 305 Angina, 154, 226, 229, 230, 268 Angina Pectoris, 226, 229, 230, 268 Anginal, 230, 278 Angiodysplasia, 174, 230 Angiography, 13, 230

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Angioplasty, 39, 67, 114, 188, 230, 276 Angiotensin converting enzyme inhibitor, 22, 108, 159, 230 Angiotensin I, 65, 88, 230 Angiotensin-Converting Enzyme Inhibitors, 156, 230, 231 Angiotensinogen, 31, 88, 230, 292 Animal model, 48, 51, 54, 56, 66, 69, 71, 230 Anions, 227, 230, 268, 295 Ankle, 79, 230 Anomalies, 18, 31, 230, 259 Anorexia, 74, 176, 188, 230, 232 Antagonism, 100, 230 Anterior Cerebral Artery, 230, 240 Anthropometric measurements, 180, 230 Anthropometry, 173, 231 Antibacterial, 231, 297, 299 Antibiotic, 229, 230, 231, 236, 282, 297, 299, 301 Antibodies, 17, 89, 231, 233, 260, 263, 265, 275, 284 Antibody, 7, 227, 231, 242, 243, 260, 263, 265, 266, 273, 275, 294, 297 Anticoagulant, 231, 288 Antidepressant, 176, 231 Antiemetic, 174, 231 Antifungal, 231, 269, 296 Antigen, 53, 227, 231, 243, 263, 265, 266, 267, 273 Antigen-Antibody Complex, 231, 243 Antihypertensive, 4, 20, 25, 52, 159, 231, 266 Antihypertensive Agents, 4, 159, 231 Anti-inflammatory, 30, 225, 231, 233, 248, 259, 266, 286 Anti-Inflammatory Agents, 231, 233 Antimetabolite, 231, 236, 256 Antineoplastic, 231, 236, 246, 256, 258, 296 Antioxidant, 55, 66, 88, 231, 280 Antiproliferative, 39, 232 Antipyretic, 225, 232 Antiviral, 232, 236, 267, 282 Anuria, 232, 269 Anxiety, 77, 226, 232 Aorta, 232, 245, 292, 299, 305 Apnea, 16, 155, 232 Apolipoproteins, 232, 270 Apoptosis, 28, 32, 54, 69, 72, 73, 76, 101, 232 Appetite Stimulants, 172, 232 Aqueous, 232, 234, 247, 263

Arachidonic Acid, 232, 287, 288 Arginine, 65, 98, 141, 159, 229, 232, 263, 278, 280 Arterial, 155, 156, 159, 167, 188, 220, 228, 232, 240, 264, 289, 300 Arteries, 232, 235, 245, 271, 275, 290, 301 Arteriolar, 232, 236, 292 Arterioles, 232, 235, 238, 274, 275 Arteriosclerosis, 232, 264 Arteriosus, 232, 290 Arteriovenous, 26, 39, 42, 89, 168, 188, 232, 274 Arteriovenous Fistula, 26, 42, 168, 188, 232 Arteritis, 154, 232 Artery, 29, 37, 40, 43, 56, 126, 127, 166, 229, 230, 232, 245, 248, 252, 276, 290, 292, 299 Aseptic, 233, 280, 298 Asphyxia, 154, 233 Aspirin, 15, 30, 233 Assay, 60, 72, 233 Asymptomatic, 124, 233, 234 ATP, 106, 233, 249, 258, 284, 288, 289 Atrial, 102, 233 Atrium, 233, 305 Atrophy, 30, 32, 47, 60, 95, 233, 277 Attenuated, 15, 233, 249 Audiometry, 106, 233 Autacoids, 233, 266 Autoantibodies, 136, 140, 233 Autoantigens, 233 Autologous, 142, 233, 261 Autologous bone marrow transplantation, 233, 261 Autonomic Neuropathy, 174, 233 Axilla, 233, 236 Axillary, 81, 233, 299 Axillary Vein, 233, 299 Axons, 28, 233, 277, 279 B Bacteria, 227, 231, 234, 244, 247, 252, 255, 257, 260, 263, 273, 274, 284, 295, 297, 298, 302, 303, 305 Bacterial Physiology, 226, 234 Bacterium, 234, 244, 262 Base, 20, 170, 226, 228, 234, 258, 261, 262, 269, 295, 300 Basement Membrane, 47, 61, 62, 234, 254, 269 Benign, 90, 103, 154, 226, 234, 257, 258, 276 Benign prostatic hyperplasia, 154, 234 Beta-Lactamases, 234, 299 Beta-Thalassemia, 123, 234

311

Bilateral, 10, 90, 234, 293 Bile, 152, 234, 256, 271, 298 Bile Acids, 152, 234, 298 Bile Acids and Salts, 234 Bile duct, 234 Biliary, 120, 234, 237 Bilirubin, 227, 234 Binding agent, 12, 234 Biochemical, 5, 12, 37, 62, 83, 91, 176, 177, 180, 181, 207, 231, 234, 256, 258, 269, 288 Bioengineering, 34, 198, 234 Biological response modifier, 235, 267 Biological therapy, 235, 260 Biomarkers, 70, 235 Biopsy, 17, 22, 66, 78, 235, 282 Biosynthesis, 232, 235, 246, 271, 288, 296 Biotechnology, 84, 86, 138, 186, 199, 235 Bladder, 233, 234, 235, 243, 264, 288, 304 Bleeding Time, 109, 235 Bloating, 235, 257 Blood Cell Count, 235, 261 Blood Coagulation, 235, 237, 301 Blood Glucose, 235, 261, 267 Blood pressure, 3, 6, 10, 13, 15, 18, 19, 20, 21, 22, 23, 24, 25, 27, 35, 37, 52, 59, 65, 79, 90, 91, 99, 100, 118, 159, 168, 171, 181, 188, 218, 220, 226, 231, 235, 238, 257, 264, 265, 275, 278, 283, 285, 290, 297 Blood transfusion, 18, 235 Blood urea, 180, 235, 269 Blood Volume, 235, 285 Blot, 48, 235 Body Composition, 91, 93, 96, 102, 121, 128, 235 Body Fluids, 157, 228, 235, 236, 237, 250, 256, 279, 292, 297, 303 Body Mass Index, 35, 236 Bone Development, 72, 236 Bone Marrow, 49, 175, 225, 226, 233, 236, 246, 253, 258, 261, 265, 272, 275, 285, 299 Bone Marrow Transplantation, 49, 236 Bowel, 152, 154, 229, 236, 268, 279, 283, 304 Brachial, 79, 106, 233, 236 Brachial Plexus, 106, 236 Bradykinin, 54, 236, 268, 278, 284 Brain Stem, 236, 240 Broad-spectrum, 229, 236, 239 Bromodeoxyuridine, 72, 236 Bronchitis, 236, 241 Buccal, 236, 271, 298 Budgets, 152, 161, 236

Buffers, 236, 261 Bullous, 113, 236 Bumetanide, 45, 236 Bypass, 154, 236, 276 C Cachexia, 37, 60, 237 Calcifediol, 237 Calcification, 14, 40, 116, 124, 127, 232, 237 Calcineurin, 116, 237 Calcitriol, 5, 12, 36, 72, 92, 106, 237 Calcium Carbonate, 142, 237 Calcium Channel Blockers, 231, 237 Calculi, 237, 259, 270 Calmodulin, 237 Caloric intake, 13, 237 Camptothecin, 237, 268 Capillary, 47, 156, 159, 235, 236, 238, 259, 285, 290, 305 Capillary Permeability, 236, 238 Capsules, 238, 259 Carbohydrate, 84, 142, 162, 221, 238, 285, 295 Carbon Dioxide, 16, 155, 161, 238, 257, 293, 305 Carcinogenic, 238, 267, 279, 287, 298 Carcinoma, 238 Cardiac, 6, 13, 18, 20, 27, 35, 43, 45, 107, 116, 122, 154, 165, 167, 169, 226, 228, 238, 253, 254, 257, 261, 264, 268, 275, 276, 298, 299 Cardiac arrest, 154, 238 Cardiac Output, 238, 299 Cardiogenic, 154, 238 Cardiomyopathy, 166, 238 Cardiovascular System, 6, 233, 238 Carnitine, 16, 176, 238 Case report, 85, 86, 111, 116, 120, 125, 238, 241 Catabolism, 7, 9, 176, 238 Catheter, 18, 112, 238, 252 Catheterization, 230, 239, 276 Cations, 239, 261, 268 Causal, 239, 253 Cause of Death, 6, 13, 27, 165, 239 Cefoperazone, 85, 239 Cell Adhesion, 140, 163, 239, 267 Cell Adhesion Molecules, 140, 163, 239 Cell Cycle, 64, 239 Cell Death, 232, 239, 276 Cell Differentiation, 239, 296 Cell Division, 157, 234, 239, 260, 268, 274, 284

312

Chronic Renal Failure

Cell membrane, 45, 237, 239, 248, 251, 284 Cell motility, 239, 262 Cell proliferation, 39, 42, 85, 232, 239, 296 Cell Size, 239, 256 Cell Survival, 239, 260 Cell Transplantation, 94, 239, 261 Central Nervous System, 225, 237, 239, 251, 257, 259, 263, 279, 283 Centrifugation, 239, 261, 300 Cerebellum, 154, 240 Cerebral, 154, 230, 236, 240, 245, 253, 256, 262, 263 Cerebral Infarction, 154, 240, 263 Cerebrospinal, 240, 263, 296 Cerebrospinal fluid, 240, 263, 296 Cerebrovascular, 237, 238, 240 Cerebrum, 240 Cervical, 236, 240 Chemotactic Factors, 240, 243 Chemotherapeutic agent, 240, 249 Chemotherapy, 29, 49, 140, 177, 240 Chickenpox, 7, 240 Chin, 137, 143, 240, 273 Cholesterol, 13, 35, 40, 137, 181, 234, 240, 241, 245, 250, 264, 270, 271, 296, 298 Cholesterol Esters, 240, 270 Chondrocytes, 72, 240, 255 Chorioretinitis, 240, 293 Choroid, 240, 245, 293 Chromaffin System, 240, 252 Chromatin, 232, 241, 272 Chromosomal, 58, 241, 258, 263, 284, 285 Chromosome, 21, 48, 50, 58, 69, 241, 244, 270 Chronic Disease, 44, 45, 237, 241 Chronic Obstructive Pulmonary Disease, 154, 241 Chylomicrons, 241, 270 Circulatory system, 241, 252 Cirrhosis, 17, 122, 154, 241, 285 CIS, 83, 241, 293 Clamp, 45, 241 Clathrin, 241, 252 Clinical study, 137, 241, 245 Cloning, 47, 58, 64, 68, 69, 235, 241 Coated Vesicles, 241, 252 Codeine, 241, 280 Codon, 61, 241, 258 Coenzyme, 241, 271, 296 Cofactor, 241, 288, 301 Cognition, 18, 242 Cohort Studies, 242, 253

Colchicine, 113, 242 Colitis, 174, 242 Collagen, 61, 72, 85, 234, 242, 254, 255, 272, 285, 287 Collapse, 242, 296 Colloidal, 227, 242, 251, 295 Colon, 242, 269, 304 Colonic Polyps, 174, 242 Colorectal, 144, 242 Colorectal Cancer, 144, 242 Combinatorial, 28, 242 Comorbidity, 40, 53, 75, 242 Complement, 49, 229, 242, 243, 258, 267, 284 Complement 3, 243 Complement Activation, 229, 243 Complement Factor D, 49, 243 Complementary and alternative medicine, 135, 146, 243 Complementary medicine, 135, 243 Complete remission, 66, 243, 292 Complete response, 243 Compliance, 22, 33, 37, 40, 55, 63, 77, 177, 179, 243 Compress, 243, 262 Computational Biology, 199, 243 Computed tomography, 40, 121, 243, 244 Computerized axial tomography, 243, 244 Computerized tomography, 243, 244 Concentric, 6, 101, 244 Concomitant, 30, 244 Conduction, 85, 233, 244 Confusion, 218, 244, 304 Congestive heart failure, 6, 7, 14, 124, 132, 154, 166, 244 Conjugated, 53, 234, 244, 246 Conjugation, 60, 244 Connective Tissue, 236, 242, 244, 255, 271, 273, 294, 300 Consciousness, 229, 244, 247, 249, 289, 298 Consolidation, 140, 244 Constipation, 8, 244 Constitutional, 174, 244, 293 Constriction, 244, 268, 289, 305 Constriction, Pathologic, 244, 305 Contractility, 165, 230, 244 Contraindications, ii, 207, 244 Contrast medium, 230, 244, 245 Control group, 11, 75, 80, 245, 287, 291 Controlled clinical trial, 42, 245, 291 Controlled study, 22, 97, 141, 245 Conus, 245, 290

313

Convulsions, 245, 250, 286 Coordination, 63, 240, 245 Cornea, 245, 294, 306 Coronary, 35, 40, 43, 56, 98, 104, 114, 119, 123, 126, 166, 230, 238, 245, 264, 275 Coronary Angiography, 98, 123, 245 Coronary Arteriosclerosis, 245, 275 Coronary Artery Bypass, 43, 245 Coronary heart disease, 35, 238, 245 Coronary Thrombosis, 245, 275 Cortex, 245 Cortical, 37, 245, 295 Corticosteroids, 245, 259, 286 Cortisol, 227, 245 Cortisone, 245, 248, 286 Cranial, 240, 245, 268, 279, 283 Creatine, 31, 246 Creatinine clearance, 30, 160, 167, 220, 246 Critical Care, 177, 246 Cross-Sectional Studies, 246, 253 Curative, 246, 294, 301 Cutaneous, 246, 271 Cyclic, 237, 246, 260, 278, 288 Cyclophosphamide, 66, 246 Cyclosporine, 160, 246 Cyst, 47, 100, 246 Cystathionine beta-Synthase, 246, 264 Cytochrome, 147, 246 Cytokine, 28, 37, 51, 57, 78, 80, 246, 267, 296 Cytomegalovirus, 75, 246 Cytoplasm, 232, 239, 247, 260, 272, 293, 300 Cytoskeleton, 47, 247, 267 Cytotoxic, 247, 265, 267, 296 D Data Collection, 40, 75, 77, 182, 247 De novo, 35, 71, 83, 247 Deamination, 247, 304 Defense Mechanisms, 247, 267 Degenerative, 230, 245, 247, 262 Dehydroepiandrosterone, 156, 247 Deletion, 32, 48, 88, 101, 232, 247, 257 Delivery of Health Care, 247, 260 Dementia, 44, 225, 247 Denaturation, 247, 262 Dendrites, 28, 247, 277 Dendritic, 28, 247 Dental Care, 179, 247 Dental Caries, 25, 247 Dental Plaque, 23, 25, 247 Dentition, 26, 247

Depolarization, 117, 248, 296 Dermatosis, 87, 113, 248 Desensitization, 248, 265 Deuterium, 102, 248, 263 Deuterium Oxide, 102, 248 Dexamethasone, 45, 248 Diagnostic procedure, 149, 186, 248 Dialysate, 53, 55, 56, 63, 80, 168, 172, 248 Dialysis Solutions, 21, 55, 160, 161, 248 Dialyzer, 56, 63, 248, 261 Diaphragm, 47, 248 Diarrhea, 76, 248 Diastole, 248 Diastolic, 15, 166, 248, 264 Diastolic blood pressure, 15, 248 Dietetics, 63, 181, 248 Dietitian, 19, 168, 248 Diffusion, 238, 248, 249, 260, 266, 292, 304 Digestion, 228, 234, 236, 248, 250, 257, 268, 271, 282, 298, 305 Digestive tract, 233, 248, 296 Dihydrotestosterone, 248, 291 Dilatation, Pathologic, 248, 305 Dilate, 119, 249 Dilated cardiomyopathy, 154, 249 Dilation, 236, 249, 263, 305 Dilution, 102, 249 Dimethyl, 249, 268 Dipyridamole, 39, 41, 249 Direct, iii, 19, 34, 46, 51, 52, 54, 55, 68, 77, 157, 191, 249, 283, 291, 299 Discrete, 249, 271, 288, 306 Disease Progression, 7, 20, 32, 59, 79, 249 Disparity, 40, 53, 249 Disposition, 124, 249 Dissection, 85, 249 Dissociation, 55, 227, 249 Dissociative Disorders, 249 Distal, 31, 39, 48, 81, 245, 249, 289 Diuretic, 236, 249, 256, 266 Diuretics, Thiazide, 231, 249 DNA Topoisomerase, 249, 258 Double-blind, 42, 55, 57, 98, 135, 141, 250 Double-blinded, 55, 57, 250 Drug Interactions, 192, 250 Drug Tolerance, 250, 302 Duct, 239, 250, 254, 272, 294, 298 Duodenum, 234, 250, 257, 282, 298 Dysgenesis, 54, 250 Dysgerminoma, 104, 250 Dyslipidemia, 6, 27, 125, 250 Dyspepsia, 97, 99, 250

314

Chronic Renal Failure

Dysplasia, 11, 250 Dystrophic, 250, 253 Dystrophin, 250, 275 E Echocardiography, 13, 116, 250 Eclampsia, 250, 286 Ectopic, 49, 250 Edema, 251, 256, 262, 268, 276, 277, 286 Effector, 225, 242, 251 Efferent, 159, 251 Efficacy, 7, 12, 18, 40, 42, 43, 51, 53, 55, 56, 59, 66, 75, 81, 82, 86, 99, 101, 251 Elastin, 242, 251, 254 Electrolyte, 20, 46, 114, 170, 179, 222, 227, 251, 256, 261, 269, 279, 286, 297 Electrons, 231, 234, 251, 268, 280, 290 Electrophoresis, 70, 251, 262 Electroporation, 51, 251 Emaciation, 225, 251 Embolectomy, 251, 301 Embryo, 236, 239, 251, 258, 266, 280, 286 Emphysema, 241, 251 Empiric, 71, 251 Enalapril, 23, 91, 99, 251 Enalaprilat, 107, 251 Enamel, 25, 247, 251 Encephalopathy, 76, 159, 251 Endarterectomy, 230, 252 Endemic, 252, 298 Endocrine Glands, 252, 281 Endocrine System, 167, 252 Endocytosis, 60, 252 Endogenous, 5, 57, 64, 83, 170, 233, 252, 279, 288, 302 Endosomes, 45, 252 Endothelial cell, 65, 140, 154, 252, 255, 301 Endothelium, 100, 169, 230, 252, 278 Endothelium-derived, 252, 278 Endotoxic, 154, 252 Endotoxin, 90, 252 Energy balance, 252, 270 Energy Intake, 13, 22, 46, 252 Enhancer, 252, 293 Enkephalins, 155, 252, 278, 279 Enteral Nutrition, 167, 252 Environmental Health, 198, 200, 252 Enzymatic, 96, 237, 243, 247, 252, 262, 293 Enzyme Inhibitors, 159, 253, 284 Epidemic, 9, 25, 27, 35, 58, 253, 298 Epidemiologic Studies, 15, 253 Epidemiological, 165, 253 Epidermal, 157, 253

Epidermal Growth Factor, 157, 253 Epidermis, 253 Epidermolysis Bullosa, 103, 253 Epidural, 116, 253 Epigastric, 253, 281 Epinephrine, 226, 253, 278, 304 Epiphyseal, 72, 253 Epithelial, 32, 47, 54, 67, 69, 71, 76, 101, 226, 253, 262, 269 Epithelial Cells, 32, 47, 67, 69, 253, 262, 269 Epithelium, 76, 234, 252, 253, 257, 306 Erectile, 10, 154, 253 Erection, 253 Erythrocytes, 98, 229, 235, 236, 253, 262, 291 Erythropoiesis, 55, 117, 253 Esophagus, 248, 254, 282, 291, 298 Ether, 154, 254 Ethnic Groups, 38, 254 Eukaryotic Cells, 254, 266, 278, 280, 304 Evacuation, 244, 254, 257 Excitability, 45, 117, 254 Excitation, 254, 256, 277 Excrete, 232, 254, 269, 292 Exercise Test, 254 Exercise Tolerance, 176, 254 Exhaustion, 230, 254 Exocrine, 254, 281 Exogenous, 12, 51, 57, 170, 227, 252, 254, 257, 288, 304 Exon, 48, 254 Extracellular, 23, 33, 34, 39, 45, 51, 62, 163, 244, 252, 254, 255, 267, 272, 297, 301 Extracellular Matrix, 33, 51, 163, 244, 254, 255, 267, 272 Extracellular Matrix Proteins, 33, 254, 272 Extracellular Space, 254 Extracorporeal, 151, 161, 255, 261 Extrarenal, 45, 255 Extravasation, 255, 261 Extremity, 236, 255 F Family Characteristics, 166, 255 Family Planning, 199, 255 Fat, 138, 180, 181, 226, 232, 234, 236, 245, 255, 270, 285, 297, 303 Fatigue, 10, 94, 101, 174, 218, 255, 261 Fatty acids, 140, 227, 255, 287 Feces, 244, 255 Femur, 90, 255 Ferritin, 55, 255

315

Fetus, 236, 253, 255, 286, 305 Fibrinogen, 28, 75, 101, 107, 110, 255, 284, 301 Fibroblast Growth Factor, 157, 255 Fibroblasts, 67, 255, 267 Fibronectin, 87, 255 Fibrosis, 13, 47, 51, 52, 60, 67, 69, 136, 228, 255, 294 Filtration, 4, 48, 60, 69, 139, 255, 269 Fistula, 18, 39, 42, 89, 255, 279 Flatus, 255, 257 Flow Cytometry, 122, 255 Fluid Therapy, 256, 279 Fluorescence, 255, 256 Fluorescent Dyes, 255, 256 Fluorouracil, 249, 256 Folate, 82, 256 Fold, 256, 279 Folic Acid, 107, 121, 136, 137, 143, 256 Foramen, 240, 256, 283 Forearm, 92, 112, 235, 256 Fossa, 240, 256 Fractionation, 256, 300 Frail Elderly, 30, 256 Free Radicals, 28, 231, 249, 256, 276 Frontal Lobe, 230, 240, 256 Furosemide, 103, 256, 266 G Gait, 30, 256 Gallbladder, 225, 234, 256, 270 Ganglion, 256, 279, 306 Ganglionic Blockers, 231, 257 Gangrene, 56, 111, 257 Gas, 220, 229, 238, 248, 255, 257, 263, 278, 290, 299, 305 Gas exchange, 257, 290, 305 Gastric, 82, 119, 154, 176, 238, 253, 257, 262, 282 Gastric Acid, 119, 257 Gastric Emptying, 176, 257 Gastric Juices, 257, 282 Gastric Mucosa, 154, 257 Gastrin, 257, 263 Gastrointestinal, 55, 76, 152, 174, 177, 230, 236, 252, 253, 257, 298, 299, 303 Gastrointestinal tract, 152, 230, 257, 298, 303 Gastroparesis, 97, 174, 176, 257 Gastrostomy, 252, 257 Gene Deletion, 48, 257 Gene Expression, 38, 48, 51, 54, 67, 68, 71, 80, 257

Gene Targeting, 64, 257 Gene Therapy, 49, 51, 61, 150, 257 Genetic Code, 258, 278 Genetic Engineering, 24, 235, 241, 258 Genetic Markers, 58, 258 Genetic Techniques, 71, 258 Genetics, 58, 68, 244, 258, 274 Genistein, 57, 258 Genital, 233, 258 Genomics, 68, 258 Genotype, 47, 78, 258, 283 Geriatric, 8, 57, 166, 258 Germ cell tumors, 250, 258 Germ Cells, 250, 258, 280, 301 Germ Layers, 236, 258 Gestational, 48, 54, 258 Gingival Hyperplasia, 26, 258 Gingivitis, 23, 247, 258 Ginseng, 146, 258 Gland, 12, 34, 226, 240, 245, 258, 271, 281, 284, 288, 295, 298, 299, 301 Glomerular Filtration Rate, 4, 8, 10, 19, 24, 36, 37, 52, 59, 66, 171, 173, 258, 269 Glomeruli, 47, 69, 70, 259 Glomerulonephritis, 57, 69, 95, 157, 259, 271 Glomerulosclerosis, 10, 38, 66, 69, 78, 88, 157, 259 Glomerulus, 69, 258, 259, 276 Glucocorticoid, 156, 248, 259, 286 Glucose, 38, 65, 85, 110, 176, 180, 188, 235, 248, 259, 261, 267, 294 Glucose Intolerance, 85, 248, 259 Glutamate, 28, 259, 283 Glutamic Acid, 256, 259, 262, 278, 287 Glutathione Peroxidase, 142, 259 Glycoprotein, 253, 255, 259, 260, 269, 301 Glycosaminoglycans, 254, 259 Goats, 259, 280 Gonad, 250, 259 Gonadal, 104, 129, 259, 298 Gonadal Dysgenesis, 104, 129, 259 Gout, 50, 242, 259 Governing Board, 260, 286 Gp120, 260, 282 Grade, 104, 120, 250, 260 Graft, 41, 56, 160, 188, 260, 276 Graft Rejection, 160, 260 Grafting, 43, 245, 260, 266 Gram-negative, 252, 260 Granulocytes, 260, 296, 306 Grasses, 256, 260

316

Chronic Renal Failure

Growth factors, 10, 66, 84, 104, 157, 172, 178, 260 Growth Plate, 72, 260 Guanylate Cyclase, 260, 278 Gum Arabic, 225, 260 H Haemodialysis, 89, 100, 128, 144, 260 Haptens, 227, 260 Health Care Costs, 74, 260 Health Expenditures, 260 Health Services, 78, 247, 261 Health Status, 33, 80, 261 Heart attack, 238, 261 Heart failure, 35, 39, 154, 173, 230, 251, 261, 283 Hematocrit, 7, 8, 18, 19, 32, 51, 166, 235, 261 Hematoma, 116, 261, 262 Hematopoietic Stem Cell Transplantation, 142, 261 Hematuria, 35, 261 Hemodiafiltration, 53, 151, 261, 304 Hemodialysis Solutions, 55, 56, 261 Hemodialyzer, 151, 182, 261 Hemodynamics, 47, 261 Hemofiltration, 261, 304 Hemoglobin, 6, 8, 15, 19, 26, 37, 56, 166, 229, 234, 235, 253, 261, 262, 270, 301 Hemoglobin C, 229, 262 Hemoglobinopathies, 258, 262 Hemolytic, 76, 262, 301 Hemorrhage, 154, 230, 262, 276, 298 Hemorrhagic stroke, 154, 262 Hemostasis, 262, 267 Hepatic, 106, 124, 159, 227, 262, 271, 286, 296 Hepatitis, 17, 99, 100, 109, 112, 120, 179, 262 Hepatocyte, 51, 262 Hepatocyte Growth Factor, 51, 262 Hereditary, 61, 259, 262, 277, 301 Heredity, 257, 258, 262 Heterodimers, 262, 267, 303 Heteroduplex Analysis, 48, 262 Heterogeneity, 38, 227, 262 Histamine, 229, 262 Histidine, 158, 262 Histology, 37, 72, 162, 262 Histone Deacetylase, 54, 263 Histones, 237, 241, 263 Homeostasis, 14, 45, 82, 156, 162, 170, 175, 263

Homodimer, 263, 303 Homologous, 257, 258, 263, 300 Hormonal, 175, 233, 263, 306 Hormone Replacement Therapy, 9, 263 Hormone therapy, 37, 91, 96, 105, 263 Human growth hormone, 9, 12, 72, 99, 187, 263 Humoral, 260, 263 Hybridomas, 251, 263, 267 Hydrocephalus, 263, 268 Hydrofluoric Acid, 263, 296 Hydrogen, 225, 228, 234, 236, 238, 247, 248, 254, 259, 263, 264, 270, 275, 278, 280, 289 Hydrogen Peroxide, 259, 263, 270 Hydrolysis, 234, 264, 283, 285, 289 Hydronephrosis, 31, 264 Hydrophobic, 264, 270 Hydroxylation, 33, 237, 264 Hydroxylysine, 242, 264 Hydroxyproline, 242, 264 Hyperammonemia, 159, 264 Hypercalcemia, 125, 264 Hypercholesterolemia, 156, 250, 264 Hyperglycemia, 62, 264 Hyperhomocysteinemia, 82, 107, 112, 137, 246, 264 Hyperkalaemia, 117, 264 Hyperlipidemia, 166, 167, 250, 264 Hyperlipoproteinemia, 264 Hyperplasia, 34, 39, 42, 62, 66, 264 Hypertension, Pulmonary, 154, 264 Hypertension, Renal, 107, 264 Hypertension, Renovascular, 264 Hypertriglyceridemia, 108, 156, 250, 264 Hypertrophy, 6, 7, 13, 62, 101, 167, 234, 264 Hyperuricemia, 50, 156, 259, 264 Hypoglycemia, 108, 126, 154, 265 Hypoplasia, 31, 265 Hypotension, 21, 80, 245, 257, 265 Hypoventilation, 155, 265 Hypovolemia, 21, 265 Hypoxia, 32, 51, 67, 229, 265 I Idiopathic, 69, 174, 265, 290 Imidazole, 159, 262, 265 Immune response, 56, 109, 222, 226, 231, 233, 245, 260, 265, 299, 305, 306 Immune system, 235, 265, 272, 305, 306 Immunity, 225, 265, 267 Immunization, 109, 265, 287

317

Immunochemistry, 61, 265 Immunodeficiency, 85, 225, 265 Immunogenic, 7, 265 Immunohistochemistry, 64, 265 Immunologic, 78, 177, 240, 265 Immunology, 226, 227, 256, 265 Immunophilin, 237, 265 Immunosuppressant, 256, 265, 296 Immunosuppression, 56, 83, 111, 116, 265, 272, 279 Immunosuppressive, 56, 168, 237, 246, 259, 265, 300 Immunosuppressive Agents, 265 Impairment, 44, 110, 266, 273 Implantation, 83, 266 Impotence, 10, 219, 253, 266 In situ, 48, 72, 266 In Situ Hybridization, 48, 72, 266 In vitro, 29, 31, 32, 34, 52, 65, 66, 67, 71, 258, 266, 300 In vivo, 32, 34, 51, 52, 65, 66, 67, 71, 72, 84, 258, 266, 272, 300, 301 Incision, 266, 268 Indapamide, 102, 266 Indomethacin, 21, 266 Induction, 32, 54, 56, 62, 83, 140, 257, 266, 267, 296 Infancy, 187, 266, 293 Infarction, 240, 262, 266, 292 Infection Control, 17, 266 Infiltration, 60, 259, 266, 306 Infusion, 55, 266, 276, 303 Inhalation, 100, 266, 285 Initiation, 4, 8, 10, 17, 24, 25, 41, 67, 77, 176, 177, 267, 287, 302 Innervation, 236, 267 Insight, 71, 76, 166, 267 Insulin, 9, 10, 24, 28, 45, 52, 56, 70, 83, 93, 97, 105, 111, 128, 157, 267, 281, 304 Insulin-dependent diabetes mellitus, 267 Insulin-like, 9, 28, 52, 93, 105, 128, 157, 267 Integrins, 163, 267 Interferon, 111, 267 Interferon-alpha, 267 Interleukin-1, 111, 267 Interleukin-18, 111, 267 Interleukin-2, 267 Interleukin-6, 75, 125, 267 Intermittent, 24, 72, 106, 256, 267, 271, 283 Internal Medicine, 7, 33, 37, 39, 46, 54, 56, 71, 72, 73, 87, 113, 114, 119, 123, 181, 268, 276

Interpersonal Relations, 77, 268 Interphase, 268, 278 Interstitial, 47, 50, 60, 67, 69, 136, 157, 254, 268, 276 Intestinal, 76, 111, 117, 152, 154, 178, 237, 268, 306 Intestine, 76, 234, 236, 242, 268, 269 Intoxication, 268, 306 Intracellular, 31, 76, 82, 153, 237, 241, 258, 266, 267, 268, 278, 286, 288, 296 Intracranial Hypertension, 90, 263, 268 Intramuscular, 51, 109, 268, 281 Intraperitoneal, 173, 268 Intravascular, 49, 52, 268 Intravenous, 15, 16, 55, 66, 111, 124, 266, 268, 281 Intrinsic, 115, 159, 227, 234, 268 Inulin, 259, 268 Invasive, 67, 265, 268 Ions, 234, 236, 237, 249, 251, 263, 268 Irinotecan, 144, 268 Ischemia, 71, 111, 152, 153, 154, 157, 233, 262, 268, 276, 292 Isoflavones, 57, 268 Isradipine, 135, 268 J Jejunostomy, 252, 268 K Kallidin, 236, 268 Kb, 198, 269 Keratolytic, 247, 269 Keto, 83, 138, 143, 156, 157, 158, 269 Ketoconazole, 155, 156, 269 Kidney Failure, Acute, 269 Kidney Failure, Chronic, 269 Kidney stone, 264, 269, 292, 304 Kidney Transplantation, 17, 24, 53, 56, 74, 162, 171, 174, 187, 204, 269 Kilobase, 48, 269 Kinetic, 37, 112, 180, 269 L Labile, 157, 242, 269 Lactation, 269, 281 Lag, 55, 269 Laminin, 234, 254, 269 Large Intestine, 242, 248, 268, 269, 291, 296 Latency, 81, 269 Latent, 269, 286 Least-Squares Analysis, 270, 292 Leptin, 96, 270 Lesion, 5, 12, 66, 69, 245, 270, 271, 304 Lethal, 76, 270

318

Chronic Renal Failure

Lethargy, 10, 219, 263, 270 Leucine, 22, 270 Leukemia, 142, 258, 270 Leukocytosis, 270, 285 Life Expectancy, 41, 63, 270 Ligament, 270, 288 Ligands, 239, 267, 270 Ligation, 32, 270 Likelihood Functions, 270, 292 Linear Models, 270, 292 Linkage, 21, 35, 38, 48, 50, 58, 73, 258, 270 Lipid, 8, 13, 15, 76, 86, 98, 113, 136, 140, 143, 232, 238, 267, 269, 270, 280, 303 Lipid Peroxidation, 98, 270, 280 Lipoprotein, 36, 94, 105, 107, 141, 250, 260, 270, 271 Lipoprotein(a), 36, 105, 107, 270 Lithiasis, 120, 270 Liver Cirrhosis, 103, 271 Lobe, 230, 240, 263, 271, 281 Localization, 48, 64, 265, 271 Localized, 225, 229, 247, 250, 261, 266, 269, 271, 284, 304 Locomotion, 271, 284 Locomotor, 28, 271 Logistic Models, 271, 292 Longitudinal study, 29, 43, 44, 77, 271 Long-Term Care, 44, 271 Lovastatin, 271, 296 Low-density lipoprotein, 94, 140, 250, 270, 271 Lupus, 101, 271, 300 Lupus Nephritis, 101, 271 Lymph, 233, 240, 241, 250, 252, 271, 272, 299 Lymph node, 233, 240, 250, 271, 272 Lymphatic, 252, 266, 271, 272, 273, 285, 298 Lymphocyte Count, 225, 272 Lymphocyte Depletion, 265, 272 Lymphocytes, 225, 231, 237, 263, 265, 267, 272, 298, 300, 306 Lymphoid, 231, 245, 272 Lymphoma, 125, 272 Lysine, 158, 262, 263, 264, 272 M Macrophage, 56, 267, 272 Malaise, 174, 272 Malformation, 61, 113, 272 Malignancy, 24, 250, 272 Malignant, 117, 154, 225, 231, 250, 258, 272, 275, 276, 294

Malignant tumor, 272, 275 Malnutrition, 7, 9, 26, 64, 74, 77, 104, 172, 173, 176, 177, 181, 187, 188, 227, 233, 237, 261, 272 Malondialdehyde, 107, 272 Mammary, 245, 272 Mammogram, 237, 272, 274 Manifest, 81, 176, 272 Matrix metalloproteinase, 67, 272 Medial, 232, 272, 294 Mediate, 31, 62, 92, 155, 239, 272 Mediator, 57, 267, 272 Medical Records, 77, 273, 293 Medical Staff, 250, 273 MEDLINE, 199, 273 Megaloblastic, 256, 273 Melanin, 273, 283, 304 Memory, 230, 247, 273 Menstruation, 228, 273 Mental, iv, 27, 44, 45, 77, 198, 200, 240, 242, 244, 247, 249, 255, 273, 287, 289, 290, 292, 294, 304 Mental Disorders, 273, 287, 289 Mental Health, iv, 27, 44, 77, 198, 200, 273, 287, 290 Mental Processes, 249, 273, 289 Mentors, 36, 44, 79, 273 Mercury, 256, 273 Mesenchymal, 69, 253, 273 Mesentery, 273, 283 Meta-Analysis, 82, 105, 273 Metabolic acidosis, 9, 22, 27, 98, 104, 160, 167, 273 Metabolic disorder, 36, 49, 259, 264, 273 Metabolite, 237, 249, 251, 271, 273 Metastasis, 239, 272, 274 Metastatic, 14, 144, 274 Methylprednisolone, 66, 274 Microbe, 274, 302 Microbiology, 226, 274 Microcalcifications, 237, 274 Microcirculation, 65, 98, 271, 274 Microorganism, 241, 274, 282, 306 Micro-organism, 247, 274 Microscopy, 47, 234, 262, 274, 278 Migration, 163, 274 Mitochondria, 274, 276, 280 Mitochondrial Swelling, 274, 276 Mitosis, 69, 232, 274 Modeling, 44, 180, 274 Modification, 21, 36, 59, 177, 258, 274, 290 Molecular Probes, 251, 274

319

Monitor, 36, 79, 96, 173, 246, 275, 278 Monoclonal, 71, 263, 275, 294 Monoclonal antibodies, 71, 275, 294 Monocyte, 90, 140, 275 Monotherapy, 135, 275 Morphogenesis, 31, 275 Morphology, 96, 275 Motility, 266, 275 Motion Sickness, 275, 276 Mucins, 247, 275, 294 Mucosa, 179, 257, 271, 275, 298 Mucus, 275, 304 Multiple Myeloma, 142, 275 Multivariate Analysis, 103, 275 Muscle Proteins, 60, 275 Myelofibrosis, 275, 285 Myocardial infarction, 14, 154, 173, 245, 275 Myocardial Ischemia, 154, 230, 275 Myocardial Reperfusion, 275, 276, 293 Myocardial Reperfusion Injury, 276, 293 Myocardium, 230, 275, 276 Myopathy, 176, 276 Myosin, 237, 276, 303 N Narcotic, 276, 280 Nasogastric, 101, 252, 276 Natriuresis, 230, 276 Nausea, 174, 188, 219, 231, 257, 276, 289, 304 NCI, 1, 197, 241, 276 Necrosis, 157, 232, 240, 266, 275, 276, 292 Neoplasia, 110, 276 Neoplasm, 250, 276, 294 Nephritis, 61, 157, 162, 276 Nephrologist, 3, 19, 20, 77, 173, 276 Nephron, 31, 52, 90, 92, 94, 96, 103, 106, 110, 114, 119, 127, 137, 138, 142, 156, 259, 276 Nephrosis, 277 Nephrotic, 103, 113, 175, 277 Nephrotic Syndrome, 103, 113, 175, 277 Nephrotoxic, 162, 180, 277 Nerve Endings, 277, 300 Nerve Fibers, 236, 277 Nervous System, 227, 239, 272, 277, 283, 300 Networks, 62, 126, 277 Neural, 126, 227, 257, 263, 277 Neurodegenerative Diseases, 28, 277 Neurologic, 177, 263, 277 Neuronal, 28, 277

Neurons, 28, 47, 247, 257, 277, 300 Neuropathy, 62, 233, 277 Neuropeptide, 37, 277 Neurophysiology, 248, 277 Neuropsychology, 44, 277 Neuroretinitis, 277, 293 Neurosecretory Systems, 252, 277 Neurotoxic, 28, 277 Neurotransmitter, 225, 226, 236, 259, 262, 277, 296, 299 Neutrons, 228, 278, 290 Neutrophil, 108, 278 Nifedipine, 99, 278 Nitric Oxide, 28, 64, 110, 278 Nitrogen, 5, 22, 143, 156, 159, 167, 177, 180, 228, 246, 254, 269, 278, 303 Nonmalignant, 94, 278 Normotensive, 21, 78, 278 Nuclear, 57, 58, 100, 116, 238, 244, 248, 251, 254, 257, 276, 278, 304 Nuclei, 228, 230, 244, 251, 258, 263, 274, 278, 279, 289 Nucleic acid, 150, 258, 266, 278 Nucleoli, 76, 278 Nucleus, 230, 232, 241, 246, 247, 248, 254, 272, 278, 289 Nursing Care, 278, 282 Nutrition Assessment, 167, 180, 278 Nutritional Status, 8, 9, 24, 25, 37, 59, 74, 75, 96, 98, 172, 173, 176, 178, 188, 278 Nutritional Support, 11, 257, 279 O Occult, 9, 279 Occupational Exposure, 35, 279 Octreotide, 126, 279 Ocular, 61, 279 Odds Ratio, 279, 292 Office Visits, 4, 279 Oliguria, 269, 279 Omentum, 83, 279 Oncogene, 262, 279 Oncogenic, 267, 279 Ophthalmologic, 40, 279 Ophthalmology, 127, 279 Opioid Peptides, 252, 279 Opportunistic Infections, 225, 279 Optic Nerve, 277, 279, 289, 293, 294 Oral Health, 25, 280 Oral Hygiene, 23, 280 Orf, 73, 280 Organ Culture, 64, 280 Organ Transplantation, 166, 280

320

Chronic Renal Failure

Organelles, 33, 239, 241, 247, 280, 284 Ornithine, 158, 159, 280 Orthostatic, 279, 280 Osmotic, 227, 274, 280, 295 Osseointegration, 236, 280 Osteodystrophy, 5, 19, 22, 26, 122, 179, 280 Osteogenesis, 236, 280 Osteoporosis, 14, 128, 280 Outpatient, 3, 8, 46, 280 Ovary, 259, 280 Overexpress, 54, 280 Oxidation, 22, 94, 225, 231, 246, 259, 270, 280 Oxidative Stress, 55, 56, 57, 66, 100, 107, 169, 280 Oxycodone, 132, 280 Oxygenation, 155, 262, 281 Oxytocin, 155, 281 P P53 gene, 54, 281 Palate, 281, 298 Palliative, 44, 281, 301 Pallor, 179, 281 Pancreas, 53, 56, 168, 225, 235, 267, 281, 303 Pancreas Transplant, 168, 281 Pancreas Transplantation, 168, 281 Pancreatic, 174, 238, 281 Papilla, 281 Papillary, 31, 281 Paradoxical, 66, 281 Parathyroid Glands, 207, 281, 294 Parathyroid hormone, 4, 5, 8, 9, 12, 14, 34, 37, 72, 92, 98, 120, 175, 237, 281 Parathyroidectomy, 12, 15, 87, 175, 281 Parenteral, 55, 82, 100, 167, 252, 281 Parenteral Nutrition, 82, 167, 281 Parietal, 230, 281, 283 Partial remission, 281, 292 Particle, 282, 303 Pathogen, 17, 76, 282 Pathologic, 225, 232, 235, 245, 282, 293 Pathologic Processes, 232, 282 Pathophysiology, 13, 50, 52, 67, 68, 76, 108, 119, 159, 167, 170, 171, 175, 179, 282 Patient Care Management, 174, 178, 282 Patient Education, 206, 207, 212, 214, 223, 282 Patient Selection, 53, 175, 181, 282 Pediatrics, 20, 26, 32, 46, 54, 66, 67, 68, 71, 94, 100, 105, 109, 122, 123, 282 Pelvic, 282, 288

Pelvis, 225, 269, 282, 305 Penicillin, 229, 230, 282 Pepsin, 282 Peptic, 174, 282 Peptic Ulcer, 174, 282 Peptide, 70, 72, 102, 154, 255, 270, 279, 282, 285, 288, 289 Peptide T, 154, 282 Perception, 8, 282, 294 Percutaneous, 43, 104, 114, 119, 282 Perfusion, 52, 126, 265, 282 Pericarditis, 97, 282 Pericardium, 282, 300 Perindopril, 102, 282 Periodontal disease, 26, 283 Periodontitis, 258, 283 Peripheral blood, 57, 117, 261, 267, 283 Peripheral Nervous System, 252, 277, 278, 283, 299 Peripheral Vascular Disease, 6, 35, 283 Peripheral vision, 283, 306 Peritoneal Cavity, 176, 268, 283 Peritoneum, 181, 273, 279, 283 Peroxide, 140, 283 Pharmacologic, 60, 230, 233, 283, 302 Phenobarbital, 95, 283 Phenotype, 32, 47, 48, 54, 78, 257, 283 Phenylalanine, 283, 304 Phospholipases, 283, 296 Phospholipids, 255, 270, 284 Phosphorus, 8, 14, 27, 37, 40, 155, 156, 175, 180, 181, 188, 207, 237, 281, 284 Phosphorylation, 32, 284, 289 Physical Examination, 13, 37, 173, 284 Physicochemical, 265, 284 Physiologic, 7, 42, 81, 175, 176, 180, 235, 268, 273, 284, 287, 291, 293 Physiology, 45, 52, 61, 64, 68, 74, 81, 99, 181, 276, 277, 284 Pilot study, 36, 59, 67, 106, 140, 284 Pituitary Gland, 255, 284 Plants, 228, 238, 258, 259, 268, 275, 284, 285, 294, 302 Plaque, 23, 25, 230, 284 Plasma cells, 231, 275, 284 Plasma protein, 227, 284, 295 Plasmid, 49, 51, 284, 305 Plastids, 280, 284 Platelet Activation, 284, 296 Platelet Aggregation, 229, 278, 285, 288, 301 Platelet-Derived Growth Factor, 157, 285

321

Platelets, 278, 284, 285 Plexus, 236, 285 Pneumonia, 103, 244, 285 Poisoning, 145, 268, 273, 276, 285 Polycystic, 47, 64, 69, 285 Polycythemia Vera, 109, 285 Polyhydramnios, 21, 285 Polypeptide, 228, 242, 253, 255, 285, 301, 307 Polyposis, 242, 285 Polysaccharide, 231, 285, 289 Polytetrafluoroethylene, 41, 188, 285 Polyunsaturated fat, 138, 285, 301 Population Control, 11, 285 Porokeratosis, 96, 285 Portal Hypertension, 93, 285 Portal System, 159, 285 Portal Vein, 285, 286 Portosystemic Shunt, 93, 286 Posterior, 229, 232, 240, 281, 286, 294 Postmenopausal, 280, 286 Postnatal, 286, 298 Postoperative, 154, 168, 286 Postsynaptic, 286, 296 Post-synaptic, 286, 300 Potassium, 21, 45, 141, 179, 180, 181, 188, 221, 227, 249, 264, 286 Potentiates, 157, 267, 286 Potentiation, 286, 296 Practice Guidelines, 18, 116, 118, 139, 166, 200, 286 Precursor, 230, 232, 246, 251, 252, 283, 286, 303, 304, 306 Predisposition, 57, 68, 70, 286 Prednisolone, 274, 286 Prednisone, 66, 187, 286 Preeclampsia, 154, 286 Prenatal, 21, 154, 251, 286 Prenatal Diagnosis, 21, 286 Primary endpoint, 64, 287 Primary Prevention, 39, 287 Progeny, 54, 244, 287 Progesterone, 287, 298 Prokinetic Drugs, 174, 287 Proline, 242, 264, 287 Promoter, 38, 48, 54, 69, 79, 83, 287 Promotor, 287, 293 Prone, 38, 73, 287 Prophylaxis, 287, 293, 305 Proportional Hazards Models, 53, 287 Prospective Studies, 63, 76, 287

Prospective study, 28, 32, 35, 36, 44, 75, 114, 271, 287 Prostaglandin, 160, 163, 230, 287, 288, 301 Prostaglandin Endoperoxides, 288, 301 Prostaglandins A, 160, 163, 266, 287, 288 Prostaglandins D, 288 Prostaglandins H, 160, 164, 288 Prostate, 154, 234, 235, 288, 303 Prostatic Hyperplasia, 288 Protease, 70, 288 Protease Inhibitors, 70, 288 Protein Binding, 54, 288 Protein C, 53, 75, 167, 179, 227, 228, 232, 241, 255, 270, 275, 288, 289, 303, 304 Protein Folding, 61, 288 Protein Kinases, 62, 288 Protein S, 85, 138, 156, 235, 258, 263, 288, 293, 301 Protein-Energy Malnutrition, 172, 289 Protein-Tyrosine Kinase, 258, 289 Proteinuria, 22, 35, 37, 47, 59, 94, 109, 141, 159, 162, 171, 259, 275, 277, 286, 289 Proteoglycans, 234, 254, 289 Proteolytic, 61, 243, 255, 289 Proteome, 70, 289 Protocol, 23, 46, 49, 56, 63, 289 Protons, 228, 263, 289, 290 Protozoa, 244, 274, 289 Proximal, 33, 60, 81, 249, 289, 295 Pseudotumor Cerebri, 268, 289 Psychiatry, 117, 289, 299, 305 Psychic, 273, 289, 295 Psychoactive, 289, 306 Psychological Theory, 29, 289 Psychology, 29, 249, 277, 289 Psychophysiology, 277, 289 Puberty, 12, 22, 26, 289 Public Health, 36, 183, 200, 290 Public Policy, 199, 290 Publishing, 84, 290 Pulmonary, 120, 154, 235, 254, 261, 264, 265, 269, 290, 305 Pulmonary Alveoli, 265, 290 Pulmonary Artery, 120, 235, 290, 305 Pulmonary Circulation, 264, 290 Pulmonary Edema, 269, 290 Pulmonary hypertension, 120, 154, 290 Pulse, 275, 290 Purulent, 290 Putrefaction, 257, 290 Pyoderma, 127, 290 Pyoderma Gangrenosum, 127, 290

322

Chronic Renal Failure

Q Quality of Life, 7, 10, 18, 20, 27, 29, 32, 44, 46, 56, 74, 80, 83, 87, 172, 175, 176, 290 Quaternary, 288, 290 R Race, 11, 14, 35, 78, 274, 290 Radiation, 48, 230, 256, 265, 290, 306 Radioactive, 263, 266, 274, 275, 278, 279, 290, 300, 304 Radiological, 282, 290 Random Allocation, 290, 291 Randomization, 66, 81, 291 Randomized, 22, 25, 37, 39, 40, 42, 46, 55, 57, 59, 63, 80, 81, 97, 98, 99, 105, 135, 141, 251, 291 Randomized clinical trial, 25, 59, 291 Randomized Controlled Trials, 105, 291 Reactivation, 84, 291 Receptor, 23, 28, 34, 52, 54, 71, 72, 76, 80, 90, 95, 100, 154, 159, 160, 163, 226, 231, 260, 262, 282, 283, 291, 296 Recombination, 244, 257, 258, 291 Rectum, 242, 248, 255, 257, 269, 288, 291 Recurrence, 187, 291 Red blood cells, 8, 18, 175, 253, 262, 291, 294 Reductase, 39, 40, 271, 291, 296 Refer, 1, 34, 236, 242, 271, 278, 291, 302 Reflux, 103, 109, 120, 123, 291 Refraction, 291, 297 Refractory, 103, 291 Regeneration, 83, 255, 291 Regimen, 7, 29, 66, 167, 173, 251, 291 Regression Analysis, 7, 11, 291 Rehabilitative, 172, 176, 292 Relative risk, 6, 15, 59, 292 Remission, 66, 291, 292 Renal Artery, 85, 264, 292 Renal cell carcinoma, 90, 292 Renal Dialysis, 13, 29, 41, 292 Renal Osteodystrophy, 5, 12, 15, 20, 37, 57, 92, 167, 172, 175, 179, 292 Renal Replacement Therapy, 11, 13, 17, 21, 33, 78, 121, 163, 170, 171, 172, 173, 292 Renal tubular, 32, 47, 69, 157, 292 Renin, 23, 31, 107, 230, 292 Renin-Angiotensin System, 31, 230, 292 Renovascular, 80, 160, 292 Reperfusion, 62, 276, 292 Reperfusion Injury, 62, 292 Resorption, 237, 263, 293

Respiration, 232, 238, 274, 275, 293 Respiratory distress syndrome, 154, 293 Respiratory Physiology, 293, 305 Response Elements, 83, 293 Retina, 47, 240, 245, 277, 279, 293, 294, 306 Retinal, 249, 279, 293 Retinitis, 47, 293 Retinoids, 293, 306 Retrospective, 8, 11, 19, 21, 30, 43, 53, 63, 86, 293 Retrospective study, 86, 293 Retroviral vector, 257, 293 Ribose, 226, 293 Ribosome, 293, 303 Rickets, 237, 293, 306 Risk patient, 126, 294 Rituximab, 125, 294 Rod, 234, 241, 294 S Sagittal, 35, 294 Saliva, 294 Salivary, 25, 179, 246, 247, 294, 299 Salivary glands, 246, 247, 294 Saphenous, 245, 294 Saphenous Vein, 245, 294 Saponins, 294, 298 Sarcoma, 174, 294 Schizoid, 294, 306 Schizophrenia, 294, 306 Schizotypal Personality Disorder, 294, 306 Sclera, 240, 245, 294 Sclerosis, 38, 52, 159, 232, 294 Sclerotic, 67, 294 Screening, 15, 17, 22, 38, 40, 52, 58, 241, 294 Secretion, 9, 119, 253, 262, 267, 269, 275, 279, 295, 303, 305 Segmental, 66, 69, 78, 88, 259, 295 Segmentation, 295 Seizures, 219, 295, 298 Selection Bias, 53, 295 Self Care, 225, 295 Semen, 288, 295 Seminoma, 250, 295 Senile, 280, 295 Sepsis, 154, 273, 295 Septal, 65, 230, 295 Septic, 60, 154, 233, 295 Sequence Analysis, 69, 295 Sequence Homology, 282, 295 Serum Albumin, 32, 63, 64, 75, 82, 295 Sessile, 242, 295

323

Sex Characteristics, 226, 289, 295, 301 Shock, 154, 265, 295, 303 Shunt, 18, 296 Side effect, 10, 24, 30, 179, 191, 193, 208, 227, 235, 246, 264, 296, 302 Sigmoidal, 34, 296 Signal Transduction, 62, 237, 296 Signs and Symptoms, 292, 296 Silicon, 33, 296 Silicon Dioxide, 33, 296 Simvastatin, 40, 296 Sirolimus, 56, 66, 116, 296 Skeletal, 12, 49, 68, 84, 85, 123, 241, 275, 296, 303 Skeleton, 225, 255, 287, 296 Skull, 296, 300 Sleep apnea, 16, 155, 186, 296 Small intestine, 241, 250, 263, 268, 276, 296 Smooth muscle, 39, 42, 70, 154, 228, 229, 233, 237, 243, 262, 268, 288, 292, 297, 299 Social Environment, 290, 297 Social Isolation, 9, 294, 297 Social Security, 9, 291, 297 Social Support, 44, 77, 297 Social Work, 63, 207, 297 Socioeconomic Factors, 73, 297 Sodium, 11, 22, 45, 155, 179, 180, 181, 188, 227, 249, 251, 259, 276, 297 Soft tissue, 14, 236, 296, 297 Solvent, 87, 280, 297 Soybean Oil, 285, 297 Specialist, 19, 22, 74, 209, 249, 297 Species, 228, 239, 242, 253, 260, 274, 275, 280, 290, 295, 297, 298, 303, 305, 306 Specificity, 58, 227, 297 Spectrometer, 65, 297 Spectrum, 6, 65, 269, 297, 299 Sperm, 241, 258, 297 Spinal cord, 236, 239, 240, 253, 257, 277, 283, 297, 299, 300 Spleen, 229, 246, 272, 285, 298 Splenomegaly, 285, 298 Sporadic, 54, 88, 277, 298 Stabilization, 162, 298 Status Epilepticus, 154, 298 Steel, 241, 298 Stem Cells, 83, 253, 261, 298 Stenosis, 26, 39, 41, 67, 188, 298 Stent, 85, 298 Sterile, 151, 233, 281, 298 Sterility, 246, 298 Steroid, 30, 56, 66, 234, 245, 294, 296, 298

Stimulants, 258, 298 Stimulus, 244, 250, 254, 267, 269, 298, 301 Stomach, 225, 248, 254, 257, 263, 276, 279, 282, 283, 291, 296, 298 Stomatitis, 179, 298 Streptococcal, 25, 298 Streptococcus, 26, 298 Stress, 13, 18, 28, 29, 44, 54, 55, 56, 62, 66, 119, 126, 173, 178, 219, 245, 276, 280, 286, 298 Stricture, 298 Stroke, 28, 35, 45, 123, 154, 173, 198, 238, 262, 298, 299 Stroke Volume, 28, 238, 299 Stromal, 54, 299 Stupor, 270, 276, 299 Subacute, 266, 299 Subarachnoid, 154, 299 Subclavian, 188, 233, 299 Subclavian Artery, 299 Subclavian Vein, 188, 233, 299 Subclinical, 122, 127, 266, 295, 299 Subcutaneous, 124, 226, 251, 281, 299 Submaxillary, 253, 299 Substance P, 273, 295, 299 Substrate, 65, 253, 299 Suction, 255, 299 Sulbactam, 85, 299 Sulfur, 254, 299 Superoxide, 28, 299 Supplementation, 11, 27, 55, 65, 82, 136, 137, 141, 142, 144, 167, 172, 181, 207, 299 Support group, 222, 299 Suppression, 12, 57, 299 Survival Analysis, 287, 299 Survival Rate, 11, 26, 162, 300 Sympathetic Nervous System, 230, 300 Symphysis, 240, 288, 300 Symptomatic, 50, 300 Symptomatology, 7, 300 Synaptic, 278, 296, 300 Synaptosomes, 103, 300 Synergistic, 28, 39, 92, 300 Systemic lupus erythematosus, 122, 271, 300 Systolic, 15, 113, 165, 264, 300 T Tacrolimus, 56, 300 Technetium, 127, 300 Temporal, 34, 61, 300 Terminator, 241, 300 Testis, 250, 259, 301

324

Chronic Renal Failure

Testosterone, 229, 291, 301 Tetany, 281, 301 Tetracycline, 64, 301 Thalassemia, 234, 301 Therapeutics, 158, 166, 192, 301 Thermal, 158, 249, 278, 301 Thoracic, 236, 248, 272, 299, 301, 306 Threonine, 282, 301 Threshold, 31, 248, 254, 264, 301 Thrombectomy, 188, 251, 301 Thrombin, 255, 285, 288, 301 Thrombomodulin, 288, 301 Thromboses, 82, 301 Thrombosis, 26, 39, 41, 42, 67, 107, 188, 267, 289, 298, 301 Thromboxanes, 232, 288, 301 Thymidine, 236, 301 Thyroid, 45, 86, 281, 301, 302, 304 Thyroid Gland, 281, 301, 302 Thyroiditis, 87, 302 Thyroxine, 103, 227, 283, 302 Tolerance, 178, 259, 302 Tomography, 302 Tone, 68, 278, 280, 302 Tonus, 302 Tooth Preparation, 226, 302 Topoisomerase inhibitors, 268, 302 Toxaemia, 286, 302 Toxic, iv, 54, 244, 250, 260, 261, 265, 277, 302 Toxicity, 55, 157, 160, 179, 250, 273, 302 Toxicology, 142, 200, 302 Toxin, 9, 76, 252, 302 Trace element, 296, 302 Trachea, 301, 302 Traction, 241, 302 Transcription Factors, 67, 293, 302 Transcutaneous, 16, 302 Transduction, 62, 296, 302 Transfection, 235, 251, 258, 303 Transforming Growth Factor beta, 78, 303 Transfusion, 303 Translation, 76, 303 Translational, 68, 79, 303 Translocation, 76, 303 Transmitter, 225, 272, 303 Trauma, 154, 263, 276, 303 Triglyceride, 15, 264, 303 Tropomyosin, 275, 303 Troponin, 122, 275, 303 Tryptophan, 242, 303 Tuberculosis, 145, 271, 303

Tumor marker, 235, 303 Tumor suppressor gene, 281, 303 Tunica, 252, 275, 304 Type 2 diabetes, 22, 24, 49, 58, 73, 114, 304 Tyrosine, 57, 146, 289, 304 U Ubiquitin, 60, 304 Ulcer, 304 Ulceration, 154, 174, 280, 282, 304 Ulcerative colitis, 154, 290, 304 Ultrafiltration, 151, 173, 261, 304 Ultrasonography, 102, 125, 304 Uranium, 300, 304 Urea, 5, 13, 21, 22, 25, 37, 65, 126, 152, 160, 161, 167, 168, 177, 179, 180, 235, 280, 304 Ureters, 269, 292, 304, 305 Urethra, 234, 288, 304 Uric, 50, 259, 264, 304 Urinary, 31, 37, 54, 89, 126, 156, 159, 160, 178, 221, 237, 263, 271, 279, 304 Urinary tract, 31, 54, 271, 304 Urinate, 219, 304 Urolithiasis, 168, 304 Uterine Contraction, 281, 304 Uterus, 87, 240, 273, 287, 305 V Vaccination, 6, 7, 99, 109, 127, 305 Vaccine, 7, 115, 226, 289, 305 Vacuoles, 252, 280, 305 Valves, 33, 305 Varicella, 6, 7, 127, 305 Vasoactive, 62, 154, 305 Vasoconstriction, 155, 253, 305 Vasodilation, 100, 169, 230, 251, 305 Vasodilator, 231, 236, 262, 276, 278, 305 Vector, 49, 51, 150, 303, 305 Vein, 41, 112, 229, 232, 268, 278, 285, 286, 294, 299, 305 Venous, 26, 42, 67, 232, 233, 235, 240, 289, 305 Venous blood, 235, 240, 305 Ventilation, 100, 305 Ventricle, 290, 300, 305 Ventricular, 6, 7, 13, 37, 101, 113, 165, 263, 276, 305 Venules, 235, 238, 274, 305 Vesicoureteral, 123, 305 Veterinary Medicine, 199, 305 Viral, 279, 302, 305 Virulence, 233, 302, 305 Virus, 7, 17, 85, 100, 112, 179, 225, 240, 252, 258, 260, 267, 280, 284, 293, 303, 305, 306

325

Visceral, 69, 233, 283, 306 Visual field, 124, 289, 306 Vitamin A, 158, 159, 162, 306 Vitamin D, 33, 82, 128, 172, 175, 294, 306 Vitreous, 240, 293, 306 Vitreous Body, 240, 293, 306 Vitro, 34, 65, 306 Vivo, 34, 48, 52, 64, 66, 67, 272, 306 W Waiting Lists, 152, 161, 306 White blood cell, 231, 272, 275, 278, 284, 306 Windpipe, 301, 306

Withdrawal, 108, 306 Womb, 305, 306 Wound Healing, 239, 255, 267, 272, 306 X Xenograft, 230, 306 X-ray, 102, 220, 221, 243, 244, 245, 256, 272, 278, 306 Y Yeasts, 283, 306 Z Zoster, 7, 306 Zygote, 244, 306 Zymogen, 288, 306

326

Chronic Renal Failure

327

328

Chronic Renal Failure

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