LIVER 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., 1960Liver Failure: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84483-6 1. Liver 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.
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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 liver 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 LIVER FAILURE .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Liver Failure.................................................................................. 7 E-Journals: PubMed Central ....................................................................................................... 59 The National Library of Medicine: PubMed ................................................................................ 59 CHAPTER 2. NUTRITION AND LIVER FAILURE .............................................................................. 105 Overview.................................................................................................................................... 105 Finding Nutrition Studies on Liver Failure .............................................................................. 105 Federal Resources on Nutrition ................................................................................................. 107 Additional Web Resources ......................................................................................................... 107 CHAPTER 3. CLINICAL TRIALS AND LIVER FAILURE .................................................................... 109 Overview.................................................................................................................................... 109 Recent Trials on Liver Failure ................................................................................................... 109 Keeping Current on Clinical Trials ........................................................................................... 110 CHAPTER 4. PATENTS ON LIVER FAILURE .................................................................................... 113 Overview.................................................................................................................................... 113 Patents on Liver Failure............................................................................................................. 113 Patent Applications on Liver Failure......................................................................................... 116 Keeping Current ........................................................................................................................ 119 CHAPTER 5. BOOKS ON LIVER FAILURE ........................................................................................ 121 Overview.................................................................................................................................... 121 Book Summaries: Federal Agencies............................................................................................ 121 Book Summaries: Online Booksellers......................................................................................... 125 Chapters on Liver Failure .......................................................................................................... 126 CHAPTER 6. MULTIMEDIA ON LIVER FAILURE ............................................................................. 129 Overview.................................................................................................................................... 129 Video Recordings ....................................................................................................................... 129 CHAPTER 7. PERIODICALS AND NEWS ON LIVER FAILURE .......................................................... 133 Overview.................................................................................................................................... 133 News Services and Press Releases.............................................................................................. 133 Newsletter Articles .................................................................................................................... 135 Academic Periodicals covering Liver Failure............................................................................. 136 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 137 Overview.................................................................................................................................... 137 U.S. Pharmacopeia..................................................................................................................... 137 Commercial Databases ............................................................................................................... 138 Researching Orphan Drugs ....................................................................................................... 138 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 143 Overview.................................................................................................................................... 143 NIH Guidelines.......................................................................................................................... 143 NIH Databases........................................................................................................................... 145 Other Commercial Databases..................................................................................................... 147 The Genome Project and Liver Failure ...................................................................................... 147 APPENDIX B. PATIENT RESOURCES ............................................................................................... 151 Overview.................................................................................................................................... 151 Patient Guideline Sources.......................................................................................................... 151 Finding Associations.................................................................................................................. 177 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 179 Overview.................................................................................................................................... 179
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Preparation................................................................................................................................. 179 Finding a Local Medical Library................................................................................................ 179 Medical Libraries in the U.S. and Canada ................................................................................. 179 ONLINE GLOSSARIES................................................................................................................ 185 Online Dictionary Directories ................................................................................................... 185 LIVER FAILURE DICTIONARY ................................................................................................ 187 INDEX .............................................................................................................................................. 269
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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 liver 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 liver 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 liver 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 liver 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 liver 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 liver 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 LIVER FAILURE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on liver 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 liver 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 “liver 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: •
Review Article: The Management of Acute Liver Failure Source: Alimentary Pharmacology and Therapeutics. 12(5): 405-418. May 1998. Contact: Available from Blackwell Science Ltd. Journal Subscriptions, P.O. Box 88, Oxford, OX2 0NE, England. Phone 44 (0) 1865 206180 or 44 (0) 1865 206038. Fax 44 (0) 1865 206219. Summary: Acute liver failure (ALF) is a relatively uncommon but dramatic clinical syndrome with high mortality rates, in which a previously normal liver fails within days or weeks. This article reviews the management of ALF. A number of conditions can cause this sudden dysfunction, which triggers a multiorgan response. Paracetamol overdose remains the major cause of ALF in the United Kingdom, while viral hepatitis is the commonest cause worldwide. The severity of clinical signs and illness depends on
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Liver Failure
the adverse metabolic consequences of loss of liver function, the systemic effect of toxins from the necrotic liver, and the rate and degree of regeneration. In addition, and as a result of toxic injury, the immune system is compromised; secondary bacterial infections and endotoxinemia give rise to symptoms similar to those of septic shock. Cerebral edema is the leading cause of death in patients with ALF. Despite advances in intensive care and the development of new treatment modalities, mortality remains high and ALF is best managed in specialist centers. Orthotopic liver transplantation is the only new treatment modality that has made a significant impact in improving outcome. Bioartificial liver support systems and hepatocyte transplantation are promising new options that may change the future management of ALF. 5 tables. 120 references. (AAM). •
Acute Liver Failure Source: Journal of Clinical Gastroenterology. 33(3): 191-198. 2001. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: Acute liver failure is defined as hepatic encephalopathy (a brain manifestation of extensive liver damage) complicating acute liver injury. This article reviews the definitions, etiologies, prognostic factors, and issues in the management of patients with acute liver failure (ALF). The most common etiologies (causes) are acute viral hepatitis A and B, medication overdose (e.g., acetaminophen), idiosyncratic drugs reactions, ingestion of other toxins (e.g., amanita mushroom poisoning), and metabolic disorders (e.g., Reye's syndrome). Despite advances in intensive care management, mortality (death) continues to be high (40 to 80 percent) and is partly related to ALF's complications, such as cerebral edema (fluid accumulation), sepsis, hypoglycemia (low blood glucose), gastrointestinal bleeding, and acute renal (kidney) failure. Several prognostic models have been developed to determine which patients will spontaneously recover. Treatment is directed at early recognition of the complications and general supportive measures. The only proven therapy for those who are unlikely to recover is liver transplantation. Therefore, recognition of ALF is paramount, and urgent referral to a transplant center is critical to assess transplantation status. 2 figures. 5 tables. 62 references.
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Artificial and Bioartificial Support Systems for Acute and Acute-on-Chronic Liver Failure: A Systematic Review Source: JAMA. Journal of the American Medical Association. 289 (2): 217-222. January 8, 2003. Summary: Artificial and bioartificial support systems may provide a bridge for patients with severe liver disease to their recovery or the availability of transplantation. Liver support must include removal of toxins, synthesis of products, and treatment of inflammation. This article reports on a review undertaken to evaluate the effect of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. Of 528 references identified, 12 randomized trials with 483 patients were included. Eight nonrandomized studies were included in explorative analyses. Overall, support systems had no significant effect on mortality compared with standard medical therapy. Analyses indicated that the effect of support systems depended on the type of liver failure. Support systems appeared to reduce mortality by 33 percent in acute-on-chronic liver failure, but not in acute liver failure. 3 tables. 43 references.
Studies
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Nefazodone-Induced Liver Failure: Report of Three Cases Source: Annals of Internal Medicine. 130(4, Part 1): 285-288. February 16, 1999. 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: Liver failure is a rare but devastating result of drug toxicity. This article describes three cases of subfulminant liver failure that were probably caused by nefazodone, a new antidepressant that is a synthetically derived phenylpiperazine. The patients were three women, aged 16 to 57 years of age. Nefazodone was administered for 14 to 28 weeks before the onset of symptoms. The duration of jaundice before onset of encephalopathy ranged from 4 to 6 weeks. All cases of liver failure had similar histologic appearance, with prominent necrosis in the centrolobular areas (zone 3). One patient had a successful liver transplant, one underwent transplantation but died, and the third improved without transplantation. The temporal onset of disease after the start of nefazodone therapy suggested severe hepatocellular injury caused by the drug. The authors recommend that routine liver chemistries should be performed before starting nefazodone therapy and patients should be monitored regularly; therapy should be discontinued if liver enzyme concentrations become abnormal. 1 figure. 1 table. 11 references. (AA-M).
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Hepatitis B Infection in Patients with Acute Liver Failure in the United States Source: Hepatology. 33(4): 972-976. April 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Occult (hidden) hepatitis B virus (HBV) infection has been reported in 30 to 50 percent of patients with acute liver failure (ALF) in small case series. This article reports on a study undertaken to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera (blood products) from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR positive samples were sequenced. Sera and or liver from 139 patients (39 males, 100 females; mean age 42 years) were studied between January 1998 and December 1999. Twelve patients were diagnosed with hepatitis B, one with hepatitis B, C, and D coinfection, and 22 had indeterminate etiology (cause). HBV DNA was detected in the sera of 9 patients (6 percent); all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. 1 appendix. 3 tables. 34 references.
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Molecular Adsorbents Recirculating System (MARS) in Liver Failure Source: Alimentary Pharmacology and Therapeutics. 16(Suppl 5): 32-38. December 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email:
[email protected]. Website: www.blackwell-science.com.
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Summary: Recently, different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. This article discusses the molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialyzed across an albumin-impregnated membrane against a recirculated albumin-containing solution. The authors note that the MARS seems to be effective in removing albumin-bound toxins, such as fatty acids, bile acids, and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. The real usefulness of MARS in these settings is, at present, under evaluation in randomized controlled clinical trials. 2 figures. 1 table. 55 references. •
Dialysis in Liver Failure and Liver Transplantation Source: Transplantation Proceedings. 25(2): 1740. April 1993. Summary: This article briefly reports on a study designed to define the long-term survival of liver transplant candidates and recipients who also require dialysis and to determine the factors important in predicting outcome. From May 1988 to June 1989, 141 patients with liver failure or liver transplant recipients required hemodialysis at the University of Pittsburgh. Eighty-eight patients received liver transplants; of these, 3 were dialyzed before transplantation, 7 were receiving dialysis at the time of transplantation, and 78 were dialyzed after transplantation. Actuarial patient survival was 51 percent after 18 months in the transplanted group. The authors summarize that acute renal failure after liver transplantation typically occurs in the setting of multiorgan failure and is associated with high mortality rates. They note that the leading cause of renal failure was ischemic acute tubular necrosis and not hepatorenal syndrome or nephrotoxic immunosuppressants. 5 references.
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Halothane-Induced Acute Liver Failure: Continuing Occurrence and Use of Liver Transplantation Source: European Journal of Gastroenterology and Hepatology. 10(8): 635-639. August 1998. Contact: Available from Lippincott Williams and Wilkins, 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Summary: This article reports on a study undertaken to determine whether the frequency and pattern of acute liver failure (ALF) following halothane anesthesia had decreased during the past 11 years (compared with a previous series of 48 patients referred between 1965 and 1984) and whether clinical outcome had been altered by the introduction of liver transplantation. Clinical data were complete in 15 of the 18 patients studied. Ten of these patients had at least one previous halothane anesthesia, with documented clinical complications following the earlier exposure in 6 of the 10 patients. Four had been reexposed to halothane within 1 month of the penultimate halothane anesthesia. Of the 15 patients, four survived with medical management alone and 11 patients fulfilled transplant criteria. Four of the group were not listed because of their rapidly deteriorating medical state and died, and of the 7 patients who were listed, 3 died without a liver becoming available and 4 were transplanted, one of whom survived. No patient who had grade 4 encephalopathy and a prothrombin time greater than 50 seconds survived without a transplant. The authors briefly report a survey of other European liver centers that recorded a total of 19 patients with halothane-induced
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ALF; of these, 13 patients were transplanted with 9 survivors. The authors conclude that cases of halothane-induced acute liver failure still occur, albeit at a lower frequency than previously, and the Committee on Safety of Medicines guidelines are not being followed. The authors note that the results of transplantation in these patients are encouraging. 1 table. 20 references. (AA-M).
Federally Funded Research on Liver Failure The U.S. Government supports a variety of research studies relating to liver 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 liver 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 liver failure. The following is typical of the type of information found when searching the CRISP database for liver failure: •
Project Title: A MULTI-CENTER THERAPY TRIAL FOR ACUTE LIVER FAILURE Principal Investigator & Institution: Lee, William M.; Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Acute liver failure is a rare condition in which liver cell damage occurs rapidly leading to severe multi-organ failure requiring high resource utilization and, frequently, a fatal outcome. Prior to 1997, little research had been performed in the US regarding this condition because of the lack of a multicenter mechanism to study this rare disease or to perform therapeutic trials. The Acute Liver Failure Study Group was developed to answer this need. Tissue and serum samples as well as detailed epidemiologic and clinical data have been collected since January 1, 1998, at 14 sites around the US. Our results suggest that 50% of acute liver failure in the US is currently due to toxicity of pharmaceutical agents, both prescription and non-prescription drugs. Data concerning the use of transplantation and the outcome of ALF are now available. Existing scoring systems used to determine the need for liver transplantation have been tested in the patient group. Serum samples have been analyzed for new prognostic indicators and to identify possible candidate viruses in those for whom a causal agent cannot be identified. We also initiated a pilot study of the use of N-acetylcysteine for the treatment of ALF not caused by acetaminophen. Thus, the group has already provided several new insights into this condition, and has put in motion the mechanism for conducting controlled, blinded, and randomized studies of this important condition. The present proposal is to extend the study for an additional
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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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four years, plus one additional year for data analysis, and to expand the ALF Study Group to include 21 adult centers, while adding pediatric patients at 18 sites. Our current aims are similar to our previous ones: to gather further important clinical data and specimens for analysis and study, and to continue the N-acetylcysteine trial to its completion. The overall goal is to apply modern clinical, epidemiological and virological techniques to the study of this rare but devastating illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACCESS OF BLACK PATIENTS TO LIVER TRANSPLANTATION Principal Investigator & Institution: Reid, Andrea E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 29-SEP-2005 Summary: (adapted from the application) Orthotopic liver transplantation is the treatment of choice for selected patients with end-stage liver disease (ESLD). Unfortunately, liver allografts are a scarce resource. The disparity between the supply and demand for donor livers creates a potential for bias in the selection of organ recipients and the allocation of available organs. There is evidence that liver transplants are less available to blacks that to whites, despite a higher burden of ESLD, and higher rates of death from ESLD among blacks. Several small studies have suggested that barriers do exist for black patients with ESLD, but these barriers have not been defined. The overall goal of this grant is to determine what and where the barriers to transplantation are for black patients with ESLD. We will examine two components of the pre-transplant process in this study. We will focus on the referral process from the physician to the transplant center, and on patient perceptions of liver transplantation and the transplantation process. The specific aims of our study are: 1) To compare the referral rates for liver transplant evaluation and the overall clinical outcome in black and white patients with ESLD who were treated at three urban hospitals in Boston between 1994 and 1998, and 2) To determine if there are racial differences in knowledge and preferences about liver transplantation among patients with chronic liver disease. We will perform a retrospective cohort study of black and white patients with ESLD to determine if there are different rates of referral for liver transplant based on race. We will examine the clinical, financial, social, socioeconomic, and demographic factors that influence the rates of referral for liver transplant evaluation for these populations. We will also test the hypothesis that patient knowledge, attitudes and preferences about liver transplantation vary according to race and may influence the willingness of patients with ESLD to accept a liver transplant. To accomplish this, we will conduct a survey of a racially diverse group of patients with chronic liver disease. We will develop an appropriate instrument during the course of this grant, validate and pre-test it, then administer it to our study cohort. Advanced-level coursework in clinical epidemiology, biostatistics, survey development, and outcomes will also be a critical element of this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADULT TO ADULT LDLT COHORT STUDY Principal Investigator & Institution: Shaked, Abraham; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2009 Summary: (provided by applicant):The aim of this proposal is to demonstrate that the group of physicians and scientists at the Liver Transplant Program of the University of
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Pennsylvania has the interest, infrastructure and resources to participate in the Living Donor Liver Transplantation (LDLT) Cohort Study among adults awaiting transplantation. Progress in the care of patients suffering from end stage liver disease has been hampered by the limited availability of donor organs for transplantation. Adult to adult LDLT is expected to significantly expand the donor pool and provide numerous organs to be transplanted into designated recipients. The initial results are encouraging, however, there are many questions related to donor and recipient outcomes and whether better management of these patients can improve these results.A prospective mutli-center study of LDLT in the adult setting is expected to: 1. Collect and analyze data that will assist in the establishment of reliable criteria for donor selection, examine operative techniques that are associated with the best short and long term outcomes, and recommend methods for long-term follow up of the donor's physical and psychosocial well being. 2. Determine recipient outcomes when compared to the cadaveric setting and study whether results are affected by preoperative selection and preparation, operative techniques, and the interrelationship between regeneration and immune response. 3. Study the effects of LDLT on clinical practice and socioeconomic issues in transplantation. Success in addressing these problems through a national collaborative network will depend on the scientific and operational performance of the centers involved in the consortium. The Penn Transplant center is committed to participate in these collaborative efforts, and contribute to the research efforts that are aimed at better understanding of medical and surgical issues of LDLT.Our proposal is divided into three sections. Section one: A description of the resources and participation of the team of physicians at Penn Transplant Center. Section two: A description and strategy for the development of a comprehensive database. Section three: Two research proposals describing a four year research effort to identify: a. the interrelationship between the regenerative process, graft function, alloimmune response. and b. the biopsychosocial impact of LDLT on donors and recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADULT/PEDIATRIC MULTIPLE ORGAN FAILURE REGISTRY Principal Investigator & Institution: Offner, Patrick; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002 Summary: Project I-A (Adult Trauma Registry) and Project I-C (Pediatric Trauma Registry) will serve as the clinical foundations upon which all our other projects within our Trauma Center will be based. The constructs of early dysregulated systemic inflammation (Projects II, III, IV, V, VI, VII and VIII) following injury and the two-insult model of MOF are now well recognized, and have served as a framework for our predictive models of MOF. Risk factors for MOF can be categorized as follows: 1) tissue injury severity, 2) shock or ischemia-reperfusion, 3) severity of the inflammatory response, 4) host factors (including age, gender and co- morbidity), and 5) other factors (early blood transfusion, infections, secondary operative procedures)(with Project IX). Using various measures to quantify each risk category, MOF could be predicted as early as 12 hours following injury. Much of this work has regarded MOF as a dichotomous outcome. Recently, however, the view of MOF as a continuous spectrum of multiple organ dysfunctions has been emphasized. We hypothesize the following: 1. MOF is the result of dysregulated inflammatory response characterized by early systemic hyperinflammation and delayed immunosuppression; 2. Determinants of post-injury MOF can be identified and quantified; thereby allowing its early prediction after injury. Our specific aims are 1, To examine and quantify postinjury MOF as a continuous
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spectrum of multiple organ dysfunctions; 2. To refine our measurement of the MOF risk factor categories; 3. To examine the effects of other events on the occurrence of MOF, specifically blood transfusion (with Project IX), secondary operative procedures and hyperosmolar therapy (with Project IV). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL, DYSFUNCTION
ACETAMINOPHEN,
AND
LIVER
SINUSOID
Principal Investigator & Institution: Mc Cuskey, Robert S.; Professor and Head; Cell Biology and Anatomy; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: Acute liver failure and death due to the ingestion of normally therapeutic doses of acetaminophen (APAP), Tylenol, is a serious clinical problem in chronic alcoholics. The toxic response to APAP is hallmarked by hemorrhagic centrilobular necrosis and towering levels of serum transaminases which are preceded by centrilobular microvascular injury and congestion. Little is known about the pathophysiology of this early microvascular lesion, which is suspected to be important in the progression of magnitude of the subsequent parenchymal injury. We propose to study this aspect of the toxic response of the liver to APAP and its potentiation by alcohol bringing. The later is a growing and serious problem, especially on college campuses, but is pathophysiology has received little experimental attention. Preliminary data strongly suggests that alcohol binge drinking significantly increases the susceptibility of the liver to injury by APAP. The hypotheses to be tested in mice are: (a) APAP elicits alterations in the hepatic microvascular in a dose dependent manner that precedes and potentiates parenchymal injury and that alcohol bringing increases the susceptibility of the liver to injury by APAP; (b) that sinusoidal endothelial cells (SEC) and their cytoskeleton are the principal sites of microvascular injury; and (c) that injury to SEC is related to changes in their intracellular levels of glutathione (GSH) and cytochrome P450-2E1 (CYP2E1) as well as mediators released from Kupffer cells and/or recruited inflammatory cells. High-resolution in vivo microscopy will be used to determine the dynamic spatial and temporal development of hepatic microvascular dysfunction. Light and electron microscopic examination of fixed specimens and isolated SEC will elucidate structural alterations that can not ve visualized in vivo. These will be correlated with changes in GSH, CYP2E1, pro-inflammatory cytokines, superoxide, nitric oxide in SEC, liver and plasma to gain clues to explain the responses observed microscopically. How inhibition of these mediators modifies the injury will further elucidate their role. The results should provide new information about the pathophysiology and mechanisms involved in the early microvascular injury elicited by overdoses of APAP associated with suicide attempts or therapeutic doses of APAP in abusers of alcohol and their contribution to the time course, progression, and magnitude of hepatic injury. A better knowledge of the hepatic pathophysiology of alcohol bringing also should result. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANDIDATES
ALCOHOLISM
TREATMENT
IN
LIVER
TRANSPLANT
Principal Investigator & Institution: Weinrieb, Robert M.; Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 22-SEP-1999; Project End 31-AUG-2004
Studies
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Summary: Alcoholism is the most common root cause of end stage liver disease in the United States. By the time cirrhosis with liver failure is diagnosed, there are often no viable alternatives to liver transplantation even for the then-abstinent alcoholic. Liver transplant surgery is costly and donor organs are scarce. Once selected for transplant, patients typically wait two years for an organ and must remain "medically and psychologically stable". Data from our studies indicate that 15 percent of listed alcoholic liver transplant candidates admit drinking - and we believe this may be an underestimate. Further, studies have shown that cirrhotic alcoholics who continue to drink have high rates of mortality. Once listed, alcoholic patients are typically referred off-site for alcohol treatment or to AA meetings. But, our research has shown that greater than 50 percent of alcoholic patients who received liver transplants never attended formal substance abuse treatment or AA. Based on the data from these pilot efforts and from the larger literature on promising therapies for alcohol dependence, we plan to test a modified and expanded version of Motivational Enhancement Therapy (MET) combined with case management techniques (STD-MET), for use in the treatment of alcoholics awaiting liver transplant. We will test this integrated alcohol treatment in a randomized controlled design comparing two samples of 100 listed alcoholic liver transplant patients, each receiving supplemental treatments for their alcoholism over a six month period while listed. Both groups will receive standard referral to AA and community treatment. One group will receive on-site, integrated STD-MET while the second group will receive an equal number of sessions, on-site, viewing alcohol educational videos (STD-VID). Hypotheses: 1.During the pre-transplant "wait list" period - patients receiving STD-MET will show better engagement into the liver transplant regimen, reduced drinking and better general function than patients assigned to (STD-VID). STD-MET group will show: a) greater compliance with appointments and medical regimen - measured by standard measures of attendance, medical status, recall and understanding of their medication regimen, b) more awareness and acceptance of alcohol, smoking and/or other drug problems - measured by the (SOCRATES) stage of change, c) more attendance at standard off-site alcohol treatment programs and AA meetings - measured by standard checks on treatment attendance as well as TSR from subjects and collaterals, d) greater and more lasting reductions in drinking, cigarette and other drug use - measured by urine screens, breathalyzer, self-report and collateral TLFB measures, e) lower levels of depression and anxiety - measured by the BDI, BAI and the ASI psychiatric scale every three months, f) less mortality and morbidity prior to organ transplant - than the STD-VID group. 2. For patients who ultimately receive a liver transplant - STD-MET patients will show better general recovery than patients assigned to the alcohol education video series STD-VID. The STD-MET will show: a) fewer complications during during hospitalization measured by standard surgical records, b) better general function at one- month post hospital discharge-measured by standard medical evaluation and ASI than the STD-VID group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BOUND SOLUTE DIALYSIS Principal Investigator & Institution: Patzer, John F.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): The American Liver Foundation estimates that one in ten people has some form of liver disease and that 26,000 people die each year from liver disease. In the year 2000, 18,137 people were listed for liver transplantation, only 4,934 cadaveric donor liver transplants were made, and 1,636 patients died while
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Liver Failure
awaiting transplant. A medical need for a treatment modality that can "bridge" patients to transplant or slow or reverse the progression of liver disease clearly exists. Even better would be a new standard of care treatment that can be easily employed by any hospital at early stages (Parson's encephalopathy grade 1 and 2) of liver failure that would retard or prevent progression to acute liver failure that requires OLTx. Bound solute dialysis (BSD), practiced heuristically by the MARS and Biologic-DT approaches, offers the potential of a new standard of care treatment modality. Improvements in such heuristic practice require a theoretical approach that encompasses the underlying thermodynamics and transport phenomena. Such an analysis indicates that BSD is both more robust and more easily employed than expected from the heuristic approaches practiced here-to-fore. Experimental observations follow the theoretical predictions. The objective of this research proposal is to expend upon the preliminary studies in order to define what is necessary to bring BSD to the status of an easily employed standard of care treatment for liver disease that can be practiced with minimal requirements by any hospital or clinic. This will be accomplished by expanding the theoretical approach to encompass other forms of BSD, experimental validation of modeling predictions, development of an animal model of chronic liver failure, and preclinical evaluation of the various modes of BSD with the animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD40-CD154 INTERACTIONS IN CRYPTOSPORIDIAL IMMUNITY Principal Investigator & Institution: Ponnuraj, Esther; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 31-JAN-2005 Summary: (Provided by the applicant): Cryptosporidium parvum (CP) causes prolonged and severe infections in humans with AIDS or mutated CD154 genes (X linked immunodeficiency with hyper IgM, or XHIM) leading to sclerosing cholangitis and liver failure. CP infects gut epithelial cells that normally end their lifespan engulfed by dendritic cells (DC) in the lamina propria. The hypothesis underlying this application is that 'a CD40 signal is necessary for CP to be killed by DC'. This hypothesis predicts that intact, viable, CP will reach the mesenteric lymph node (MLN) when there is no CD40-CD154 signal. The underlying hypothesis accounts for the requirement for CD4 T cells that express CD 154, and marrow-derived CD40+ cells, for mice to recover from a CP infection. It raises the question: do the CD154+ CD4+ T cells required to clear CP have to be CP-specific? We found that RAG-/- mice expressing transgenic T cell receptors (Tg) for ovalbumin (or cytochrome c) recover from CP infections. Our preliminary data will show that adoptively transferred DO11.10 T cells are activated in the MLN of CP-infected RAG-/- mice provided that they are in an MHC matched environment. Our Specific aim one will determine whether E aboutxAI3 transgenic mice can clear a CP infection. This approach tests the hypothesis that the loading of antigen peptides onto self-MHC is required for a CP infection to be cleared from the gut. Secondary approaches under Aim 1 will (a) test the hypothesis that transgenic CD4 cells clear CP infections only in the MHC environment in which they were selected. In lc the requirements for IL-12, B7 and CD28 for activation of Tg and wild type CD4 cells will be compared. Specific Aim two will test the hypothesis that lamina propria DCs require a CD40 signal to degrade the proteins and nucleic acids of endocytosed CP and epithelial cells. These aims are selected because they address issues critical for under- standing immunity to CP and the immunopathology that results when an infection is not eradicated. Mechanisms established in CP infections are likely to be relevant to other important intracellular pathogens, particularly Microsporidia and Toxoplasmah sp. The
Studies
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results will be important for immunodeficient humans chronically infected with the parasite. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL VOLUME REGULATION IN NEURONS AND GLIA Principal Investigator & Institution: Alvarez-Leefmans, F Javier.; Professor; Physiology and Biophysics; Wright State University Colonel Glenn Hwy Dayton, Oh 45435 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAY-2007 Summary: (provided by applicant): Volume control is one of the evolutionarily oldest cellular homeostatic functions. It appeared when macromolecules were encased within a semipermeable plasma membrane, creating Donnan forces that tended to produce colloid-osmotic swelling. Animal cells lack rigid cell walls and are permeable to water. They evolved mechanisms for maintaining volume constant in the face of the Donnan effect, thus preventing osmotic swelling and lysis. Failure of these mechanisms compromises structural integrity and constancy of the intracellular milieu, causing osmotic disturbances in organ function that may be lethal, such as brain edema. Brain cells face unique and potentially severe challenges for cell volume homeostasis. Net accumulation or depletion of solutes may occur in neurons and glial cells as a consequence of neurotransmitter actions and nerve impulse activity, or in pathological conditions such as ischemia, trauma, seizures or metabolic disorders. Our long-term objective is to understand the mechanisms underlying cell volume control under normal and pathophysiological conditions in nerve and glial cells. The present proposal uses an in vitro model, at the single-cell level, to study mechanisms underlying short-term changes in cell water volume, intracellular pH, Ca2+ and organic osmolytes, elicited in neurons and glial cells by exposure to ammonia (NH3) and ammonium (NH4+). The clinical implications of this research stem from the fact that millimolar concentrations of NH3/NH4+ in arterial blood (hyperammonemia) are a key factor in producing brain edema characteristic of acute liver failure, a condition that may occur as a complication of viral hepatitis, toxic drug reactions, and some metabolic diseases. The pathogenesis of this edema is not understood in spite of being the main cause of death in acute liver failure. The short-term changes produced by NH3/NH4+ probably precede or cause the long-term changes occurring in brain tissue following acute hyperammonemia The proposed studies are as relevant for basic research as they are for pathophysiology; although the reciprocal interactions between pH1 and volume regulatory mechanisms have been recognized, concurrent measurements of pHi and cell water volume are lacking. To approach these issues we developed and validated optical methods based on fluorescence imaging and photometry, with unique time resolution (less than 1 second) and sensitivity (about1 percent), to measure simultaneously, in a single cell, changes in pHi (or [Ca2+]i) and water volume. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR ENGINEERING OF HEPATOCYTE CELL LINES Principal Investigator & Institution: Fox, Ira J.; Professor; Surgery; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 30-NOV-2006 Summary: (provided by applicant): Liver cell transplantation could potentially be used to treat liver failure and liver-based metabolic diseases. Unfortunately, the number of human livers available for hepatocyte isolation and transplantation is limited by competition for use in whole organ transplantation. A potential alternative to the
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Liver Failure
transplantation of primary hepatocytes would be to use a clonal cell line, which would provide the advantages of availability, uniformity and sterility. Such cells could be grown in unlimited number and at far less cost compared to isolated primary hepatocytes. We hypothesize that human hepatocytes can be conditionally immortalized and engineered to be safe for transplantation in the treatment of liver diseases. Rat hepatocyte cell lines have been generated that are capable of reversible immortalization by site-specific excision of an introduced SV40 T antigen using the loxP/Cre system. Such reversibly immortalized hepatocytes can correct liver function in animal models of acute and chronic liver failure and liver-based metabolic diseases. This proposal will assess whether reversibly immortalized human hepatocytes can be generated that can successfully integrate into the liver parenchyma of Rag2-/- mice following transplantation through the portal circulation. Studies will also examine whether reversibly immortalized human hepatocytes can function to correct the physiologic abnormalities associated with chronic liver decompensation in cirrhotic rats. In order to avoid the need for viral gene transfer technologies, we will also determine whether loxP/Cre generated reversibly immortalized human hepatocytes can be induced to undergo recombination using a TAT-Cre fusion protein. Finally, this proposal will evaluate the tumorigenic potential of loxP/Cre generated human hepatocytes. Evidence of alterations in tumor suppressor mechanisms will be assessed and transformation assays will be used to directly measure the tumorigenic potential of pre- and postexcision immortalized human hepatocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR IMMUNITY TO HEPATITIS C VIRUS IN HIV Principal Investigator & Institution: Graham, Camilla S.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Provided by Applicant) The epidemics of HIV and hepatitis C virus (HCV) infections meet in individuals with parenteral exposure to blood, including injecting drug users (IDU) and persons with hemophilia, where rates of coinfection range from 60-90 percent. Coinfected individuals have a significantly increased risk of progression to end-stage liver disease, though mechanisms by which HIV modifies the course of HCV are poorly understood. It is paradoxical that HIV, an immunosuppressive state, leads to an accelerated progression of liver disease, and that HAART is associated with liver failure as well. Our central hypothesis is that both peripheral and intrahepatic HCV-specific cellular immune responses are qualitatively and quantitatively different in patients coinfected with HIV compared with those with HCV monoinfection, and that this is not solely a function of the degree of immunosuppression. Our goals are to determine whether coinfected individuals have an altered cellular immune response to HCV, to determine if immune reconstitution impacts HCV-specific cellular immunity, and if cellular immune responses to HCV are associated with improved outcome with anti-HCV therapy. To address these hypotheses we are examining HCV-specific cellular immune responses in three groups: 1) individuals with HCV/HIV versus HCV alone, 2) individuals with HIV/HCV prior to HAART and during immune reconstitution, and 3) individuals with HIV/HCV who are entering a protocol of interferon-ribavirin therapy. We are using ELISPOTS to characterize secretion of interferon-gamma, tumor necrosis factor alfa, and interleukin-10 at the single cell level in peripheral mononuclear cells and liver-infiltrating lymphocytes in these populations. We are complementing these functional assays with flow cytometry to phenotypically characterize lymphocyte populations. Determining alterations in cellular immune responses to HCV in
Studies
15
individuals with HIV may help us to understand the pathophysiology underlying the accelerated progression of severe liver disease as well as help define subgroups of persons with HIV who may benefit from treatment of hepatitis C. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHIMERIC HEPATITIS C VACCINE VECTOR Principal Investigator & Institution: Nunberg, Jack H.; Director & Professor; None; University of Montana University Hall 202 Missoula, Mt 598124104 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Over 170 million persons are infected with Hepatitis C virus (HCV) and are at risk for liver failure and hepatocellular carcinoma. HCV is an enveloped RNA virus in the Flaviviridae family, which also includes the Flavivirus and Pestivirus genera. Molecular analysis of these latter genera has been facilitated by the ability to manipulate the complementary DNA genomes of these RNA viruses and to generate infectious virions that can be analyzed in cell culture. Viable chimeric Flaviviruses can be readily generated, and those expressing the envelope glycoproteins of pathogenic Flaviviruses within the nonpathogenic background of the 17D vaccine strain of the Yellow Fever Virus (YFV) have been shown to be safe and effective live vaccines. Efforts to understand the HCV life-cycle and to develop antiviral drugs and vaccines have been hindered by the inability to grow the virus in cell culture or in small animal models. Although restrictions on the in vitro propagation of HCV include those related to the interaction of the viral envelope glycoproteins with cellular receptor(s), additional barriers may include those that arise during the intracellular trafficking and assembly of the virion proteins. In this Small Research Grant proposal, we describe pilot studies to utilize the backbone of the strain 17D YFV vector to express the HCV envelope glycoproteins and develop a robust in vitro system to study HCV structure, function, and immunology. Specific Aims are: (1) to generate recombinant strain 17D YFV genomes bearing the HCV envelope glycoprotein genes, and (2) to assess the structural integrity of the HCV envelope glycoproteins and the ability of chimeric virion particles to be assembled and secreted. We will determine whether the chimeric virions are able to infect human hepatocellular carcinoma cells. Recombinant genomes may serve as a source of native HCV envelope glycoprotein complex for biochemical analysis. If chimeric virions are assembled and secreted, then the HCV envelope glycoproteins may mediate entry into appropriate target cells. Viable chimeric viruses will enable the study in cell culture of HCV binding and entry, as well as virion assembly and morphogenesis, and may provide a starting point towards the development of an attenuated HCV vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CIRRHOSIS AND ITS COMPLICATIONS Principal Investigator & Institution: Garcia-Tsao, Guadalupe; Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The candidate, Dr. Guadalupe Garcia-Tsao, is Associate Professor in the Department of Internal Medicine at the Yale University School of Medicine. She has devoted her career to patient-oriented research (POR) in the area of cirrhosis and in complications. She has been involved in a wide range of POR, from descriptive studies to multicenter randomized clinical trials. Her studies in the area of varices, variceal hemorrhage, ascites and spontaneous bacterial peritonitis have made significant
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Liver Failure
contributions to the management of patients with cirrhosis, the sixth leading cause of death in the United States in individuals between the ages of 25 and 65, the productive years of life. She is recognized as a clinical research in the area of portal hypertension as attested by invitations to chair abstract selection committees and to serve as session moderator at important scientific meetings, as well as invitations to write editorials, review articles and to become panel member at international consensus panels. Ascites is one of the main complications of cirrhosis and portal hypertension and Dr. GarciaTsao's short tem goals are to focus on this complication. One of these goals is to implement a randomized trial comparing the transjugular intrahepatic porto-systemic shunt with serial large-volume paracenteses in the treatment of patients with refractory ascites. This multicenter trial, partially funded by a VA Merit Review, will analyze not only differences in efficacy but also differences in quality of life and cost, and the results can potentially change current standards of care for patients with cirrhosis. R. GarciaTsao's long-term career goals are to continue to perform POR focused on prophylactic therapy and identification of prognostic factors in chronic liver disease as well as furthering her training in health services research. Dr. Garcia-Tsao has devoted a great deal of effort toward mentoring beginning clinical investigators in POR, especially in her capacity as co-Director of the Liver Center's Clinical Core. Yale University is one of the major teaching and research institutions of the United States and as such has wellestablished research and educational resources that will continue to be utilized by the candidate. The proposed award will allow her to carry out her research and mentoring objectives successful so that she can continue to make significant contributions in the field of cirrhosis and its complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF A NOVEL BIOARTIFICIAL LIVER Principal Investigator & Institution: Rozga, Jacek; Arbios Technologies, Inc. 2331 Buckingham Ln Los Angeles, Ca 90077 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-NOV-2003 Summary: ARBIOS developed a novel hybrid bioartificial live r(HyBAL) to treat patients with liver failure of various etiologies. In the absence of any other alternative, such patients must receive a liver transplant or endure prolonged hospitalization. In treating acute liver failure it is critical to provide whole liver functions. It is believed that liver support at this level of complexity requires utilization of viable isolated liver cells. Our own argument, which dates back to the development of our first-generate bioartificial liver, is that a truly effective system should be a hybrid one, i.e., it should combine liver cell therapy and detoxification using sorbents (e.g., activated charcoal, exchange resin). The HYBAL is the first liver assist system in which these two functions are integrated in a single molecule. Depending on the cause of liver disease, severity of illness and deficiency of specific liver functions, these modes of therapy can be provided individually, simultaneously or sequentially. In addition, the HYBAL's basic commercially available kidney dialysis platform represents a major improvement in efficiency with a concomitant reduction in cost and complexity compared to other existing systems. The goal of this proposal is to validate the HyBAL concept. The prototype HyBAL devices will utilize matrix-anchored rat or pig hepatocytes and sorbents (charcoal and exchange resin particles). They will e perfused for 8 hours with plasma removed with pigs with surgically-induced fulminant hepatic failure(FHF). Changes in plasma levels of ammonia, urea, bilirubin and other liver-specific parameters will be monitored. In addition, the HyBAL will be challenged with exogenous ammonium chloride, galactose and lidocaine. In vivo, he ability of HyBAL to
Studies
17
support pigs with FHF will be examined. In both experimental settings, HyBAL devices from which either cell therapy or sorbents have been omitted, will be tested to determine the respective role of cell and sorption therapy in the overall HyBAL performance. PROPOSED COMMERCIAL APPLICATIONS: The National Center for Health Statistics (NCHS) reported that in 1999, over 250,000 patients underwent 340,000 hospitalizations due to acute liver failure; 43,000 patients died (7th leading cause of death). Based on these data, NCHS estimates that more than 200,000 liver support treatments are needed annually in the U.S. lone to keep liver failure patients alive until an organ becomes available for transplantation or the native liver recovers from injury ($1.5-billion market). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFERENTIATION OF BLOOD STEM CELLS INTO LIVER CELLS Principal Investigator & Institution: Sell, Stewart; Professor; Pathology and Lab Medicine; Albany Medical College of Union Univ Albany, Ny 12208 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2003 Summary: (Adapted from the investigator's abstract) The hypothesis that progenitor cells in the bone marrow (bone marrow derived liver progenitor cells, BMLP) can give rise to liver cells will be formally tested in vivo and in vitro. In specific Aim 1 we propose a series of six experiments in which bone marrow or liver derived stem cells are transplanted into recipients. These experiments will define: 1) The conditions which activate BMLPs in the donor. 2) The conditions which may increase the ability of the recipient to accept and to nurture BMLPs. 3) The relationship of BMLPs to liver derived liver progenitor cells. 4) The ability of an hepatoblast cell line to give rise to bone marrow precursors. 5) Optimal markers for detection of transplanted cells. Donor mice will include normal male, lacZ male and EGFP male mice. Donor cells in irradiated female recipients will be detected by the presence of Y-chromosome and B-gal or EGFP. In specific Aim 2, bone marrow or blood cells will be cultured, using conditions known to be selective for hepatoblasts, to determine if colonies with hepatocyte phenotype can be produced. In both Specific Aim 1 and specific Aim 2, bone marrow and blood cells will be isolated from both normal mice and mice following partial hepatectomy or after cocaine induced periportal injury, experimental models to induce hepatocyte proliferation or periportal liver stem cell proliferation, respectively. These manipulations are known to induce growth factors for hepatocytes and liver stem cells and may encourage liver determination of HSCs. In addition, attempts will be made to isolate "pre-progenitor" cells from the bone marrow or liver that may have multilinege potential. In vitro colonies will be identified morphologically and passaged for analysis of differentiation potential after transplantation, phenotypic expression, growth properties, response to differentiating stimuli, and ultrastructure. Similar in vitro studies will be done on human bone marrow and blood using reserve cell preparations from the bone marrow transplant laboratory, which would otherwise be discarded. If this project is successful, it would overcome a major hurdle in the possible use of hepatic stem cells for treatment of liver failure or ex vivo gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISTAL SPLENORENAL INTRAHEPATIC PORTAL SYSTEMIC SHUNT
VERSUS
TRANSJUGULAR
Principal Investigator & Institution: Boyer, Thomas D.; Emory University 1784 North Decatur Road Atlanta, Ga 30322
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Liver Failure
Timing: Fiscal Year 2002 Summary: This is a multicenter, prospective, randomized clinical trial to compare DSRS and TIPS for the management of variceal bleeding in patients with Child's Class A & B cirrhosis. The primary goal of both therapies is to achieve control of variceal bleeding by reducing pressure in the varice, and limit the risk of accelerating the development of liver failure, ascites, and hepatic encephalopathy. The study will randomize patients who have failed or are not candidates for endoscopic therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY IDENTIFICATION OF ADVERSE REACTIONS TO HERBS Principal Investigator & Institution: Bent, Stephen W.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 16-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Herbal products have gained widespread popularity in the United States, with up to one-quarter of adults reporting use of an herb to treat a medical illness within the past year. Although herbs are commonly perceived as safe and "natural," numerous serious side effects have been reported, including myocardial infarction, stroke, liver failure, end-stage renal disease, and death. Unfortunately, surveillance systems to detect side effects of herbal products are extremely limited. Most serious reactions to herbs (including Chinese herb nephropathy and kava-kava related hepatitis) have been identified through case reporting, an inefficient system of monitoring that captures only a small percentage of all adverse events and only after large numbers of patients have been exposed. Current monitoring systems can be described as "passive," since action is only taken after enough case reports accumulate to raise concern of a possible dangerous adverse reaction. This career development program will provide the applicant with mentored training and research experience to examine the ability of "active" systems to detect adverse reactions to herbs at an early phase, before severe clinical outcomes occur. After completing an extensive curriculum in pharmacognosy, pharmacoepidemiology, and the analysis of complex cohort data, Dr. Bent will conduct four research projects that address two specific aims. The first specific aim is to determine if secondary data analysis is able to detect associations between specific herbs and laboratory and clinical outcomes that may represent adverse reactions. This will be addressed by three studies that examine 1) associations in a completed randomized controlled trial, 2) associations in an existing patient database, and 3) a comparison of the sensitivity and specificity of the two methods. The second specific aim is to determine the ability of a prospective cohort study to detect associations between specific herbs and laboratory/clinical outcomes that may represent adverse events. A cohort of patients at high risk for herb-drug interactions (patients on long-term anticoagulation) will be established to determine if herbal product use is associated with poor control of anticoagulation or related adverse clinical outcomes. Ultimately, this research strives to identify improved methods for the early detection of adverse events, providing patients with a safer environment to achieve the potential benefits of herbal products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ECLS IN MULTIPLE ORGAN FAILURE Principal Investigator & Institution: Bartlett, Robert H.; Professor of Surgery; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274
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Timing: Fiscal Year 2002; Project Start 01-AUG-1980; Project End 30-JUN-2004 Summary: Over the last 25 years our laboratory research on extracorporeal gas exchange and perfusion (ECMO) has progressed from oxygenator design, through the physiologic response to ECMO, through the development of extracorporeal technology to safe, simple automated systems which can be used to support cardiac or pulmonary function for days. Clinical success with ECMO indicates that expansion to total mechanical extracorporeal life support (ECLS) is feasible, but expansion of the technology requires a solution to two problems: 1) anticoagulation and thrombocytopenia, and 2) multiple organ failure. Despite many innovative approaches to anticoagulation and new prosthetic surfaces, systemic heparin anticoagulation is still required for extracorporeal circulation. A new group of anticoagulants inhibit clotting at specific early stages of the cascade. We will evaluate inhibitors of Factor IXa and Xa, used systemically or on the surface. Nitric oxide, a potent inhibitor of platelet adherence and activation, can be incorporated into the plastic materials and ventilating gas in the ECMO system, eliminating surface thrombogenesis, platelet consumption, and systemic anticoagulation without affecting endogenous platelet function. This research will develop and characterize thrombosis prevention leading to prolonged extracorporeal circulation without anticoagulation or thrombocytopenia. This will allow extension of mechanical life support from weeks to months, and initiate new approaches to ECLS. The nonthrombogenic surface combined with high blood flow and a unique albumin-based hemodiafiltration system can extend mechanical life support to liver failure and sepsis. The significance of this research is to decrease the mortality from cardiorespiratory and multiple organ failure. By studying prolonged support in experimental animals we will improve our understanding of the mechanisms and treatment of multiple organ failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF VPA 985 AND PLACEBO IN TREATMENT OF HYPONATREMIA Principal Investigator & Institution: Robertson, Gary L.; Professor; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: END-STAGE LIVER DISEASE/PREVALENCE & TREATMENT VARIATION Principal Investigator & Institution: Bryce, Cindy L.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) The primary purpose of this proposal is to provide the applicant with means and structure for achieving two goals. The immediate goal is to evaluate the effect of gender, race and income on access to liver transplant services. The long-term goal is to gain independence as a health services researcher by developing methodological expertise in decision sciences and multivariate statistical modeling and research expertise in organ transplantation and health policy evaluation. The applicant will obtain further instruction in computer simulation, geographic information systems, and advanced statistical analysis; in addition, she will receive clinical education to better understand the liver transplantation process and overall delivery of patient care. This training will be provided through formal coursework,
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directed readings, seminars and conferences, a clinical preceptorship, and research. Most activities will take place at the University of Pittsburgh's School of Medicine, Graduate School of Public Health, and Center for Research on Health Care. The applicant's research project evaluates the role of gender, race, and income in determining access to liver transplantation and explaining variation in liver transplant rates. To date, most studies on access to transplantation have focused on renal transplant services; few researchers have studied hepatic transplantation because of serious data limitations. Whereas the federal government maintains a comprehensive database of persons with renal disease from the time they receive dialysis, there is no centralized, population-based registry for persons with end-stage liver disease (ESLD). Most information on ESLD patients is collected on liver transplant candidates by the United Network for Organ Sharing. The hypothesis of this project is that demographic and economic factors significantly affect early access to transplant services, namely referral rates to transplant centers and listing rates by transplant centers. To address this issue, better information is needed. Therefore, the project will satisfy two aims: (1) develop and validate a population-based methodology for identifying and tracking a cohort of "transplant potential" patients with ESLD; and (2) estimate the effect of gender, race and income on movement through the transplantation process. This project will collect new information on patients with ESLD and combine it with existing data resources made available through The Optimal Timing of Liver Transplantation Project (AHCPR, R01 HS09694-02). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENGINEERED 3-D HUMAN LIVER TISSUE FOR HEPATITIS STUDIES Principal Investigator & Institution: Naughton, Brian; Regenemed, Inc. 4468 Saratoga Ave San Diego, Ca 92107 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): The Hepatitis C virus (HCV) is a leading cause of liver disease for which current treatments are inadequate. Worldwide, 170 million are infected with HCV and the disease is projected to kill more people than AIDS within a few years based on a death rate that is likely to triple in the next 20 years. HCV infection of the liver progresses to cirrhosis followed by hepatocellular carcinoma and ultimately liver failure, and is the leading reason for liver transplantation. Such infections have become an increasingly appreciated public health problem, especially because current treatment modalities are inadequate. The current standard of care employs a combination of interferon-a and ribavirin, but only half of the patients treated show a sufficient antiviral response. Thus, clearly there is a need and market for better therapies. A critical prerequisite for identifying and developing better therapies for viral hepatitis is the availability of convenient model systems capable of supporting efficient authentic viral replication. Unfortunately, to date the only non-human animal models are the chimpanzee and, with a variety of severe limitations, an immunodeficient xenotransplant mouse model. The great expense, and non-physiologic and low replication levels, respectively, associated with these animal models place great practical limits on their usefulness for rapid and efficient drug discovery and development. The availability of engineered human liver tissue capable of supporting viral infection would be relatively inexpensive, convenient, and ideal for the evaluation of novel antiviral therapies and the study of HCV and other virus-related pathology. This proposal seeks to leverage patented breakthrough technology in the field of engineered, 3-dimensional liver tissue into a novel platform for molecular virology and antiviral
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development. Keys to the success of this technology include its scalability, reproducibility, and an established ability to yield liver tissues far exceeding previous attempts at organ engineering. We seek to determine whether the engineered tissues can be infected with an efficient hepatitis virus capable of high-level replication and for which highly sensitive and specific detection reagents are available, namely hepatitis delta virus (HDV). We will then extend the potential of this core technology by determining the level of hepatitis C virus (HCV) infection and replication supported by these tissues. Engineered liver tissues will be inoculated with HDV or HCV infectious serum, or transfected with RNA transcribed from an infectious clone. Immunohistochemistry, immunoblot analysis, RNA genome replication by strandspecific northern blots, and de novo produced virus release by serial passaging and quantitative PCR analyses of the media supernatant will determine if infection and replication have occurred. The project detailed in this proposal is designed to test the above hypotheses and translate the results into a valuable new model system for studying viral hepatitis, generating virus for research use and the development of antivirals. Future indications include a unique and invaluable reagent for studying many key aspects of these viral life cycles, their associated pathogenesis, and novel approaches to antiviral therapy, including determination of the infection potential of subsets of hepatic cells, as well as other liver diseases such as non-alcoholic steatohepatitis (NASH), alcoholic hepatitis, hepatic fibrosis, and hepatocellular cancer (HCC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENZYMATIC DIFFERENCES AMONG HEPATITIS C VIRUS GENOTYPES Principal Investigator & Institution: Frick, David N.; Biochem and Molecular Biology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Almost one in every fifty-five Americans have been exposed to the Hepatitis C Virus (HCV), but most are unaware of their infection because the virus causes few acute symptoms. If left untreated, the majority of HCV infections lead to chronic active hepatitis that eventually progresses to cirrhosis, cancer, or liver failure. Current therapies involving the drugs interferon and ribavirin are costly and produce debilitating side effects, frequently worse than the symptoms produced by HCV itself. Newer treatments are, however, quite effective against certain viral genotypes. This proposal will examine the HCV proteins most directly involved in viral replication, the NS3 Helicase and NS5B polymerase, as putative targets for the drug ribavirin and as targets for new antiviral agents. In addition to its established role as a modulator of the immune system, ribavirin has been proposed to eliminate viruses as a mutagen or through direct effects on viral replicative proteins. One popular hypothesis states that ribavirin's enhancement of the already high HCV mutation rate leads to a catastrophe of errors and subsequent virus elimination. Here, ribavirin effects will be examined in vitro, in enzyme assays, and in vivo, using a novel HCV replicon that should allow the assessment of replication fidelity. To attempt to relate ribavirin effects to genotype-specific drug response, all experiments will be repeated with the three most common American HCV genotypes, two that normally do not respond to therapy (la and lb) and one that frequently responds to therapy (2a). The polymerase and helicase proteins from each genotype will also be characterized to define conserved and divergent properties. A rigorous biochemical approach will be used to define enzyme differences because sequence data alone does not accurately predict protein structure or
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function. Preliminary data show that different genotypes encode enzymes with markedly different properties, hampering current rational drug design efforts. Structure-based site-directed mutagenesis will be used to determine the genetic basis for HCV enzyme variability. The biological consequences (i.e. replication rate, fidelity, protein expression) of HCV genetic variation will then be analyzed in a replicon system. The delineation of genetic variations responsible for certain phenotypes might allow the prediction of patient response to current or future HCV therapies, and the clear identification of conserved HCV enzyme properties will aid future HCV drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Gershwin, Merrill E.; Professor; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Primary biliary cirrhosis (PBC) is an enigmatic autoimmune disease characterized by female predominance, high titer anti- mitochondrial antibodies (AMA), small bile duct destruction, and liver failure. Our group was the first to clone and identify the mitochondrial antigens, a family of phylogenetically conserved 2- oxo acid dehydrogenase proteins recognized by T and B cells in PBC. In addition, recent data has provided us with the basis for the following working hypotheses. We submit that PBC is most likely the result of an inappropriate or malcontrolled response to an environmental (either chemical or biological) insult. The initiating insult in PBC could be either a urinary tract infection (UTI) or an exposure to halogen containing chemicals. In the case of UTI's, there are high degrees of homology between the mitochondrial proteins present in micro-organisms that characteristically cause UTI's and their eukaryotic (i.e. human) analogs. Alternatively, the liver-based metabolism of halogenated hydrocarbons as xenobiotics generates activated halogen containing intermediates that react to form halogen modified proteins. In both, UTIs and halogenated chemical exposures, the introduction of these foreign proteins may initiate an immunological response that results in the immune system inappropriately targeting self proteins. These insults, which appear to be necessary but are not sufficient to elicit an autoimune response, given their widespread occurrence, needs to occur in conjunction with other disease associated contributory factors (i.e. genetic background) to produce PBC. We propose to take advantage of our strengths, including a nationwide network of PBC researchers, to accomplish this goal. We will collect and analyze data on demographics (race/ethnicity, socio-economic status, place of birth), medical history, reproductive history (parity, birth outcomes/complications, fertility problems, oral contraceptive use), menstrual history (age at menarche, age at menopause, average cycle length, cycle regularity) and lifestyle factors (smoking, physical activity, occupation and occupational exposures) using a questionnaire that we have tested in a preliminary study of 201 patients and 171 unaffected siblings. The project data will be collected from a sample of 2000 cases from 17 medical centers around the country and an equal number of matched (on age, gender and residence) random-digit dialed controls. The proposed study would be the first comprehensive epidemiologic study of PBC to be conducted in the United States, and directed at testing our thesis in the hope of improving our understanding of this serious disease and potentially identifying preventive measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTION OF THE HEMOCHROMATOSIS PROTEIN Principal Investigator & Institution: Enns, Caroline A.; Associate Professor; Cell and Developmental Biology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 29-FEB-2004 Summary: The goal of the present application is to determine how the protein implicated in hereditary hemochromatosis functions to regulate iron transport across epithelial cell barriers. Hereditary hemochromatosis is a disease of iron overload leading to iron accumulation in specific organs over the life time of the individual. Excess iron damages organs and results in a variety of problems such as liver failure, adult onset diabetes, heart failure, arthritus and hepatoma. It is the most common inherited disease in people of European descent affecting approximately 1 in 400 individuals. Recently the gene for this disease was identified and the protein it encodes (HFE) found to be similar to major histocompatibility class I proteins. The sequence of the molecule gives little insight into its function. Data obtained for preliminary results and previous data suggest that HFE is a negative regulator of iron uptake and mutations in the gene cause a loss of function. One model would be that HFE regulates iron transport across epithelial cell barriers by sensing the iron saturation of the iron transport protein, transferrin on the basolateral side of the cell. Iron uptake from the basolateral side via the transferrin receptor then would regulate iron transport from the apical to the basolateral side of the cell by altering intracellular iron pools. The model will be tested by measuring transferrin-meditated and transferrin- independent iron uptake in cells expressing HFE and compared to cells not expressing HFE. The long term goal of these studies is to determine how the transport of iron is regulated in the body. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY FOR LIVER AND LUNG DISEASE Principal Investigator & Institution: Flotte, Terence R.; Professor; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002 Summary: The goal of this proposal is to develop recombinant adeno-associated virus (rAAV) vector transduction of hepatocytes as a strategy for gene therapy for alpha-1anti trypsin (AAT) deficiency. AAT deficiency is a common monogenic disease that can lead to pulmonary emphysema in most affected patients and, in addition, to liver failure in a significant minority of patients. AAT is the major serum serine protease inhibitor (serpin) in humans; individuals with deficient (Z or S) or null AAT alleles can develop severe emphysema in early adulthood due to destruction of pulmonary elastin fibers by neutrophil elastase; cathespin G, and other neutrophil products. Current therapy to prevent lung disease in AAT- deficient patients consists of weekly intravenous infusions of a serum- derived AAT preparation, while in mice, rAAV-AAT vectors have been shown to express therapeutic serum levels after a single intramuscular injection. The efficiency of expression and secretion could be improved by targeting hepatocytes rather than skeletal myocytes, but earlier reports indicate that the efficiency of hepatocyte transduction may be limited to 5%. We propose to evaluate each of the rate limiting steps in hepatocyte transduction with 2 goals in mind. In the case of AAT lung disease, the goal is to increase the overall expression level, in terms of total output of AAT into the serum. The liver disease, however, is due to polymerization of the mutant protein, and so the goal will be to down-regulate expression of the mutant protein in as high a percentage of hepatocytes as possible. These two goals will be addressed in the following specific aims: 1. Delivery: The ability of rAAV-hAAT vectors
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to efficiently transduce hepatocytes after portal venous or systemic venous delivery will be assessed and enhanced, via the insertion of new targeting ligands into the rAAV capsid. 2. Molecular State of rAAV vector: The integration state of rAAV-hAAT in hepatocytes will be assessed serially over time using Southern blot hybridization and FISH to determine whether there is a limitation to the percentage of hepatocytes capable of long-term retention rather than short-term uptake of rAAV genomes. 3. Transcriptional Efficiency: The level and specificity of rAAV-hAAT expression within hepatocytes will be enhanced at the transcriptional level by optimizing promoter strength and by using a newly described system for amplifying tissue-specific expression by the use of a potent transcriptional transactivator. 4. Down-regulation of Mutant mRNA: Hammerhead ribozyme vectors will be designed to down-regulate the expression of the endogenous mutant forms of AAT and these will be tested in vitro and in vivo in transgenic mouse models. It is anticipated that these studies will also lay the groundwork for future clinical trials of rAAV-based gene therapy for AAT deficient patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HCV GENOMIC VARIABILITY IN HIV INFECTED HEMOPHILIACS Principal Investigator & Institution: Sherman, Kenneth E.; Associate Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: Hemophiliacs with symptomatic disease are multiply exposed to blood products including factor concentrates to correct the Internet clotting factor deficiencies. Prior to routine use of heat inactivation and screening of donor blood for specific viral pathogens, hemophilia patients were routinely exposed to, and infected with, viruses such as hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV). Cohort studies in hemophiliacs suggest several clinically and scientifically important findings that warrant further detailed investigation including; a) Liver disease progression may be altered in hemophiliacs infected with HCV with more rapid progression to liver failure and death; b) The source of infection from large pools of concentrate that were potentially infected by multiple discreet donors leads to a high risks of mixed infection represented by both genotype and quasi species heterogeneity; c) The HIV coinfected hemophiliacs may have different clinical outcomes and an altered immune response may facilitate our understanding of the underlying process of mutant virus selection, and the associated clinical outcomes. The overall goals of this proposal include the study and characterization of the genomic RNA of HCV in infected hemophilic patients with and without confection with HIV. In the retrospective Phase 1, we utilize the NCI Multi center Hemophiliac Cohort Study serum bank database to study the relationship between progression to decompensated liver disease and quasi species variability in the viral envelope hyper variable and core domain. Heteroduplex analysis will be used to rapidly screen samples from index patients and matched controls using samples longitudinally collected over a 10 year or longer period of time. Peptides will be produced from unique quasi species and these peptides will be evaluated for their function as CTL epitomes. Phase 2 involves the initiation and performance of a clinical intervention trial designed to determine variable kinetic response rates to PEG-interferon+ribavirin between hemophiliacs with HCV alone vs HCV/HIV coinfected subjects. Quasi species populations will be modified/cloned, sequencing will be performed to generate families of closely related core peptides that will be studied for their ability to bind and stimulate an immune response. Treatment nonresponders will be followed in a prospective cohort study for up to 3 additional
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years so that the evolution of the virus, and its associated immune response in this group can be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATIC DIFFERENTIATION OF CO-CULTURED ES CELLS Principal Investigator & Institution: Fair, Jeffrey H.; Surgery; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Candidate: The overall objective of this K18 Career Enhancement Award application is to provide the resources for enhanced training for the principal investigator so that he will become an independently funded surgical scientist who will contribute at a national level in stem cell biology leading to new cell therapies for liver disease. The principal investigator has enlisted the ongoing stem cell expertise of the following mentors: Terry Magnuson, PhD, Oliver Smithies, PhD, and Larysa Pevny, PhD, who are experts in stem cell and developmental biology. Retraining is required due to the length of time in the last seven years spent in clinical practice and patient-based research. There is a clear need to retrain in current recombinant DNA practices, advanced PCR analysis, and basic molecular biology in order to make the transition from clinical to basic science research. Environment: UNC-CH has a strong academic tradition and a commitment to training clinical scientists. The School of Medicine has a strong core facility including the Lineberger Cancer Center, the UNC Genomics Lab, the Confocal Microscopy Lab, and the Mouse Histology Facility to support all aspects of the basic stem cell research. Dr. Terry Magnuson, the stem cell mentor for this project, has an extensive track record of scientific success and is committed to the mentoring process necessary to carry this research to its fruition. Research: In this proposal, we will define the characteristics of embryonic stem cells in vitro as they differentiate in the hepatic lineage and co-culture with either embryonic cardiac mesoderm or hepatic progenitors. Our hypothesis is that Hepatic Progenitor (HP) cells signal Embryonic Stem (ES) cells to undergo tissue-restricted differentiation towards hepatocyte lineage in vitro that are capable of organ specific function in vivo. We will then investigate the biologic fate of these cells in vivo using a cellular transplant model of 2/3 partial hepatectomy. Growth factor culture conditions have been used to derive hepatocyte-like cells from ES cultures, but the in vivo function of the cells is unknown, and may be capable of producing malignancy. In addition, experiments in other organ systems suggest that manipulation of cell culture conditions alone is insufficient, but that cell-cell interactions are required in order to reconstruct and restore organ function. Furthermore, MHC expression, essential in the alloimmune response to liver transplants and the induction of tolerance, is not understood in ES cell development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPATIC NEUROCHEMISTRY
ENCEPHALOPATHY--NEUROPSYCHOLOGY
&
Principal Investigator & Institution: Thomas, Michael A.; Associate Professor; Radiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 05-AUG-1999; Project End 31-JUL-2004 Summary: (Verbatim from the Applicant's Abstract) Hepatic Encephalopathy (HE) is a well-recognized complication of cirrhosis. These patients display a variety of
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neuropsychological deficits as well as clinical and serum ammonia abnormalities. Subclinical hepatic Encephalopathy (SHE) is a subtler accompaniment of cirrhosis that is associated with neuropsychological abnormalities without significant neurologic findings such as asterixis. Although neuropsychological tests are the current standard for diagnosing SHE, the results are non-specific and reveal little about the underlying neurochemical processes. Cerebral Magnetic Resonance Spectroscopic (MRS) metabolic alterations and MRI signal abnormalities in the basal ganglia reveal a relationship between neuropsychological functioning and biochemical abnormalities found in patients with SHE. This study will involve collaboration among hematologists, radiologists, psychiatrists, MR physicists and neuropsychologists. We will identify a total of 60 liver failure patietns who have SHE and compare them to 60 healthy control subjects. These patients and healthy controls will undergo clinical assessment by hepatologists and neuropsychiatric evaluation by psychiatrists. Subsequently, they will undergo a comprehensive series of neuropsychological tests to characterize the nature of their neurocognitive deficits. Following these tests, all subjects will undergo MR Imaging and Spectroscopic (MRI/MRS) examinations. We aim to use 1H MRS to meare and compare absolute cerebral metabolite levels of myo-inositol, choline, and glutamine/glutamate in the frontal lobe, parietal lobe and basal ganglia of a matched group of SHE patients and healthy controls. The resulting MRS and MRI data will be quantitatively analyzed and correlated with the results of neuropsychological testing and clinical examination. Multivariate methods and correlational analysis will be used to test hypotheses regarding differences between SHE patients and controls. We hypothesize that myo-inositol will be decreased, glutamine/glutamate will be increased and choline will be decreased in patietns with SHE. We propose that these underlying biochemical abnormalities will be correlated with clinical, neuropsychiatric and neuropsychological aspects of SHE. If these relationships are found, they will provide an improved biochemical understanding of the underlined aspects of SHE as characterized y clinical and neuropsychological testing. This enhanced understanding of pathophysiology will improve our ability to diagnose and treat this condition, resulting in improved patient outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATIC TISSUE ENGINEERING Principal Investigator & Institution: Yarmush, Martin L.; Professor of Surgery; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 30-JUN-2007 Summary: (provided by applicant): Recent animal studies and clinical trials using bioartificial liver devices have shown great promise for the treatment for acute liver failure, and are providing valuable information on the problems and limitations of current ''1st generation" liver assist devices. It is becoming clearer every day, however, that more basic information of the effect of environmental parameters on hepatocellular function, as well as host-bioartificial liver interactions, is necessary before the concept of bioartificial liver becomes a reality available at reasonable cost. Our long-term objective is to help development of 2nd and 3rd generation devices, which are expected to be significantly more effective than currently available devices. In order to reach this goal, we require a better understanding of many critically important questions including: What is the minimum cell mass to support a patient? How long and well do hepatocytes function during plasma exposure? What are the most critical functions for patient survival? What is the impact of bioartificial liver treatment on the immune system and on subsequent liver transplantation? Answers to these questions will often not be
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obtainable using off-the-shelf tools, and will require the development of new experimental systems. Our main hypothesis is that there is a finite number of hepatic functions which are most critical for patient survival, that it is possible to significantly upregulate them in hepatocyte cultures (both at the single cell level and at the level of tissue), and as a result, reduce the cell mass required in the bioartificial liver. The specific aims are: (1) To use metabolic and genetic engineering approaches to enhance the performance of hepatocyte cultures in plasma; (2) To optimize the oxygenation and geometric configuration of hepatocyte co-cultures for plasma detoxification; (3) To investigate patient-bioartificial liver interactions and characterize the immunological response to extracorporeal perfusion with allo- and xenogeneic cells. These studies will provide the basic knowledge and technologies enabling us to develop the next generation of liver assist devices and speed up the translation of this promising modality to the bedside. The proposed studies will also provide basic tools useful in the development of other engineered tissues and organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATOCYTE GENE EXPRESSION UNDER HYPOTHERMIC STORAGE Principal Investigator & Institution: Kosari, Kambiz; Surgery; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 11-FEB-2002 Summary: (provided by applicant):L Recent advances in tissue engineering have made possible the creation of a xenogeneic bioartificial liver (BAL) as part of an effort to improve the survival of patients with acute liver failure (ALF). A major obstacle that faces this and most other tissue-engineered cell based products is the problem of storage. Potentially, hypothermic conditions may be utilized to allow the viable storage of the BAL from point of production to delivery. Indeed previous experiments using the BAL have shown that up to a 24-hour period of cold storage is feasible. However, longer storage time as well as improved viability and function is vital for its successful widespread application. Examination of the cellular mechanisms, specifically the gene expression patterns associated with the early phases of hypothermic damage, need to be examined in order to discover and subsequently test "protective" factors. New techniques in tissue culture and molecular/cellular biology make this goal attainable. We propose that exposure to hypothermia will cause an up-regulation in the expression of common motifs present in the cluster of co-regulated genes dealing with apoptosis and stress; furthermore, that these expression patterns are modified in the presence of "protective" factors. Our specific aims include establishment of gene expression patterns in cold-exposed mouse hepatocytes using microarray technology as well as suppression subtractive hybridization, studying modification of such patterns in the presence of a protective factor (sublethal pre-stress heat exposure), and finally, determination of the ideal cold-storage conditions in an "optimized" micro-BAL. We hope that our findings will facilitate prolongation of the cold storage period and improve the viability and function of the BAL. Even though the immediate benefit of this proposal will be for the BAL, we strongly believe that it will have significant implications for most xenogeneicbased, tissue-engineered artificial organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPATOCYTE GROWTH FACTOR MIMETIC FOR LIVER FIBROSIS Principal Investigator & Institution: Mento, Peter F.; Angion Biomedica Corporation Suite 100 Great Neck, Ny 11021
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Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Hepatic fibrosis, a disease affecting tens of millions of patients worldwide, is the liver scarring response that occurs in response to chronic injury from viral hepatitis B or C, excessive alcohol use, and iron overload, and often leads to liver failure and death. Despite the availability of antiviral and other therapies, most are ineffective in treating the underlying fibrosis and are associated with many side effects. Death from complications of liver fibrosis is expected to triple over the next decade as a result of the hepatitis C (HCV) epidemic and growing incidence of liver disease associated with obesity, so-called "non-alcoholic steatohepatitis" (NASH). Increasing numbers of patients are presenting to tertiary care centers in need of liver transplantation. Unfortunately, the number of cadaveric organs available for transplantation has plateaued and living related donor transplants have not shortened waiting lists. Hence, there is a critical need for potent antifibrotic therapies. Several recently published studies have demonstrated the therapeutic potential of exogenously administered HGF in the treatment of animal models of liver fibrosis. Endogenous HGF plays a key role in inhibiting fibrogenesis at least in part by downregulating TGFb1, the most potent factor for fibrogenesis. It may also act by its proliferative and anti-apoptotic actions. While administration of HGF holds promise as a therapeutic avenue for the treatment of liver fibrosis, protein-based therapies are notoriously difficult to administer because of potential immune responses, instability in solution, and cost-prohibitive production schemes. To overcome these shortfalls, low molecular weight compounds that mimic the activity of HGF would provide substantially improved therapeutic potential. Angion Biomedica Corp. has identified C6, a small molecular weight compound that mimics the effects of HGF both in vitro and in vivo. C6 inhibits renal cell apoptosis, promotes angiogenesis, prevents increased creatinine by renal ischemia and decreases the incidence of tubular necrosis in the mercuric chloride model of kidney failure. It is likely that C6 will have an antifibrotic effect in an animal model of liver fibrosis. These studies will provide the basis for more extensive Phase II studies to bring this potential therapy into clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATOCYTE PRECURSORS FROM MOUSE EMBRYONIC STEM CELLS Principal Investigator & Institution: Terada, Naohiro; Assistant Professor; Pathology, Immunol & Lab Med; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPTOCELLULAR RESPONSE TO CRYOPRESERVATION Principal Investigator & Institution: Toner, Mehmet; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JAN-1994; Project End 31-MAR-2007 Summary: (provided by applicant): Our overall goal is to develop long-term hepatocyte storage strategies that can be used for the treatment of liver failure. Although cell stasis is routinely achieved in nature by anhydrobiotic organisms through desiccation at ambient temperatures, the only existing strategy for long-term storage of mammalian cells is cryopreservation. Cryopreservation relies on cryogenic temperatures (typically < -80 degrees C) in order to halt all chemical reactions that result in cell death during
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storage. On the other hand, the pharmaceutical industry has made significant strides in storing proteinaceous drugs, liposomes, membranes, and viral particles in dry state using various small sugar molecules as stabilizers. Sugars, such as disaccharides, enter glassy phase at ambient temperatures at low moisture levels (approximately 5%) and minimize molecular mobility. Our hypothesis is that molecular mobility in the desiccated state needs to be completely prevented to stop deterioration of the cells and the cellular injury during dried storage. Stabilizers such as sugars, therefore, are needed to halt molecular mobility in order to achieve stability and long-term viability of cells in a dried state. We will test our hypothesis is four distinct but interactive Specific Aims. In Specific Aim #1, we will determine molecular mobility in dried cells in the glassy and near glassy state. In Specific Aim #2, we will investigate the mechanisms of cell death associated with cellular desiccation and to develop strategies to modulate these processes to improve survival. In Specific Aim #3, we will determine the stability of desiccated living cells and the key parameters affecting shelf life. In Specific Aim #4, we will test the efficacy of desiccated cells in small animal models of liver failure. The proposed studies will be carried out using several key sugars including trehalose, sucrose, raffinose, stachyose, and mixtures thereof. With the advancements being made in tissue engineering, cell transplantation, stem cell biology, and gene therapy, the clinical demand for effective long-term storage methods for cells and tissues will continue to increase for many different tissue types, including liver. Desiccation of mammalian cells is a very attractive alternative strategy that has the potential to truly disseminate these powerful technologies to medical centers, hospitals, and physicians' offices. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE RESPONSES IN ACUTE HEPATITIS C INFECTION Principal Investigator & Institution: Rosen, Hugo R.; Associate Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Approximately 2 percent of the U.S. population has HCV antibodies, and it is estimated that 10,000 people die annually of HCV-related complications including liver failure or cancer. Although new therapies have improved the rates of sustained response, the majority of patients are nonresponders to antiviral treatment, remaining at risk for disease progression. Although chronic HCV infection is very common, it is rarely identified acutely, and patients rarely seek medical attention until long after chronic infection is established. The very nature of this infection has made it extraordinarily difficult to study the early disease course except in the subset of individuals with definitive early symptoms and diagnosis. In this proposal we will direct our studies to the analyses of the specific cellular immune response to hepatitis C virus (HCV) infection as it occurs very early following acute infection in a communitybased cohort we have identified. The recent development of immunologic techniques that directly quantitate virus-specific lymphocytes ex-vivo will enable us to study the interactive mechanisms among virus, clinical disease, and host immune responses from the incubation phase. Detailed information of this stage of infection is clearly of value both in understanding the pathogenesis of the disease and potentially vaccine design. Our goal is to elucidate the cellular immune and virologic events in the initial stages of HCV infection that are likely to be crucial in determining self-limited infection versus chronic viral persistence and progressive liver injury. The specific aims outlined in this proposal include: To precisely examine the magnitude, kinetics, and breadth of HLA class I- and II- restricted cellular immune responses directed specifically against HCV
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and assess how these responses correlate with recovery versus chronic evolution; to characterize the temporal relationships between the level of HCV replication, its genetic diversity and the subsequent cellular immune response elicited by the viral infection. We propose to define how the host immune response shapes the kinetics of HCV replication. Furthermore, we anticipate that a subset of individuals who initially showed vigorous CD8+ T cell responses and control of viral replication will demonstrate abrogated HCV-specific immune responses over time and this will be associated with a rebound in circulating HCV viremia. In this subset of individuals, we propose to examine whether viral mutational events (yielding a high ratio of amino acid-changing substitutions to antigenically silent nucleotide base changes) in CD8+ T cell epitopes in viva has led to the generation of variant peptides that are no longer recognized by T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOGENICITY OF A XENOGENEIC BIOARTIFICAL LIVER Principal Investigator & Institution: Nyberg, Scott L.; Associate Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAR-2004 Summary: Liver failure is a serious problem that effects thousands of people in the United States each year. A new form of therapy, the bioartificial liver (BAL), is in development to provide liver function to patients with liver failure prior to transplantation or until recovery of the native liver. Results of preliminary trials of a BAL containing pig hepatocytes or human C3A cells have been encouraging, but improvement is still necessary. Cell death, for example, occurs during perfusion of the BAL and limits device function and the duration of therapy. The mechanism of hepatocyte death is poorly understood, and may result from immune-mediated injury. According to this hypothesis, immune activation during a first BAL exposure may cause an accelerated response during subsequent BAL exposures. Though the BAL contains a membrane to block contact of the patient's circulation and non-autologous hepatocytes in the device, pores in the membrane allow the release of antigenic material from the BAL and the entrance of molecular mediators of rejection from the patient. The following three hypotheses will be tested as specific aims of this study: (1) the death of hepatocytes in the BAL occurs by an immune-mediated mechanism; (2) The immune response of recipients to BAL therapy is increased during secondary exposures; (3) The immune response of the recipient adversely effects the functionality of the BAL. The immune response to the BAL will be characterized by changes in antibody titers, cellular activation, and cytokine expression in the recipient. The mechanism of cell death in the BAL will be determined by histological and biochemical examination of hepatocytes after BAL therapy. Hepatocyte viability and deposition of recipient proteins in the BAL will be measured and used to assess the effects of immune response in the BAL. The BAL will be tested in healthy dogs to provide a normal, primary immune response and to allow a second BAL treatment three weeks after the first treatment. Hollow fiber membranes with mean pore diameter of 200 nanometer and 5 nanometer (approximately 100 kD molecular weight cut-off) will be compared, since these pore sizes are relevant to current clinical trials of the BAL. A better understanding of the immune response in recipients will improve BAL therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPACT OF HEPATIC STEATOSIS ON HEPATITIS C Principal Investigator & Institution: Zacks, Steven L.; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This proposal will provide the candidate with the means of achieving the long-term goal of gaining independence as a clinical researcher in hepatology through a research proposal, structured mentoring, and methodological training. The candidate, Dr. Steven Zacks, is an Assistant Professor in the Division of Digestive Diseases. He and his mentors, Drs. Robert Sandler and Michael Fried, propose a combined didactic and clinical research experience, to foster Dr. Zacks' demonstrated interest in clinical research. As part of the training the candidate proposes to study the significance of hepatic steatosis on the highly variable natural history of hepatitis C (HCV). Because HCV can progress to cirrhosis with liver failure and death, it is important to target therapy to patients who are most likely to progress to cirrhosis. The candidate hypothesizes that HCV patients with steatosis on biopsy have nonalcoholic fatty liver disease in addition to HCV, leading to increased fibrogenesis. The specific aims of this study are to develop a well-characterized cohort of chronic HCV patients with and without steatosis on biopsy and to compare the prevalence of insulin resistance, markers of oxidant stress and fibrogenesis in chronic HCV patients with and without steatosis on biopsy. The proposed study will give the candidate valuable experience in the design of clinical studies, study management, data analysis, and manuscript preparation. The study will complement the didactic training at the UNC School of Public Health he has planned during the term of the award. The School of Public Health is a nationally recognized institution with an excellent graduate program in epidemiology. His sponsors have outstanding track records in mentoring and clinical research. Dr. Robert Sandler has a longstanding interest in training gastroenterologists to be outcomes researchers and will serve as the candidate's methodologic mentor. Dr. Michael Fried, an experienced clinical investigator in viral hepatitis, will be the candidate's clinical mentor. The candidate will have the wealth of clinical research resources at UNC available to him, including the NIH funded Center for Gastrointestinal Biology and Disease and the GI Epidemiology Group. The candidate has received formal training in the responsible conduct of research through the General Clinical Research Center. The UNC Department of Medicine is committed to providing the candidate with the protected time and resources to foster his career development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPROVED LIVER FUNCTION AND REGENERATION WITH A20 Principal Investigator & Institution: Ferran, Christiane; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Necrosis and apoptosis of hepatocytes are critical pathologic features associated with liver injury. Hepatocyte apoptosis is a feature of viral hepatitis, ischemic liver injury, sepsis, cholestasis, and a result of exposure to hepatotoxic substances such as ethanol, acetaminophen and cytostatic drugs. Massive hepatocyte apoptosis and necrosis result in fulminant hepatic failure (FHF). Only 14% of patients diagnosed with FHF recover with medical therapy. Orthotopic liver transplantation (OLT) has dramatically improved the fate of these patients (49% undergo OLT), yet 37% die while awaiting OLT. This gloomy picture is balanced by the unique capacity of the liver to regenerate. Hepatocyte replication leads to a full recovery
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of liver function and mass 1-2 weeks following surgical, viral or chemical hepatic loss. We propose that protecting hepatocytes from apoptosis and promoting their proliferation are two strategies that could beneficially impact FHF. Our preliminary data demonstrate that A20 promotes hepatocyte proliferation and is anti-apoptotic. A20 is part of the physiologic response of hepatocytes to injury. A20 is upregulated in hepatocytes by pro-inflammatory stimuli including TNF and LPS and functions to protect from TNF mediated apoptosis. Gene transfer of A20 to mice livers protects from lethality in the galactosamine and LPS (D-gal/LPS) model of toxic FHF. Adenovirus mediated expression of A20 in livers of BALB/c mice yields an 89% survival rate following administration of D-gal/LPS as compared to 15-20% in control mice. Mice expressing A20 maintain normal liver function as assessed by prothrombin time while controls suffer from a severe bleeding diathesis. Expression of A20 in the liver protects from lethality associated with a subtotal (87%) liver resection (LR). In this model, resection of 87% of the liver mass results in 100% lethality. In contrast, >60% of mice expressing A20 survive the 87% LR and demonstrate increased regenerative capacity as assessed by the number of PCNA (proliferating cell nuclear antigen) positive nuclei in the liver. These results qualify A20 as a critical gene involved in accelerating liver regeneration and promoting hepatocyte survival and function, even when facing extreme metabolic demands. These encouraging results prompted the submission of this proposal. Our specific aims are i) to dissect, in vitro, the molecular basis of the (1) antiapoptotic and (2) pro-proliferative function of A20 in hepatocytes and ii) to confirm that liver directed gene therapy using A20 will beneficially impact upon toxic, FAS-mediated and surgical experimental models of FHF. From a basic science standpoint, the in vitro work proposed will address the effect of A20 upon transcription factors and expression of genes involved in apoptosis, activation and proliferation of hepatocytes. This should unveil many unknowns in our understanding of hepatocyte biology and could lead to the discovery of novel therapeutic targets. From a therapeutic standpoint, validation of the beneficial effect of A20 in the murine in vivo models of FHF should set the basis for extending this approach to models of FHF in non human primates and potentially to clinical applications. The generation of novel safer and tissue specific viral vectors for gene transfer and the development of non-viral means of protein delivery to cells will facilitate clinical translation of A20 based therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDUCTION OF AP1 AND NFKB BY ETHANOL Principal Investigator & Institution: Brenner, David A.; Professor; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: Chronic alcohol use is the major cause of cirrhosis and liver failure in adult patients in the United States. In alcoholic liver disease, there is a strong correlation between the generation of free radicals and liver peroxidation projects and the induction of extracellular matrix proteins in fibrosis. Although the hepatic stellate cell (hsc, also called Ito cell or fat-storing cell) is the major cell that synthesizes the excess extracellular matrix proteins characteristic of cirrhosis, the mechanism of activation and perpetuation of the activated phenotype in the hsc is largely unknown. The activation of hscs is characterized by increases in both AP-l and NFkappaB transcription activity. These two transcriptional factors are induced by signaling processes that are responsive to oxidative stress. The underlying hypothesis of this proposal are that ethanol, acetylaldehyde, and/or LPS induce AP-l and NFkappaB in quiescent hscs, which is required for the initial activation. Subsequently, the ethanol-included cytokines,
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TNFalpha, TGFbeta, and/or IL-6 stimulate AP-1 and NFkappaB activity in the activated but not quiescent hscs. These hypothesis provide the foundation of a model on which the direct effects of ethanol provide the initial stimulus for signal transduction, which is perpetuated by the elevated cytokine levels ion alcoholic liver disease. The specific aims to be addressed in this proposal are: 1)to determine the effect of ethanol. acetylaldehyde, and LPS on AP-l and NF-kappaB induction in quiescent and activated hepatic stellate cells, 2)to determine the effects of TNF-alpha, TGF-beta, and IL-6 on the induction of AP-l and TGF- beta, 3)induction on the expression of collagen alpha1(I), 4)to assess the effect of blocking NFkappaB and APJ-1 activity in quiescent and activated hscs on proliferation, activation state, and collagen expression and 5) to assess AP-1 and NFkappaB expression in target cells in the brain and liver upon chronic exposure to alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERLEUKIN PROLIFERATION
6
AND
HUMAN
BILIARY
EPITHELIAL
Principal Investigator & Institution: Demetris, Anthony J.; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 28-FEB-2007 Summary: Cirrhosis, which is the 9th leading cause of death in the United States. It develops over a period of years to decades because chronic necro-inflammatory activity gradually transforms the normal architecture into nodules. This proposal is focused on the ductular reaction, which is important predictor of the development of cirrhosis and refers to the preferential growth of biliary epithelial cells over hepatocytes, recognized at the interface zone of diseased livers. By either favoring biliary epithelial cell or inhibiting hepatocyte proliferation some cytokines and growth factors hasten the development of cirrhosis, whereas others that stimulate hepatocytes (IL-6/gp130, HGF) and inhibiting biliary epithelial cell proliferation prevent architectural distortion and liver failure. In this proposal we plan to: a. Characterize the effect of IL6/gp130/STAT3 signaling, extracellular matrix and immunosuppressive drugs on biliary epithelial cell mitogenesis, apoptosis and maintenance of intercellular junctions, in vitro. b. Further characterize an experimental animal model of decompensated biliary cirrhosis in IL-6-/- mice after bile duct ligation using gene chip expression array analysis. Determine the role of p21 in hepatocyte proliferation and apoptosis during the development of cirrhosis and whether administration or exogenous recombinant growth factors, or transient transfection of vectors containing growth factors can influence the ductular reaction. c. Determine in humans, whether cytokine polymorphisms influence the susceptibility or the rate of progression of various chronic inflammatory liver diseases. The ultimate goal is to understand molecular mechanisms of differential biliary epithelial cell and hepatocyte growth control in diseased livers, which will serve as a rational basis for therapeutic intervention with cytokines and growth factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIVER INNATE IMMUNITY IN DRUG-INDUCED LIVER DISEASE Principal Investigator & Institution: Liu, Zhang-Xu; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): This proposal is a request for a Mentored Research Scientist Development Award (K01) from the National institute of Diabetes and
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Digestive and Kidney Diseases (NIDDK). The candidate has demonstrated significant commitment to research activities in the area of the liver immune response as it pertains to liver diseases. The K01 Award would enable the candidate to build upon previous research experiences in immunology and gain the research skills in the drug-induced pathobiology and molecular biology of primary hepatocytes and sinusoidal endothelial cells to develop an independent research career in the function of liver innate immunity in drug-induced liver disease. The candidate proposes to begin research in this field by focusing on the hepatotoxicity of acetaminophen (APAP), since it is a common cause of acute liver failure and serves as a prototype. There is growing evidence that inflammatory mediators released by nonparenchymal inflammatory cells contribute to drug hepatotoxicity. The abundance of natural killer cells (NK) and NK cells with T cell receptors (NKT) in the liver raises the question as to what may be the role of these cells in APAP-induced liver injury. Therefore, the overall goal of this proposal is to understand the function of liver innate immune system with the specific focus to elucidate the role of NK and NKT cells in APAP-induced liver injury. The candidate propose that drug metabolism-dependent events may initiate hepatocyte and sinusoidal endothelial cell damage and sensitize them to inflammatory mediators released from liver innate immunity, i.e., NK cells, NKT cells, macrophages/Kupffer cells, and the ultimate severity of drug-induced liver injury in vivo may depend greatly on the downstream participation of liver innate immunity and their interplays. Preliminary studies suggest that NK and NKT cells play a critical role in the progression of APAPinduced liver injury because elimination of these cells significantly protected mice from APAP-induced liver injury, as evidenced by reduced serum transaminase levels, centrilobular hepatic necrosis and accumulation of inflammatory cells in the liver. It is anticipated that the data obtained from this proposal will define the function of liver innate immune system and the molecular mechanism of liver injury and contribute to our understanding of the pathogenesis of drug-induced hepatotoxicity as well as develop novel therapeutic strategies for drug-induced liver diseases. This K01 award will provide the candidate with the opportunity to be trained with broad knowledge and skills in the molecular biology and pathobiology of primary hepatocytes and sinusoidal endothelial cells under the guidance of Dr. Kaplowitz and the center members at the outstanding environment of USC Research Center for Liver Diseases Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIVER REPOPULATION FOR LIVER INJURY AND GENE THERAPY Principal Investigator & Institution: Gupta, Sanjeev; Professor of Medicine and Pathology; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 20-JUN-1994; Project End 30-APR-2003 Summary: Our hypothesis has been that liver repopulation with parenchymal cells will help develop novel therapies and provide systems for addressing fundamental questions in liver biology. We and others have made significant progress in advancing these goals by identifying permissive conditions for hepatocyte survival and function, methods to increase the mass of transplanted hepatocytes, insights into hepatic gene transfer, and analysis of hepatic progenitor cells. However, more work is necessary before clinical applications of hepatocyte transplantation could be systematically analyzed. We propose a series of studies directed at further defining the safety of liver repopulation by analyzing transplanted cell biodistributions during manipulations to increase liver repopulation, amelioration of deleterious changes in the host liver emanating from cell transplantation, and mechanisms for improving cell engraftment in the normal or the diseased liver. We will begin to isolate and characterize progenitor
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cells derived from the fetal human liver and to isolate stable cell lines capable of differentiating into hepatocytes. To demonstrate the fate of progenitor human liver cells, we will develop novel genetic animal models, which will allow unequivocal analysis of transplanted cell survival, differentiation and human hepatocytes could be infected with hepatitis viruses to help develop models of disease. These systems will allow us and others to develop effective therapies and to address basic questions concerning mechanisms in hepatitis viral persistence and replication. In parallel bonafide animal models of acute and chronic liver disease in humans. Completion of our proposed studies will greatly advance fundamental knowledge of the ontogeny and differentiation of the liver, therapeutic potential of hepatocyte transplantation, and development of novel biological systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF CELLULAR TAURINE TRANSPORT IN BRAIN EDEMA Principal Investigator & Institution: Olson, James E.; Professor; Emergency Medicine; Wright State University Colonel Glenn Hwy Dayton, Oh 45435 Timing: Fiscal Year 2001; Project Start 15-APR-1999; Project End 31-MAR-2004 Summary: (Adapted from applicant's abstract): Cytotoxic brain edema is a serious complication of several clinical conditions including stroke, liver failure and traumatic brain injury and is characterized by swelling of astrocytes while volumes of neurons and other cells are relatively unaffected. It has been established that cell volume regulation in isolated astrocytes and neurons depends to some extent on the synthesis and transport of taurine. The central hypothesis of the application is that taurine is transported from neurons to astroglial cells during the development of cytotoxic brain edema, a process of regulation of neuronal volume. Based upon this hypothesis, it is proposed: (1) to determine swelling-induced changes in cell volume and taurine content of neurons and glia in hippocampal slices; (2) to test the proposal that taurine efflux from neurons is more sensitive and is distinct from that from astrocytes; (3) to characterize signal transduction pathways involved in taurine efflux in neurons versus astrocytes; (4) to examine volume regulation, electrophysiology and ion homeostasis in hippocampal slices exposed to osmotic edema. It is suggested that these studies will provide a better understanding of mechanisms of brain cell volume regulation under physiological conditions and the response of brain cells to pathological swelling, the knowledge of which will help in understanding cytotoxic brain edema in clinical states and in developing novel therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF DRUG INTERACTIONS AND REACTIVE METABOLITES Principal Investigator & Institution: Nelson, Sidney D.; Dean of Pharmacy; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term objectives of the research described in this project are to understand mechanisms by which the widely used analgesic/antipyretic, acetaminophen, interacts with other drugs, and to characterize at the molecular level enzymes involved in the interactions. This is important to avoid life-threatening hepatic necrosis initiated by N-acetyl-p- benzoquinone imine, a reactive metabolite of acetaminophen formed by several cytochrome P450s that metabolize many other drugs.
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Results of previous studies implicate CYP2E1 and CYP2A6 as major catalysts in the oxidation of acetaminophen to its toxic quinoneimine and non-toxic catechol metabolites, respectively, and inhibition/induction of CYP2E1 by other drugs, such as isoniazid and ethanol, can increase or decrease risk of hepatotoxicity caused by acetaminophen depending on the time of ingestion relative to consequences of ligand regulation of CYP2E1. We propose to continue our studies of P450s responsible for the oxidation of acetaminophen in the next grant period. The first Specific Aim of this proposal is to construct active site models of CYP2E1 and CYP2A6 that are consistent with the different product selectivities of these two P450 isoforms for the quinoneimine and catechol metabolites of acetaminophen. A multi-tiered approach will be used that incorporate the results of NMR paramagnetic relaxation studies, homology and CoMFA modelling, mutagenesis experiments, and studies with mechanism- based inactivators. The second Specific Aim is to assess the roles of CYP2E1, CYP3A4 and dysregulation of hepatocyte mitochondrial glutathione status in the market toxicity of acetaminophen in individuals who chronically consume ethanol. This interaction has been suggested to be the leading cause of acute liver failure in the U.S. The interactions is multifaceted and the proposed studies continue an evaluation of this interaction initiated during the last grant period. A rat model will be used to investigate the separate effects of changes in acetaminophen reactive metabolite formation clearance and hepatocyte mitochondrial GSH status on hepatocellular damage. A series of studies will be conducted in human volunteers to determine the contribution of CYP2E1 and CYP3A P450 isoforms to acetaminophen reactive metabolite formation in vivo at acetaminophen doses relevant to the interaction and the effects that moderate drinking of alcoholic beverages and starvation have on this clinical syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF MET-INDUCED HEPATOCYTES SURVIVAL Principal Investigator & Institution: Zarnegar, Reza; Professor; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Based on the results of our recent experiments, we hypothesize that one major function of Met protooncogene in the liver is to inhibit apoptosis in hepatocytes. We believe that one mechanism by which Met elicits an anti-apoptotic effect is via an interaction between Met and the death promoting cell surface receptor Fas, the net result of which is sequestration of Fas by Met and inhibition of the initiation of the Fasmediated apoptotic pathway. Another novel mechanism by which Met may modulate apoptosis involves direct inhibition of the executioners of the apoptotic pathway, namely the effector caspases (casepase- 3 and caspase-7), by a substrate suicide mechanism employing the cytoplasmic c-terminal tail of the Met protein. These interactions squelch the apoptotic command and thus promote cell survival. In Aim 1, we will determine the nature of the Met-Fas interaction and will map the structural domains in Met and Fas that are required for their association. We will address the biological relevance of Fas sequestration by Met and its contribution to hepatocyte survival, liver development, hepatic homeostasis and transformation using transgenic and knock out mouse models. In Aim 2, we will test the hypothesis that Met is a key target of the destructive action of the effector caspases (such as caspase-3) during apoptosis. This hypothesis is based on our findings that Met is essential for cell survival and because a perfect caspase cleavage site is present in Met's tyrosine kinase activation domain. Importantly, germline and sporadic mutations in this tyrosine kinase activation domain (in the putative caspase cleavage site that we have identified) have been
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reported. We will investigate the hypothesis that these mutations make Met refractory to caspase cleavage thus causing cells to be resistant to apoptosis and contributing to malignant transformation. In Aim 3, we propose to test the hypothesis that Met protein has evolved a novel mechanism to elude/inhibit the executioners of the apoptotic pathway, namely the effector caspases. We propose that caspase inhibition by Met is achieved through a substrate suicide mechanism involving the intracellular cytoplasmic end of the Met molecule. In this region, we have discovered the octapeptide sequence DNADDEVD. Since this peptide sequence harbors tandem perfect effector caspase cleavage sites (i.e. for caspase-3), we propose that during apoptosis this peptide sequence is cleaved by these caspases resulting in the formation of the tetrapeptide DEVD, a well-known potent inhibitor of caspase-3 and caspase-7. In Aim 4, we will test the hypothesis that the met gene is induced in response to cellular stress to protect cells from apoptosis and is a target of upregulation of NF-kappaB, a transcription factor known to be essential for hepatocyte survival during embryonic development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDIATORS OF INTERFERON-MEDIATED GENE EXPRESSION Principal Investigator & Institution: Horvath, Curt M.; Associate Professor; Center for Immunobiology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Treatment of cells with type I interferon (IFN) leads to transcriptional activation of genes involved in cellular antiviral effects, growth inhibition, and immune regulation. The study of IFN-mediated transcription is critical to treatment of chronic viral diseases including HIV, the causative agent of AIDS and Hepatitis C, the leading cause of liver failure and cirrhosis. Both viruses are endemic in the United States and IFN has been used in their treatment. The long term objective of my laboratory is to understand the mechanisms by which STAT and IRF transcription factors combine to produce the trimeric IFN-responsive transcription complex, ISGF3. The ISGF3 factor is a unique STAT-dependent transcription complex because the signaling phase is dissociated from the nuclear functions by an obligatory DNA binding subunit, IRF9/p48. Although the signal transduction pathways involved in activation of the ISGF3 trimeric transcription factor complex have been well studied, the mechanism of transcriptional activation is only poorly understood. The published literature and our own preliminary studies indicate that a fundamental transcriptional activation domain (TAD) for ISGF3 resides in the STAT2 C-terminus. Preliminary studies using IRF9STAT2 TAD fusion proteins that mimic ISGF3 transcriptional responses and recapitulate IFN biological responses have produced a structure-function map of this domain and have contributed to generating the hypothesis that the STAT2 TAD provides a protein interaction platform for several types of transcriptional co-activators. In support of this hypothesis, we have used a candidate-partner approach to identify a new transcriptional partner for STAT2 that is a subunit of the metazoan Mediator complex. Analysis of endogenous ISGF3 activity in STAT2 mutant-expressing cell lines will be carried out to connect specific STAT2 TAD regions with specific target gene expression patterns, biological responses, and promoter chromatin remodeling activities. The four proposed experimental aims will: (1) determine the functional significance of transcriptionally important STAT2 C-terminal TAD regions in a physiological context, (2) characterize the molecular mechanisms involved in STAT2 interactions with Mediator subunits, (3) determine the ability of ISGF3 to regulate promoter chromatin dynamics and map corresponding STAT2 C-terminal regions, and (4) identify additional
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protein partners for the STAT2 C-terminus. The proposed experiments provide a unique model system for the study of activated transcription, in which contributions of specific STAT2 TAD regions responsible for IFN target gene expression patterns, co-activator recruitment, and/or chromatin remodeling activities can be correlated with physiologically relevant IFN biological responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MESENCHYMAL STEM CELL THERAPY: A1 ANTITRYPSIN DEFICIENCY Principal Investigator & Institution: Verfaillie, Catherine M.; Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Alpha-l-antitrypsin (alpha1AT) is a plasma protein, produced in the liver that inhibits elastase, alpha1AT-deficiency is an autosomal recessive disorder that affects approximately 105 individuals in the US. Liver injury in alpha1AT-deficiency is caused by the hepatotoxic effects of mutant alpha1AT retained within the endoplasmic reticulum (ER) of hepatocytes, and emphysema by uninhibited proteolytic damage to elastic tissue in the lung parenchyma. Orthoptic liver transplantation is the only curative therapy for alpha1AT-mediated liver disease. If a reliable source of hepatocytes were available, they could conceivably be used to replace 20-25% of the host liver, elevating plasma levels of alpha1AT to greater than 10 muM, and preventing pulmonary toxicity due to alpha1AT-deficiency. We have identified multipotent adult progenitor cells, or MAPC, that can be cultured from human, mouse and rat bone marrow (BM). Single MAPC differentiate into mesodermal, neuroectoderm-like cells and functioning hepatocyte-like cells in vitro. MAPC do not form tumors when infused IV, IM or SQ, but differentiate in response to local cues into hematopoietic cells and epithelium of lung, intestine and liver. For MAPC derived hepatocytes to be suitable for therapy of alpha1AT, or other liver disorders, better characterization of the in vitro differentiation process will be needed. In addition, we will need to demonstrate that MAPC-derived cells function like hepatocytes in vivo. We propose three aims to determine whether MAPC-derived hepatocytes may be a source of cells to treat alpha1AT-deficiency mediated pulmonary and/or liver disease. Studies in SA1 will further demonstrate that hepatocyte like cells can be generated from bone marrow derived MAPC, and develop methods to select progenitors/precursors for hepatocytes generated during culture. Selection of such progenitors will serve two purposes: characterization of differentiation from pluripotent adult stem cells to hepatocytes, and generation of a potential source of cells for effective transplantation in liver disease. Studies described in SA2 that will assess all functions of mature hepatocytes in spheroid cultures should help confirm that hepatocytes generated from BM MAPC are similar to hepatocytes derived from primary liver. Studies in SA3 will establish whether MAPC themselves, MAPC-derived hepatocyte progenitors or mature hepatocytes can restore liver function in vivo, in the setting of hepatocyte cell death and in the setting of abnormal liver function but without liver cell death. This should lay the groundwork for future studies testing whether MAPC or MAPC-derived hepatocyte progenitors/hepatocytes can serve as a suitable source of cells for therapy of alpha1AT, a single gene defect associated with lung damage and/or liver failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MICHIGAN HEPATOTOXICITY CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Fontana, Robert J.; Assistant Professor; 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-2006 Summary: (provided by applicant): An increasing awareness of the importance of drug induced liver injury (DILl) has come from the large number of prescription drugs either being withdrawn or failing to gain regulatory approval due to hepatotoxicity. In addition, DILl has been identified as the leading cause of acute liver failure in the United States. However, the incidence and risk factors for drug, toxin, and complementary medication induced liver injury remain ill defined due to their unpredictable nature, varying clinical manifestations, and lack of diagnostic tests. Aberrant host immune responses, metabolic activation of the parent drug, and altered metabolite detoxification have been implicated in the pathogenesis of DILl but the molecular mechanisms involved in most cases remains unknown. The majority of DILl clinical studies have been uncontrolled, retrospective case-series involving small numbers of patients and individual agents. The primary aim of this proposal is to develop standardized instruments and methods to identify and characterize cases of drug, toxin, and complementary medication induced liver injury. Simple, reproducible causality assessment instruments will be developed and validated to provide more accurate case definitions. The secondary aim of this proposal is to develop a hepatotoxicity clinical research network that will prospectively enroll a large number of drug, toxin, and complementary medication induced liver injury cases as well as case controls that received the suspect drug but did not develop toxicity. A prospective casecontrol study design will help identify potential clinical, immunological, and genetic risk factors for DILl. Collection of clinical data, blood, urine, DNA, and liver tissue samples will allow for subsequent studies of the molecular pathogenesis of drug, toxin, and complementary medication induced liver injury and potentially help identify high risk individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MITOCHONDRIAL DEHYDROGENASES
SHORT
CHAIN
3-OH-ACYL-COA
Principal Investigator & Institution: Strauss, Arnold W.; Professor and Chair; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 20-AUG-1999; Project End 30-JUN-2004 Summary: Mitochondrial fatty acid beta-oxidation is the major source of energy in highly oxidative mammalian tissues and is essential for intermediary metabolism and production of ketone bodies in liver. Human genetic defects in fatty acid oxidation genes cause acute liver failure, a Reye's syndrome-like phenotype of hypoketotic, hypoglycemia; cardiomyopathy; skeletal myopathy; or sudden, unexpected childhood death. This pathway consists of four enzymatic steps catalyzed by 12 different nuclearly-encoded enzymes that are developmentally-regulated and tissue- specifically expressed. This proposal focuses on two enzymes catalyzing the third step, the short chain 3-hydroxy-acyl-CoA dehydrogenases (SCHAD). Aims 1 and 2 will examine the hypothesis that tissue-specific and developmental expression of the SCHAD-1 and -2 genes is coordinated with other fatty acid oxidation enzyme genes and involves nuclear hormone receptor transcription factors responsive to energy requirements and nutritional cues. Aim 2 will use the human SCHAD-1 gene and in vitro transfection and
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transgenic mice to locate critical regulatory sequences. Based upon the SCHAD-1 crystal structure and protein homologies, Aim 3 will determine structure-function relationships of SCHAD-1 of normal and mutant SCHADs after expression in bacteria to explore the hypothesis that SCHAD-1 and long chain 3-hydroxy- acyl-CoA dehydrogenase share common structural domains. Using the human gene sequences we have determined, Aim 4 will delineate SCHAD-1 or -2 mutations in children to examine the proposal that SCHAD deficiency and environmental stresses cause a Reye's syndrome-like phenotype of acute hepatic failure. Aim 5 will examine the effects of the three human SCHAD-1 mutations we have discovered on structure and function, the pathogenetics of SCHAD deficiency, to explore the hypothesis that SCHAD missense mutations result in rapid intramitochondrial degradation secondary to misfolding. Aim 6 is to define the phenotype of SCHAD-1 gene ablation we created in mice as a model of human disease, to examine the effects of environmental and drug (aspirin and acetaminophen) stressors on outcome and to similarly study an SCHAD-2 knockout. These studies will augment understanding of the pathogenesis of fatty acid oxidation disorders causing acute liver failure, cardiomyopathy, and sudden death in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MMP-9 MEDIATES CEREBRAL EDEMA IN FULMINANT LIVER FAILURE Principal Investigator & Institution: Nguyen, Justin H.; Mayo Clinic Coll of Med, Jacksonville Mayo Clinic Jacksonville Jacksonville, Fl 322243899 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Fulminant hepatic failure (FHF) is a life-threatening disease. The definitive treatment for FHF is a liver transplant. Unfortunately, 35% of all FHF patients and 62% of nonacetaminophen-induced FHF patients die within 48 hours after reaching stage 3 or 4 coma, while awaiting a transplant. Increasing this narrow therapeutic window would provide substantially more opportunities for these patients to be transplanted. One of the primary causes of death in these individuals is cerebral edema. The mechanisms responsible for cerebral edema in these FHF patients are poorly understood. Recent evidence from other laboratories has shown that matrix metalloproteinase-9 (MMP-9) may play a pivotal role in the development of cerebral edema in other disease states. For example, treatment with either MMP-9 synthetic inhibitors or anti-MMP-9 monoclonal antibodies has been shown to result in a significant reduction in the size of cerebral infarcts. Further, studies using MMP-9 knockout mice have shown a significant attenuation in cerebral edema following either cerebral ischemic or traumatic events. Based on these data we hypothesize that MMP-9 plays a critical role in the development of cerebral edema following FHF. Significant support for this hypothesis has come from two observations made in our laboratory. First, both proMMP-9 and MMP-9 are elevated in the sera of FHF patients and in rats with experimentally induced FHF. Second, in a pilot study, we have shown that treatment with an MMP-9 inhibitor (GM6001) results in an approximate 30% reduction in cerebral edema in rats with experimentally induced FHF. In this application, we specifically propose to: 1. To further determine if inhibition of MMP-9 by the MMP synthetic inhibitor GM6001 attenuates cerebral edema in rats with experimentally induced FHF. 2. To determine whether cerebral edema is attenuated in MMP-9 knockout mice following experimentally induced FHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODELING VIRAL AND T LYMPHOCYTE DYNAMICS Principal Investigator & Institution: Perelson, Alan S.; Staff Member; None; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2002; Project Start 19-APR-1991; Project End 31-MAR-2005 Summary: Mathematical modeling combined with experiment has led to increased understanding of the processes that underlie HIV-1 infection in humans and the development of improved therapies. Nevertheless HIV has not been eradicated from infected individuals and various reservoirs including latently-infected cells, virus trapped on folliculary dendritic cells (FDC), and virus in semen have been identified. This application proposes to continue the development of more realistic models of HIV infection with particular emphasis on events that occur in lymphoid tissue. The applicants propose to develop models that explicitly take into consideration infection in blood and tissue, the role of FDC, and possible incomplete penetrance of drugs into various cell populations and tissues. The primary health-related effects of HIV infection are consequences of CD4+ T cell depletion. Nevertheless, the population dynamics of T cells in vivo are poorly characterized. It is proposed to develop theory and analyze data from in vivo labeling studies that will help characterize the rates of proliferation and death of T cells in uninfected, HIV-infected, and HIV-infected individuals under potent antiretroviral treatment. Infection by hepatitis C virus (HCV) and hepatitis B virus (HBV) continue to cause liver failure and hepatocellular carcinoma in many infected individuals. Antiviral therapy for these agents lags behind developments in HIV. The applicants propose to use the modeling and analysis tools that they have developed for HIV to increase understanding of the in vivo kinetics of HCV and HBV infection and the effects of antiviral therapy. In addition to gaining basic understanding, this approach aims to put information into a practical setting, and the applicants hope to interact with clinical groups in the design and evaluation of new treatment protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR TRANSPORTERS
PHYSIOLOGY
OF
LIVER
FATTY
ACID
Principal Investigator & Institution: Stahl, Andreas; Palo Alto Medical Foundation Res Inst 795 El Camino Real Palo Alto, Ca 94301 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The liver is a central organ for coordinating much of metabolism and has a large capacity for fatty acid uptake. Considerable evidence has accumulated to show that in addition to a diffusional component, the intestine, heart, adipose tissue, and the liver express a saturable and specific long-chain fatty acid transport system. Identifying the postulated liver fatty acid transporter is of considerable importance, since both increased and decreased hepatic LCFA uptake have been implicated in diseases such as type-2 diabetes and acute liver failure. Investigators have found several membrane proteins that increase the uptake of LCFAs when overexpressed in cultured mammalian cells. The most prominent and best characterized of these are FAT/CD36 and fatty acid transport proteins (FATPs, solute carrier family 27). However, neither the better studied FATPs, FATP1 and -4, nor CD36 are expressed at appreciable levels in the liver. Therefore, we have identified FATPs that are expressed in the liver and have characterized their contribution to protein-mediated LCFA uptake and general energy homeostasis. We have identified two FATP family members, FATP5 and -2, as possible candidates for this role. FATP2 is expressed in liver and kidney, while FATP5 expression is liver-specific. The purpose of this proposal is to determine
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the contribution of FATP5 to hepatic fatty acid uptake. To accomplish this, we will determine the localization and regulation of FATP5 in the liver and generate animal models for loss and gain of FATP5 function. To this end, we have generated FATP5 null mice, which show reduced hepatic fatty acid uptake and diminished liver triglyceride content. We will use this unique model system to explore the role of liver LCFA uptake for energy homeostasis and the etiology of diseases, particularly of type-2 diabetes. Excessive liver TG accumulation is a well-described feature of the "metabolic syndrome" and may, in part, be responsible for insulin resistance and increased glucose levels. To evaluate FATP5 as a potential target for therapeutic intervention, we will test whether FAT5 null animals show reduced lipid accumulation, and increased insulin sensitivity in dietary and genetically induced models of diabetes. We will also test the hypothesis that the converse is true, by generating FATP5 transgenic mice, which may have increased liver LCFA uptake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTICENTER RANDOMIZED TRIAL OF DSRS VERSUS TIPS Principal Investigator & Institution: Henderson, John M,.; Chairman; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-AUG-2003 Summary: (Provided by the applicant) This multicenter prospective randomized clinical trial compares the surgical distal splenorenal shunt (DSRS) with the radiologic transjugular intrahepatic portal systemic shunt (TIPS) for variceal bleeding in good risk patients. The hypothesis to be tested is that TIPS will have a significantly higher rebleeding rate and encephalopathy incidence than DSRS. This study is entering its fifth year, and this renewal application will provide for a further 3 years of follow-up. The specific aims are to enter 140 patients- 114 have been entered by 10/2000- with a minimum 2 years and median 5 years follow-up. The study population are patients with Child's Class A or B cirrhosis who have failed endoscopic and pharmacologic therapy for their variceal bleeding. Uncontrolled studies show a variceal rebleeding rate of 20% after TIPS compared to 5% after DSRS, and encephalopathy incidence of 30% after TIPS compared to 14% after DSRS. This trial is planned with sufficient power to detect a 15% difference in defined endpoints. The health related importance of this study is in defining the role of these two decompression therapies in terms of variceal bleeding control, change in liver function (encephalopathy, ascites, liver failure, need for transplant), mortality, quality of life and costs. Data collection and analysis of these endpoints constitute the goal of this application. This renewal application plans to extend this trial to allow the five Clinical Centers to complete patient recruitment and provide longer term follow-up and data collection on all randomized patients. The Data Coordinating Center is responsible for data verification, management and analysis. The extension of this trial, will provide the most comprehensive and longest follow-up for these two shunt procedures for control of variceal bleeding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTICENTERED RANDOMIZED TRAIL OF HIGH-DOSE URSO IN PSC Principal Investigator & Institution: Lindor, Keith D.; Professor and Director; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006
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Summary: (provided by applicant): Primary sclerosing cholangitis (PSC) is a progressive chronic cholestatic liver disease of unknown etiology that is commonly associated with chronic colitis. PSC, a common liver disease among adults, usually leads to advanced liver disease and liver failure, and as such, is an important indication for liver transplantation. Unfortunately, no effective medical therapy currently exists for PSC. The group of investigators has a longstanding track record of clinical trials in chronic cholestatic liver disease, particularly in primary sclerosing cholangitis. Recently we have generated promising results from a pilot study using high doses of ursodeoxycholic acid in the treatment of PSC. Lower doses of ursodeoxycholic acid in patients with PSC led to biochemical improvement but did not affect other clinically important endpoints in a previous study. Our pilot data is supported by data from another group showing in a small, randomized trial that high dose ursodeoxycholic acid led to biochemical, histologic, and cholangiographic improvement compared to placebo at two years. In this submission, we propose a large-scale multi-center placebo-controlled randomized trial with a minimum follow-up of four years for 150 patients with primary sclerosing cholangitis. Primary endpoints of the study will include histologic progression to cirrhosis, development of esophageal or gastric varices, need for liver transplantation, and survival. Secondary endpoints will include measurements of the effects of urosodeoxycholic acid (28-30 mg/kd/d) on liver biochemistries, histologic stage, cholangiographic features, Mayo risk score, and quality of life, using validated questionnaires. This study will be the largest ever conducted in PSC and the follow-up will be the most extensive. This will provide an invaluable resource for studying the natural history of this disease and as part of this study we will also collect serum, cells for extraction of DNA, bile, and tissue from the liver and colon as a resource for future studies. The multi-centered nature of this trial will allow recruitment of patients into this study from a diverse patient population, representative of the gender and racial distribution of this disease. Chances of successful completion of this study are enhanced by the large PSC patient population that the participating centers currently manage, recognition of these sites as referral centers for new patients with PSC, as well as a longstanding track record in clinical trials in cholestatic liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NANOLITER DEVICE FOR HEPATITIS C DETECTION Principal Investigator & Institution: Brahmasandra, Sundaresh; Handylab, Inc. 3310 Plymouth Rd, Ste 400 Ann Arbor, Mi 48105 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 30-JUN-2003 Summary: (Provided by applicant): HCV is a widely prevalent RNA virus with 200 million individuals worldwide, and 4 million Americans are chronically infected with HCV. Patients with chronic HCV infection are at risk of developing cirrhosis, liver failure and hepatocellular carcinoma. Rapid diagnosis of HCV can lead to early treatment and prevention of transmission. While enzyme immunoassays for the detection of hepatitis C antibody are inexpensive and reliable in the screening of HCV infection, they do not differentiate between recovered and chronic infection, and are of no value in monitoring response to treatment. Qualitative and quantitative reverse transcription-PCR (RT-PCR) assays are available for the diagnosis and monitoring of HCV infected patients but these tests have significant drawbacks of high cost, long analysis times, limited range of linearity, and requirement of skilled labor. We propose to develop a portable, self-contained, microfabricated device for the diagnosis of infectious diseases using real-time polymerase chain reaction (PCR) to detect and quantify the levels of HCV viral load. Such a device could significantly reduce costs and
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dramatically improve the quality of care of HCV infected patients. Our ultimate goal is to develop a self-contained, inexpensive, microfabricated device that can detect the presence as well as concentration of one or more infectious agents in near-patient setting. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUTROPHIL-INDUCED LIVER INJURY TOXICITY Principal Investigator & Institution: Jaeschke, Hartmut W.; Professor; Pharmacology and Toxicology; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-OCT-2002 Summary: Neutrophils can cause impaired liver function, parenchymal injury and even liver failure during a number of important clinical situations including hepatic ischemia-reperfusion, hemorrhagic shock and resuscitation, endotoxemia and sepsis, remote traumas, well as alcoholic hepatitis. Although neutrophils can accumulate rapidly in hepatic sinusoids and post-sinusoidal venules, migration into the extravascular space and direct attack on parenchymal cells leads to the most serious and irreversible injury. Our previous work defined the unique behavior of neutrophils in the liver vasculature and the conditions necessary for injury to occur. Although we clearly established the importance of cytokines, adhesion molecules and neutrophil activation in vivo, our data strongly suggest that a chemotactic signal must be generated to trigger neutrophil transmigration. Preliminary data showed a protective effect of an antiserum against MIP-2 after galactosamine/endotoxin treatment. Therefore, we hypothesize that members of the CXC chemokine family, KC and MIP-2 are involved in neutrophil activation and sequestration in the liver vasculature. In addition, CXC chemokines are responsible for extravasation into the parenchyma and are a key signal for the attack on individual hepatocytes. Moreover, parenchymal cell apoptosis can be a proinflammatory event by modulating the transcriptional regulation of CXC chemokines. To test these hypotheses, we will address the following specific aims: 1) Define the relevance of CXC chemokines in comparison to other inflammatory mediators in the activation and recruitment of neutrophils into the liver vasculature during endotoxemia in vivo. 2) Determine if CXC chemokines are a relevant signal for transmigration of neutrophils in the liver during endotoxemia in vivo. 3) Determine if CXC chemokine formation and neutrophil transmigration can be modulated by apoptotic cell death in hepatocytes during endotoxemia or Fas receptor ligation in vitro and in vivo. 4) Determine CXC chemokine formation in hepatocytes and/or neutrophils and their pathophysiological importance in the adherence-dependent killing of hepatocytes by neutrophils in vitro. We will perform these studies in well-defined models of inflammatory liver injury in vivo and in vitro using C3HebIFeJ mice. In addition, a number of gene knock-out mice with deletions of specific receptors, e.g. CXC chemokine receptor 2, TNF receptor 1, IL-i receptor 1 and antioxidant enzymes, e.g. glutathione peroxidase, will be used. This investigation will provide important new insights into the molecular mechanisms of neutrophil- induced liver injury and will help to identify potentially selective therapeutic intervention strategies that can be used to prevent neutrophil cytotoxicity without affecting vital host-defense functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NRSA HEPATOLOGY TRAINING GRANT Principal Investigator & Institution: Peters, Marion G.; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747
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Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): Liver disease is among the ten most important causes of death in the United States. However, over the last 10-15 years, there has been a remarkable expansion of basic knowledge in liver biology. This knowledge has led to new modalities for managing the various forms of acute and chronic liver disease. Treatments of viral hepatitis and liver transplantation have captured the headlines, but considerable progress has occurred also in therapy of portal hypertension, gene transfer, and cell transplantation for genetic liver disease, bioartificial liver support for acute liver failure, pathogenesis and therapy of cholestatic diseases, antifibrotic therapy and many others. The extraordinary progress has created a demand for well-trained hepatologists, in particular those who both contribute to current advances in basic knowledge and take disease management to the next level. While progress has been impressive, hepatitis C, hepatocellular carcinoma, and obesity-related liver disease (nonalcoholic steatohepatitis, or NASH) are looming epidemics, for which liver transplantation will not be a realistic solution for all, given the limitation of organ supply. Therefore, we see the training of research hepatologists as a national priority. The Division of Gastroenterology at UCSF has a 30 year history of preeminence in the research and treatment of liver diseases, with an NIH-funded Liver Center since 1975 and, since 1988, a Liver Transplant Program in partnership with the Department of Surgery. Through the Liver Center and joint mentorship of trainees, the Division is closely allied also with the basic sciences at UCSF and the Immunology Program in particular. This application is for funds for a two-year training experience in clinical or basic research, for two individuals annually, in Advanced Hepatology. The program faculty represents the Departments of Immunology/ Microbiology and Pathology as well as Medicine and Surgery. Fellows who select clinical research will receive formal training in clinical/outcomes methodology, with an option to earn an MS or MPH degree. Those in basic or translational laboratory research have a broad array of possibilities with formal courses and a richly supportive environment. Each trainee will have an individual oversight committee to review progress and provide feedback. Graduates of the program will have a productive research program and be fully prepared for a junior faculty position and ideally trained to successfully apply for NIH funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: P27KIP1 IN HEPATOCYTE PROLIFERATION Principal Investigator & Institution: Zhu, Liang; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Studies in the field of cell cycle regulation have identified many important cell cycle regulators and provided a wealth of knowledge about how cell proliferation is controlled in various settings. The kinase inhibitor p27Kipl inhibits the kinase activity of various cyclin-dependent kinases to restrain cell proliferation. Targeted inactivation of p27 in the mouse results in proportionally enlarged animals with multi-organomegaly. The livers of these animals contain about 25% more apparently normal hepatocytes but do not have increased incidence of hepatocellular carcinoma. We reasoned that this property of p27 in hepatocytes may be used to benefit hepatocyte-based therapies. We have recently reported that hepatocytes isolated from p27 knockout mice demonstrated improved proliferation ability in a mouse liver failure transplantation model, providing initial experimental support for our hypothesis that manipulation of p27 could be a useful approach to improving the efficiency of hepatocyte transplantation. The objective of this application is to gain a
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Liver Failure
better understanding of p27 in hepatocytes with next-level p27 targeting strategies, which will then enable us to better evaluate the potentials of targeting p27 in human hepatocyte transplantation. In Specific Aim 1, we will generate hepatocyte-specific, inducible p23 knockout mice to study the role of p23 in hepatocytes at various stages in the liver. We will then use hepatocytes isolated from these mice to determine the functional role and mechanisms of p27 in hepatocyte proliferation in vitro (Specific Aim 2) and after transplantation (Specific Aim 3). In Specific Aim 4, we will determine the role of p27 in hepatocellular carcinogenesis in two mouse liver tumor models that involve extensive hepatocyte proliferation prior to oncogenic transformation. Successful completion of these studies will provide a solid knowledge of p27 in hepatocytes. This knowledge will form the foundation by which hepatocyte proliferation is controlled, which is essential for finding rationale ways to manipulate hepatocyte proliferation to benefit the treatment of liver diseases and liver gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PIVOTAL PHASE II & III STUDY OF HEPATASSIST LIVER ASSIST SYSTEM (LAS) Principal Investigator & Institution: Demetriou, Achilles; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREDICTING LIVER DISEASE IN HIV-HCV-INFECTED WOMEN Principal Investigator & Institution: Taylor, Jill; Wadsworth Center Empire State Plaza Albany, Ny 12237 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The purpose of this retrospective pilot study is to identify adaptive mutations that are selected in nonstructural coding regions of the hepatitis C virus (HCV) genome. The dominant virus population that was present in women co-infected with Human Immunodeficiency virus (HIV) and HCV, when clinical signs of progressive liver disease were apparent, will be analyzed. The long-term goal is to understand the viral genomic characteristics of HCV that result in enhanced viral replication, and lead, in conjunction with host immunity and environmental factors, to liver damage. The central hypothesis is that efficient replication of specific HCV variants with enhanced growth properties contributes to liver damage. It is postulated that the enhancement of viral replication is due to the selection of adaptive mutations in the nonstructural coding regions of the genome. This viral population can then become dominant over time in a hepatic environment in which control of viral replication has been weakened by HIV-induced immunosuppression, alcohol and substance abuse. To test this hypothesis we will sequence the NS3/NS4A and NS5B nonstructural coding regions of the HCV genome in virus from HIV-HCV co-infected women with and without clinical signs of progressive liver disease. The rationale for the proposed research is that once specific mutations are identified as markers of advanced disease, a prognostic assay can be developed to identify patients at higher risk of progression. The study population is 100 HlV-HCV co-infected women, with the additional risk factors of alcohol and substance abuse, enrolled in the Women's Interagency HIV Study (WIHS) at SUNY Downstate in Brooklyn, NY. The experienced investigators collaborating on this proposal represent the cross-disciplinary fields of molecular virology, HIV-HCV
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primary care and clinical research, and biostatistics. The WIHS cohort at SUNY Downstate has been selected, not only because of the availability of robust demographic and clinical information and stored plasma samples collected since 1994, but also because of the potential for expansion to include the entire WIHS cohort of >2,000 women. HIV-HCV co-infected individuals have been specifically chosen because of the mounting evidence that HIV infection exacerbates HCV disease. Liver failure has become a leading cause of death in the HIV-HCV co-infected population, emphasizing the urgent public health need for earlier treatment intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREDICTING OUTCOME--ALCOHOLIC LIVER TRANSPLANT PATIENTS Principal Investigator & Institution: Dimartini, Andrea F.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: APPLICANT'S ABSTRACT: Alcoholic Cirrhosis is the most common reason for liver failure and the largest diagnostic category receiving liver transplantation. However, factors that shape policy, treatment choices, candidate selection, and public options are strongest against this group. Without guidance from rigorous research data, the future for alcohol cirrhotics pursuing transplantation is uncertain. To date, no studies of outcome in alcoholic cirrhotics have used alcohol research measures or models, as proposed herein. In the transplant literature there is a lack of consistency in relapse definitions, timing or methods of follow-up, or use of post-transplant factors to predict alcohol use. This proposed research will expand the primary aim of alcohol research which is to identify and explain the factors that shape alcohol use and its consequences in various populations. To investigate outcome in alcoholic cirrhotics undergoing liver transplantation, expertise in psychiatry, medicine, transplantation, and alcoholism is needed. The applicant, an M.D. board certified in psychiatry, has the basic requisite skills to embark on this line of research. Through five years of clinical work evaluating, treating, and following alcoholic cirrhotic patients pursuing transplantation the applicant has developed a high degree of clinical acumen as well as the necessary connections to one of the largest liver transplant teams in the U.S. This Mentored Clinical Scientist Development Award will allow the applicant the opportunity to consolidate clinical skills in conjunction with a structured educational program and mentored research. During the award period, the candidate will conduct a prospective longitudinal study of alcohol use following liver transplantation, while investigating pre-transplant and post-transplant factors hypothesized to influence return to drinking. This research experience will be complemented by career development activities supervised by pioneering researchers in addictions, transplantation, and psychiatric research. The proposed plan is designed to develop the candidate's expertise in: 1) longitudinal study design and analysis; 2) alcohol relapse identification and monitoring; 3) conceptual and analytic modeling of relapse factors; and 4) post-transplant alcohol use outcome, and will give her the necessary skills to become an independent academic researcher in addictions and transplantation research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTING DEPRESSION IN MMT PATIENTS ON INTERFERON Principal Investigator & Institution: Ramsey, Susan E.; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903
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Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2006 Summary: (provided by applicant): To date, the use of psychosocial interventions to prevent the major depressive episodes that are commonly precipitated by antiviral treatment for the hepatitis C virus (HCV) has been unexplored. However, cognitivebehavioral treatments for depression (CBT-D) have demonstrated efficacy in a number of different populations, including substance abusers and individuals with medical problems, and have been found to be efficacious in the prevention of depression. The long-term objective of this research program is to improve depression prevention options for methadone maintenance treatment (MMT) patients undergoing interferon (IFN) treatment for hepatitis C by developing and establishing the efficacy of a CBT-D intervention tailored to this population. Furthermore, we seek to advance knowledge of the relationship between depressive symptoms and IFN treatment adherence and illicit drug use relapse. In the present application, we propose to develop a CBT-D intervention tailored to meet the needs of MMT patients undergoing antiviral treatment for hepatitis C. In the first phase of this project (Year 1), we will develop and pilot the intervention with 20 patients. In the second phase of the project (Years 2 and 3), we will conduct a preliminary, randomized trial with 60 MMT patients to examine the efficacy of the CBT-D intervention relative to the relaxation training (RT) control condition that equates for therapist contact time. We expect that, relative to the RT condition, participants randomized to the CBT-D condition will have decreased likelihood of depression-related antiviral treatment failure, will report lower levels of depressive symptoms, will complete more IFN injections, will have lower HCV RNA levels, and will have fewer illicit drug use days. If the efficacy of this intervention can be established in this trial and in subsequent clinical trials, MMT patients who elect to undergo antiviral therapy will have a valuable adjunct or alternative to the use of antidepressants to prevent depression. If found to be efficacious, this intervention will maximize the receipt of IFN treatment by MMT patients, thereby aiding in the prevention of liver failure, hepatocellular carcinoma, and liver-related death among those with HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF CELL LINEAGE SPECIFICITY IN THE LIVER Principal Investigator & Institution: Lee, Sum P.; Professor and Chief; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 28-FEB-2006 Summary: (provided by applicant): Classical stochastic view of cell growth and differentiation insists on a specific progenitor cell origin, a process of growth resulting in a mature (terminally differentiated) cell which cannot further divide. In the liver, a pluripotential stem (oval) cell gives rise to both hepatocytes and biliary ductal cells. A bone marrow derived progenitor cell also contributes to the growth and differentiation of liver and biliary ductal cells. Recent emphasis has focused on the plasticity of stem cells. The concept of 'plasticity' of the well differentiated cell has been largely ignored. This proposal examines the provocative hypothesis that it is possible to have transdifferentiation between the mature cells of the hepatocyte and biliary epithelial cell lineages. Mature hepatocytes and biliary duct epithelia divide actively in vivo and in vitro. Culture conditions in vitro (growth factors, cytokines, extracellular matrix) can induce phenotypic transdifferentiation of hepatocytes into biliary cells and vice versa. Experiments are designed to (1) further characterize a biliary cell line which we have established from the MT-lacZ mouse, with a transgene encoding Beta-galactosidase (Xgal) driven by an albumin promoter and hence only hepatocytes will stain blue. (2)
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induce transdifferentiation of biliary cells into hepatocytes in vitro, Cells will be studied with lineage-specific and maturation-dependant markers, albumin secretion, and X-gal positivity. The potential role of Notch gene in regulating cell lineage decision will be studied. Notch pathway gene expression during cell growth and differentiation will be determined using semi-quantitative RT-PCR. In addition, the functional role in cell lineage commitment and differentiation will be studied by inducing Notch signalling using exogenous Notch ligands (Jagged 1, Delta 1). (3) study the in vivo propagation of transdifferentiated cells by implanting them into the omental compartment of congenic mice, and (4) to use transdifferentiated cells of biliary origin in cell transplantation to repopulate and rescue the dying livers of Albu-PA mice (carrying a cytotoxic transgene resulting in liver failure). The results of these experiments will yield new, important information on cell lineage specificity, regulation of cell commitment and cell fate, and the effect of instructive transdifferentiation. It potentially can open up a new field of using mature cells of the same embryonic origin to mediate gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF EICOSANOIDS IN MODULATING ENDOTOXIN INDUCED LIVE Principal Investigator & Institution: Brigham, Kenneth L.; Professor of Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 30-NOV-2006 Summary: In the clinical setting of sepsis related ARDS, the presence of liver failure markedly increases mortality and studies of endotoxin induced lung injury in animals implicate effects on the liver as important for the full expression of the injury. The sequence of biochemical events that dictates the physiologic response to endotoxin may be activation of critical transcription factors, especially nuclear factor kappa B (NFkappaB) and CCAAT enhancer binding protein beta (C/EBPbeta, a.k.a. NF-IL6) in both the lungs and the liver, leading to generation of pro-inflammatory cytokines. Our preliminary data as well as data of others implicate eicosanoids as modulators of these endotoxin effects and induction of the cyclooxygenase (COX-the proximal enzyme in prostanoid synthesis) also involves NFkappaB and C/EBPbeta activation. To elucidate relationships among the physiologic, biochemical, molecular and pathophysiologic events related to liver-lung interactions in the endotoxin response we propose a series of studies in an in situ perfused swine model in which the lungs can be perfused with or without the liver in the perfusion circuit. We will: 1) determine effects of endotoxemia on pulmonary vascular resistance, lung vascular permeability, lung water content, tissue, perfusate and bronchoalveolar lavage fluid (BALF) concentrations of eicosanoids and cytokines, BALF total and differential cell counts, expression of TNFalpha, COX-1, COX- 2 and 5-lipoxygenase genes, activation of nuclear factor kappa B (NFkappaB) and C/EBPbeta in the lungs (and liver) with and without inclusion of the liver in the perfusion circuit; 2) manipulate concentrations of prostanoids in lung or liver by local controlled infusion of PGE2 into either organ, targeted delivery of a COX inhibitor to liver or lungs or transfecting the organ(s) with a construct expressing the COX gene and determine effects of these interactions on generation of eicosanoids and on endotoxin responses; 3) increase p20, the inhibitor isoform of C/EBPbeta, in the liver or the lungs by partial hepatic resection, delivery of a p20 membrane translocation signal fusion protein or transfection of the liver or lungs with a p20 gene and determine effects of these interventions on the endotoxin response; 4) inhibit activation of NFkappaB in liver or lungs by transfection of either organ with a gene encoding a transdominant inhibitor of NFkappaB activation or administration of a cell-permeable NFkappaB inhibitory
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fusion protein and determine effects on the endotoxin response. These studies will link pathophysiology to pathogenesis of the endotoxin response, providing a basis for identifying new potentially therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF STELLATE CELLS IN LIVER FAILURE Principal Investigator & Institution: Gandhi, Chandrashekhar R.; Research Assistant Professor of Surgery; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 25-SEP-1998; Project End 31-AUG-2007 Summary: (provided by applicant): Acute liver failure is a devastating clinical condition with a high mortality rate. This affects patients with and without prior liver disease. Inability of hepatocytes to regenerate and their progressive death leads to acute liver failure. The mechanisms of hepatocyte depletion in acute liver failure are inadequately understood, precluding effective pharmacological therapy. However, endotoxemia is always associated with acute liver failure and is a major contributor of catastrophic failure. In the United States alone more than 20,000 people die of septic shock and evidence indicates that hepatic stellate cells inevitably play a major role in response to endotoxemia. The normally quiescent stellate cells regulate liver blood flow by contractility and maintain its architecture by producing components of extracellular matrix. During chronic liver injury, stellate cells transform into proliferating, highly contractile and fibrogenic myofibroblast cells. Endotoxin causes upregulation of the endothelin system in stellate cells and the consequent profound hepatic vasoconstriction contributes to endotoxin-induced liver injury. Moreover, endotoxin-conditioned media of quiescent and activated stellate cells strongly inhibit DNA synthesis in hepatocytes. Endotoxin increases the expression of nitric oxide, IL-1-beta, IL-6, but not of TGF-beta or TNF-alpha in both phenotypes. However, none of these potent mediators is responsible for the inhibition of hepatocyte DNA synthesis. Also, stellate cells in the presence of endotoxin and reactive oxygen species release factors which kill hepatocytes. Reactive oxygen species are generated by the resident macrophages (Kupffer cells) in response to endotoxin. These observations strongly suggest the synthesis of one or more as yet unidentified mediators which promote liver failure. The specific aims of this proposal are: 1) to determine the cellular mechanisms by which stellate cells respond to endotoxin, 2) to determine the mechanisms by which stellate cells plus endotoxin- or stellate cells plus reactive oxygen species-conditioned media cause injury to hepatocytes, 3) to determine the effects and mechanisms of endotoxin treatment of normal and cirrhotic rats on stellate cell-mediated hepatocyte injury, and 4) to identify and characterize the mediators of hepatocyte injury produced by stellate cells. The outcome of this investigation will provide profound insights into the central regulatory role of stellate cells in liver pathophysiology. Importantly, identification of the stellate cell-derived mediators will provide a rational basis for the therapy of life-threatening liver failure and other liver disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ROLE OF TISSUE MICRO ARCHITECTURE ON HEPATOCYTE FUNCTION Principal Investigator & Institution: Bhatia, Sangeeta N.; Associate Professor; Bioengineering; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934
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Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 30-JUN-2004 Summary: Our overall goal is to develop highly functional hepatocellular tissue constructs that can be used in the treatment of liver failure. While there has been reasonable progress towards development of cell-based therapies for liver disease, the key determinants of high levels of liver- specific function in isolated hepatocytes have remained elusive. We and others have shown that co-cultivation of hepatocytes with non- parenchymal cells increases hepatocellular function in vitro; however, the fundamental modulators of hepatocellular function have yet to be clearly elucidated. The limitations in our understanding of relevant hepatocellular cues is, in part, due to the spatial complexity of multicellular constructs. We have shown previously that micropatterning (spatial localization of cells on solid substrates in patterns) can be utilized to control and study key cell-cell interactions. It is our hypothesis that the same cellular constituents in different spatial configurations will produce variations in the function of the resultant tissue. In this proposal, therefore, we aim to define the relationship between tissue architecture and tissue function in co-cultures of hepatocytes and non-parenchymal cells. A clear picture of the interplay between homotypic (hepatocyte/hepatocyte) interaction, heterotypic (hepatocyte/nonparenchymal cell) signaling, and cell-matrix interactions will be fundamental to the future design and implementation of hepatocyte-based tissue engineered medical products. Towards this end, our specific aims are: l). To determine the role of homotypic (hepatocyte/hepatocyte) interactions on hepatocellular function. Homotypic interactions will be varied (from single hepatocytes to multicellular islands), and cultures probed for markers of liver-specific function. The role of ECM cues and gap junctions- normally found at the homotypic interface- will also be examined in this context. 2). To investigate the role of heterotypic (hepatocyte/non-parenchymal cell) interaction on hepatocellular function. Co-cultures of rat hepatocytes and 3T3 fibroblasts will be micropatterned such that the spatial arrangement of both cell types is specified. We have previously shown that spatial configuration may influence hepatocyte function through either: amount of heterotypic interaction or shape of hepatocellular islands. These key parameters of tissue micro-architecture will be varied and co-cultures probed for markers of liver-specific function to isolate the determinants of tissue function. The role of ECM cues and heterotypic gap junctions-putative mediators of the co-culture 'effect' will be examined. 3).To optimize functionality of tissue constructs for tissue engineering applications. We will investigate the functional consequences of reduction in non-parenchymal number as well increased heterotypic interaction through use of 3dimensional, grooved, micropatterned substrates. These studies will enable the formation of a fundamental framework that will guide the design and implementation of current and future hepatocyte-based medical therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCF IN LIVER REPAIR AFTER HEPATECTOMY OR TOXIC INJURY Principal Investigator & Institution: Colletti, Lisa M.; Associate Professor; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant)The failing liver is the only vital organ for which we have no means of pharmacologic or mechanical support. The liver is also unique in that it can regenerate a normal functional cellular mass in response to many injuries, as opposed to most organs which repair themselves with non-functional scar. Liver failure is an important clinical problem that occurs after a variety of toxic, traumatic, and
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infectious insults. Liver failure also occasionally follows major hepatic resections for tumor. More importantly, hepatic resection is often precluded when a curative resection will leave an inadequate amount of functioning hepatic tissue, ultimately resulting in the death of the patient. Accidental and purposeful acetaminophen overdose accounts for 20 percent of acute liver failure cases in the U.S. Acetaminophen poisoning causes direct hepatocyte damage and patient survival relies heavily upon the liver's ability to recover from the damage and regenerate. Acetaminophen-induced liver injury is well characterized, however, the mechanisms of liver protection, repair, and regeneration have not been fully examined. This proposal examines a specific cytokine, stem cell factor (SCF), in hepatocyte protection and regeneration during acetaminophen-induced liver toxicity, as well as following 70 percent hepatectomy. SCF is well-known as an important leukocyte hematopoietic factor, involved in the proliferation and maturation of multiple leukocyte subsets, especially mast cells. More recently, it has been shown to be an important factor in the development of normal structural cells, such as hepatocytes. We will utilize two murine models, acetaminophen poisoning and 70 percent hepatectomy, to investigate SCF's effects following liver injury. We hypothesize that SCF functions via two mechanisms, having anti-apoptotic protective effects, as well as enhancing the hepatocyte regenerative response. To test this postulate, we will focus on mechanisms of SCF-associated liver repair utilizing the following specific aims: 1) To examine the expression, production, and cellular source of hepatic SCF following 70 percent hepatectomy or acetaminophen-induced injury, 2) To examine the regulation of transmembrane versus soluble SCF and its receptor, c-kit, in the setting of toxic or traumatic hepatic injury, 3) To investigate SCF's effects and mechanism(s) of action on hepatocyte apoptosis and proliferation after toxic or traumatic hepatic injury, and 4) To investigate the interactions of SCF and IL-6 in the liver's recovery from toxic or traumatic injury. These studies will help to elucidate novel mechanisms in SCFmediated hepatocyte protection and regeneration in a clinically relevant liver resection and toxicity model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SECRETORY LINEAGES DURING INTESTINAL ADAPTATION Principal Investigator & Institution: Helmrath, Michael A.; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): As a pediatric surgeon, I have an intense interest in the management of intestinal failure in infants. The most common etiology of "shortgut" in infants is from necrotizing enterocolitis, but may also arise from volvulus, atresias, gastroschesis, and Hirschsprung's disease. Following massive intestinal loss, the remaining intestine attempts to adapt by enhancing proliferation of intestinal stem cells and their progeny resulting in marked increases in the remaining mucosal surface area aiding absorption and digestion. Failure of this process to adequately compensate require many children to depend on parenteral nutrition (TPN) to sustain adequate nutrition subjecting them to the many inherent risks of TPN, including cholestasis and liver failure. Developing new therapies to augment the adaptive response will require an understanding of the mechanisms that stimulate intestinal stem cells and their progeny following massive intestinal loss. My ongoing studies in the laboratory of Susan Henning Ph.D. are evaluating the role of secretory lineages during intestinal adapation, and have demonstrated an early increased production of intestinal secretory lineages occurs following resection. I hypothesize that the early increased production of intestinal secretory lineages following massive intestinal loss is essential to amplify the
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early signals initiating intestinal adaptation. This grant proposes the use of a specific progenitor assay somatic mutation (SPASM) sytem to identify dynamic changes within intestinal progenitor compartments that occur following a 50% intestinal resection in mice. The early role of secretory lineages initiating intestinal adaptation will further be evaluated by performing similar intestinal resections on mice harboring a mosiac inactivation of all secretory lineages in the terminal ileum and on normal mice following administration of growth factors that previously have been shown to stimulate only secretory or columnar lineages. The development of flow cytometry techniques to separate and quantitate epithelial lineages will provide an efficient tool to further assess the molecular mechanisms initiating the early adaptive response. The excellent environment provided by Dr. Henning's laboratory and the support of this application will provide a solid foundation for the development of an independent translational reseach career exploring the mechanisms of intestinal adaptation and treatment of intestinal failure in children Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF THE NATURAL HISTORY OF HEPATITIS C IN LIVER Principal Investigator & Institution: Carithers, Robert L.; Director of Hepatology Section; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Chronic hepatitis C virus infection has emerged as the most important form of viral hepatitis in the United States. Although the disease often remains indolent for many years, approximately 20 percent of patients with chronic hepatitis C progress to cirrhosis within 20 years. As a consequence, liver failure from chronic hepatitis C has become the leading indication for liver transplantation both in the United States and Europe. Despite remarkable progress in our understanding of many aspects of this disease, the mechanism of hepatocellular injury in patients with chronic hepatitis C is not well understood. Unfortunately, neither efficient cell culture systems nor animal models are available to study the pathogenesis of the liver disease. Given these limitations, we have systematically examined the evolution of liver injury in patients with recurrent hepatitis C after liver transplantation. By correlating the degree of injury to the transplanted organ with detailed analyses of viral replication we hope to provide insights into the pathogenesis of liver cell injury in these chronically infected patients. This proposal is designed to examine the hypothesis that differing patterns of mutation in the genomic sequence of HCV RNA have a profound influence on the severity of liver injury in patients with recurrent hepatitis C after liver transplantation. Our Specific Aim 1 is to prospectively determine the relationship between evolution of HCV quasispecies and hepatocellular injury in patients with recurrent hepatitis C. In Specific Aim 2 we plan to intensively investigate the clonal evolution of quasispecies and to determine the tissue origin of these viral strains both in patients with severe recurrent hepatitis C and in those with mild hepatocellular injury after liver transplantation. We plan to test the hypothesis that the primary site of quasispecies replication is critical to the development of hepatocellular injury. We propose that emergence of nonpathogenic strains of virus after liver transplantation result from continuous extrahepatic replication of HCV, whereas pathogenic strains of HCV originate from intrahepatic replication of the virus. In Specific Aim 3 we plan to assess in impact of HCV genotype, circulating levels of virus, and evolution of HCV quasispecies on the long term evolution of histologic injury in the transplanted liver. By carefully correlating the evolution of the virus with the degree of hepatocellular injury experienced by patients who develop recurrent hepatitis C after liver transplantation, we hope to provide insights into to the pathogenesis of this
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important liver disease. From these detailed analyses we also hope to isolate pathogenic strains of virus which can later be tested in cell culture systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDY OF T CELL CHARACTERISTICS AND ADHESION MOLECULES Principal Investigator & Institution: Bergasa, Nora V.; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Primary biliary cirrhosis (PBC) is chronic liver disease of unknown etiology. Histologically, PBC is characterized by a progressive immunologically mediated inflammation known as chronic nonsuppurative destructive cholangitis (CNSDC) that leads to bile duct destruction, ductopenia and biliary cirrhosis. At present there is no cure for PBC. The most common symptoms associated with PBC are fatigue and pruritus. More than 90% of patients with PBC are women. The average age of diagnosis is about 50 years. Asymptomatic patients have a four-fold increase in mortality when compared to the U.S.A. population matched for age and the median survival from the onset of symptoms is 7.5 to 9 years. PBC is considered a model autoimmune disease; it is associated with hypergammaglobulinemia, autoantibodies, defects of immune regulation, and an increased incidence of other autoimmune conditions (thyroiditis, Sjogren's syndrome, scleroderma). The liver injury is characterized by a rich inflammatory infiltrate composed of CD4+ and CD8+ cells, cytokines, adhesion molecules and other immunologic mediators. The consequence of CNSDC is biliary cirrhosis and liver failure. The only treatment approved to treat PBC is ursodeoxycholic acid (UDCA), which appears to delay the time to liver transplantation but does not cure for the disease. Thus, the need for the provision of effective and safe treatments for PBC is clear. Patients with PBC may benefit from treatment with an appropriate immunosuppressive drug. Mycophenolate mofetil meets the criteria of a superior immunosuppressive agent. In this proposal we are going to explore immune mediators of PBC including T cells and adhesion molecules in patients with PBC and the effect of treatment with MMF in combination with UDCA on these factors in patients who are participants in a clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SURGERY FOR NEC IN HUMAN INFANTS-- A RANDOMIZED TRIAL Principal Investigator & Institution: Moss, R L.; Surgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Necrotizing enterocolitis (NEC) is a severe inflammatory disease of the intestine that occurs in premature and low birth weight infants. In its most severe form, NEC results in perforation of the bowel mandating surgical intervention. It is the most common surgical disease of the newborn and results in over 2500 deaths per year in this country. The mortality rate for perforated NEC remains largely unchanged over the past 10 years. Traditional surgical therapy includes laparotomy, bowel resection, and creation of intestinal stomas (LAP). Simple primary peritoneal drainage (PPD) of the abdominal cavity is a novel, minimally invasive alternative. Experience with both of these treatments is broad but their outcomes have never been compared in a meaningful fashion. Our primary aim is to perform a clinical trial to determine whether peritoneal
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drainage improves survival over laparotomy and bowel resection in babies less than 1500 grams. Our secondary aims are to determine whether PPD affects gastrointestinal morbidity, length of hospital stay, and cost of care. The unique resources of UCSF Stanford Health Care will allow us to enroll a population of sufficient sample size yet maintain the rigid standardization of operative technique and patient care necessary for a successful surgical trial. We will enroll infants less than 1500 grams with perforated NEC and randomize their operative treatment to PPD or LAP. Postoperative care will follow an adopted clinical pathway. Statistical analysis will use survival as the primary outcome. Inference will be based on a "cure rate" model" and a log rank statistic. The design is sequential allowing for an "early" look at the data after 37 patients. If evidence is overwhelmingly in favor of one group we will stop. Otherwise we will continue until 88 patients are accrued. Secondary variables will be analyzed by Cox regression with adaptively chosen covariates from a stated list involving sample reuse methods to make inferences regarding parameters. As with many problems in Pediatric Surgery, single institutions do not have sufficient experience with NEC to complete meaningful studies. We believe that we have the necessary personnel and resources in place to complete the first randomized controlled trial for neonatal surgery in the United States. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T CELL IMMUNITY & LIVER FIBROSIS IN HCV/HIV COINFECTION Principal Investigator & Institution: Morishima, Chihiro; Pediatrics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The advent of Highly Active Anti-Retroviral Therapy (HAART) has led to a significant increase in life expectancy for human immunodeficiency virus (HIV)-infected individuals, prompting attention toward conditions such as hepatitis C virus (HCV) coinfection, which may adversely affect the lifespan and quality of life of HIV-infected persons. A significant number of individuals in the United States are infected with both HCV and HIV: 60%-90% of hemophiliacs and 50%-90% of injection drug users. In addition, a growing number of reports indicate that accelerated progression of liver fibrosis and increased rates of liver failure are found in HCV/HIV coinfection compared to those infected only with HCV. This rapid progression of liver disease has been found to correlate with lower peripheral blood CD4+ T cell counts, suggesting a link between CD4+ T cells and liver fibrosis progression. The overall goal of this proposal is to better understand the pathogenesis of HCV coinfection with HIV by investigating the relationship between liver fibrosis, intrahepatic HCV replication, and the quantity and function of HCV-specific intrahepatic CD4+ T cells, including their ability to secrete cytokines that promote fibrosis. Finally, we will test the hypotheses that HCV/HIV coinfected subjects treated with HAART will demonstrate improved HCV-specific CD4+ T cell function that is not fibrogenic, and is sequestered to the liver. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE CNS AND CIRRHOSIS:PSYCHOBIOLOGICAL APPROACHES Principal Investigator & Institution: Stewart, Charmaine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-DEC-2002 Summary: (provided by applicant): Hepatic encephalopathy (HE) is one of the most common manifestations of decompensated cirrhosis. Approximately 70% of patients
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with cirrhosis also have subacute hepatic encephalopathy (SHE), as demonstrated on neuropsychological testing. The use of transjugular intrahepatic portosystemic shunts (TIPS), which acts as a side-to-side shunt, has become common to manage complications of cirrhosis. However, TIPS are associated with adverse effects, including worsening of existing HE or the precipitation of overt HE and liver failure. Liver transplantation has become the ideal management for patients who have decompensated liver disease. The principal hypothesis of this proposal is that changes of HE and SHE can be determined by neuropsychological testing and changes in cerebral blood flow (CBF). The Specific Aims are the following: (1) Determine the changes in cognitive function in patients with cirrhosis; (2) Identify changes in CBF and neurotransmitter activity, as assessed by central benzodiazepine receptor binding and serotonin transporter binding after TIPS insertion; (3) Identify changes in CBF and neurotransmitter activity, as assessed by central benzodiazepine receptor binding and serotonin transporter binding after liver transplantation; and (4) Correlate the neuropsychological changes with cognitive function and central benzodiazepine receptor binding and serotonin transporter binding. These Specific Aims will be pursued in 60 subjects: group I will be 20 cirrhotics who will undergo TIPS; group II will be 20 cirrhotic patients who are scheduled to undergo liver transplantation; and group III will be 20 age and sex matched cirrhotic controls. All groups will be studied with a battery of neuropsychological tests and stimulated CBF, using 1502 labeled water, while half of groups I and II will be tested with 11C flumazenil PET or (11C)(+)McN5652 positron emission tomography (PET), in order to determine central benzodiazepine receptor binding and serotonin transporter binding, respectively, before and one month after undergoing TIPS or liver transplantation. The control group will be studied with 11C flumazenil PET or (11C)(+)McN5652 PET at baseline and 1 month, thereafter. In aggregate, these studies will provide a platform to elucidate cognitive and biological mechanisms underlying hepatic encephalopathy with the ultimate goal of enhancing diagnosis and management. Additionally, the proposed studies will be guided by a team of mentors and sponsors and supplemented by a didactic curriculum, all to lay the foundation for eventual independent clinical investigator status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE EPIDEMIOLOGY OF HEPATITIS C INFECTION IN THAILAND Principal Investigator & Institution: Nelson, Kenrad E.; Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 20-SEP-1999; Project End 31-AUG-2004 Summary: The proposed research program will involve integrated collaborative studies of the epidemiology, biology and natural history of hepatitis C virus (HCV) infections in Northern Thailand. Infections with HCV are a worldwide health problem and are a major cause of chronic liver disease, liver cancer and cirrhosis. It is estimated that 4 million persons in the United States and 180 million persons worldwide are infected with HCV. After infection 80 percent of individuals will become chronic carriers and 20 percent of them will progress to chronic liver disease or cancer in the next 15-20 years. Epidemiologic studies in some populations have found high rates of HCV in injection drug users and lower but elevated rates from sexual and perinatal transmission. However, infections in many individuals are cryptogenic. The reasons for the persistence of HCV infection in such a high proportion of infected individuals is not clear. However, the virus is genetically quite diverse and viral variation with the emergence of new quasispecies usually occurs in chronically infected people. Furthermore the epidemiology and transmission of HCV is intertwined with HIV, so
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many persons who are infected with both viruses may be immunosuppressed. The studies we have planned will involve comprehensive investigations of the epidemiology, virology and natural history of HCV infections in various populations in Northern Thailand, most of whom are being evaluated for HIV infection. Liver cancer is one of the leading causes of cancer in Thailand and HCV prevalence in blood donors is 8-10 fold greater than in the U.S. The study populations will include injection drug users, sex workers, STD patients, military recruits, blood donors and their spouses and general community populations. Through the transfer of technology for HCV research to our collaborators, we hope to focus on understanding the biology and epidemiology of HCV and the development of more effective prevention of HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ENCEPHALOPATHY
PERMEABILITY
TRANSITION
IN
HEPATIC
Principal Investigator & Institution: Norenberg, Michael D.; Professor; Pathology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with severe liver failure. Acute HE associated with fulminant hepatic failure has an extremely poor prognosis and specific therapy is not available, short of an emergency liver transplantation. Although its pathogenesis remains poorly understood, ammonia is strongly implicated as a neurotoxin, and astrocytes appear to be the primary target of ammonia neurotoxicity. Additionally, altered bioenergetics and oxidative stress are thought to play a major role in this disorder. These facts led to a consideration of the involvement of mitochondrial permeability transition (MPT) as a factor in the pathogenesis of HE and ammonia neurotoxicity. The MPT is a Ca2+-dependent, cyclosporin A (CsA)-sensitive process due to the opening of a pore in the inner mitochondrial membrane leading to a collapse of ionic gradients and ultimately to mitochondrial dysfunction. We have recently shown that ammonia induced the MPT in cultured astrocytes. We intend to examine the role of the MPT in HE and hyperammonemia using ammonia-treated neural cell cultures and in vivo models of HE/hyperammonemia (HA). Our working hypothesis is that ammonia induces the MPT in astrocytes, culminating in mitochondrial failure and astroglial dysfunction. A corollary of this concept is that inhibition or interference in the development of the MPT in astrocytes may ameliorate CNS dysfunction in HE. The Specific Aims of this proposal are: 1) To identify the factors responsible for the ammonia-induced MPT in cultured neural cells. Our focus will be on agents implicated in the pathogenesis of HE/H that have also been shown to induce the MPT in other cells. Specifically, we will examine the role of Ca 2+, reactive oxygen species, nitric oxide, pH and glutamine. We will determine whether these factors are elevated in ammonia-treated cultures, and whether diminishing their production or blocking their actions reduces or abolishes the MPT. Additionally, we will examine possible sequential interrelationships among these factors. 2) To determine whether ammonia-induced abnormalities in astrocytes (morphological alterations, defects in neurotransmitter uptake, and cell swelling) are mediated by the MPT, we will investigate whether inhibitors of the MPT (CsA, bongkrekik acid) are capable of diminishing or blocking the deleterious effects of ammonia. 3) To investigate the involvement of mitochondrial dysfunction as a potential factor in MPT-mediated cell injury. We will determine the state of mitochondrial function after ammonia treatment, and then investigate whether improving energy metabolism will inhibit ammonia-induced cellular injury. 4) To
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clarify whether the MPT occurs in in vivo models of HE (thioacetarnide treatment) and hyperammonemia. We will also determine whether factors that inhibit the MPT in vitro (e.g., CsA, trifluoperazine) are also capable of doing so in vivo. Additionally, we will assess the ability of MPT blockers to improve the clinical, histopathologic, neurochemical abnormalities, and the extent of brain swelling observed in HE/HA. We believe that these studies will yield critical data bearing on the pathogenesis of HE, and may potentially aid in the development of novel therapeutic strategies for the treatment of this condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE PROGRESSION OF HEPATITIS C AMONG IDUS Principal Investigator & Institution: Thomas, David L.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): In the United States, injection drug use is the principal route of hepatitis C virus (HCV) transmission and most persons who inject illicit drugs (IDUs) have HCV infection. The chief medical consequence of HCV infection is liver failure, which occurs after a progressive accumulation of fibrosis, a process that currently can only be detected reliably by biopsy. By carefully evaluating (including a liver biopsy) a random sample of 210 community-based, HCV-infected IDUs, we learned that some IDUs met published treatment criteria but almost none had been treated and that passive methods of counseling and referral did not improve treatment acquisition. These findings have led us to investigate methods to improve care delivery by (1) intensive case-management of the subset of IDUs that most need treatment and (2) detection of that subset by testing minimally-invasive markers of significant liver fibrosis. In this grant, we propose using the unique resources already established to expand our understanding of liver fibrosis progression among IDUs. The first aim is to evaluate demographic and behavioral markers of fibrosis progression. By the start of this investigation, a second liver biopsy will have been done on IDUs from the original group of 210. The rate of progression of liver fibrosis will be calculated according to gender, age, alcohol use history, and HIV infection status by subtracting the fibrosis score of the first from the second biopsy and dividing by the years between. The second aim is to develop blood markers of fibrosis progression, using a repository of sera collected every six months and at the biopsy visits. The third aim is to expand our understanding of fibrosis progression by carefully comparing viral sequence evolution and adaptive immune responses for a subset of IDUs with a high fibrosis progression rate and controls with low rates of progression. Collectively, this research will expand our understanding of liver fibrosis progression, substantially improving our ability to identify HCV-infected IDUs who are at greatest risk of disease. A high likelihood of success is anticipated since the work builds on precious existing resources and will be performed by a team of investigators who have already demonstrated the necessary skills. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 “liver 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 liver failure in the PubMed Central database: •
Caspase 8 small interfering RNA prevents acute liver failure in mice. by Zender L, Hutker S, Liedtke C, Tillmann HL, Zender S, Mundt B, Waltemathe M, Gosling T, Flemming P, Malek NP, Trautwein C, Manns MP, Kuhnel F, Kubicka S.; 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164667
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Use of Fluoroquinolones in Patients with Chronic Hepatitis C Virus-Induced Liver Failure. by Kojima H, Kaita KD, Hawkins K, Uhanova J, Minuk GY.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128783
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 liver failure, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “liver failure” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for liver failure (hyperlinks lead to article summaries):
3 4
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. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A 46-year-old man with end-stage liver disease secondary to hepatitis C with diarrhea, fever, and worsening liver failure. Author(s): Chawla A. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2003 June 19; 5(2): 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603109
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A defect in the transport of long-chain fatty acids associated with acute liver failure. Author(s): Odaib AA, Shneider BL, Bennett MJ, Pober BR, Reyes-Mugica M, Friedman AL, Suchy FJ, Rinaldo P. Source: The New England Journal of Medicine. 1998 December 10; 339(24): 1752-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9845710
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Acute liver failure after administration of herbal tranquilizer kava-kava (Piper methysticum). Author(s): Brauer RB, Stangl M, Stewart JR, Pfab R, Becker K. Source: The Journal of Clinical Psychiatry. 2003 February; 64(2): 216-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633134
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Aetiology and prognostic factors in acute liver failure in India. Author(s): Khuroo MS, Kamili S. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 224-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753342
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Application of Molecular Adsorbents Recirculating System to remove NO and cytokines in severe liver failure patients with multiple organ dysfunction syndrome. Author(s): Guo LM, Liu JY, Xu DZ, Li BS, Han H, Wang LH, Zhang WY, Lu LH, Guo X, Sun FX, Zhang HY, Liu XD, Zhang JP, Yao Y, He ZP, Wang MM. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003; 23 Suppl 3: 16-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950956
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Assay to detect inhibitory substances in serum of patients with acute liver failure. Author(s): Anderson C, Thabrew MI, Hughes RD. Source: Int J Artif Organs. 1999 February; 22(2): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10212046
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Auxiliary versus orthotopic liver transplantation for acute liver failure. EURALT Study Group. European Auxiliary Liver Transplant Registry. Author(s): van Hoek B, de Boer J, Boudjema K, Williams R, Corsmit O, Terpstra OT. Source: Journal of Hepatology. 1999 April; 30(4): 699-705. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10207813
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Bacterial and fungal infection in acute liver failure. Author(s): Rolando N, Philpott-Howard J, Williams R. Source: Seminars in Liver Disease. 1996 November; 16(4): 389-402. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9027952
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Bilirubin removal by anion exchange resin in post-operative liver failure. Author(s): Miyazaki M, Sakagami K, Shiozake S, Saito S, Matsuoka J, Orita K. Source: Biomater Artif Cells Artif Organs. 1988-89; 16(5): 977-83. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3252937
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Bioartificial liver assist devices in support of patients with liver failure. Author(s): Patzer II JF, Lopez RC, Zhu Y, Wang ZF, Mazariegos GV, Fung JJ. Source: Hepatobiliary Pancreat Dis Int. 2002 February; 1(1): 18-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607616
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Bio-artificial liver support for acute liver failure: should we be using it to treat patients? Author(s): Jalan R, Williams R. Source: Transplantation. 2002 January 27; 73(2): 165-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821724
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Bleeding time in patients with cirrhosis: relation with degree of liver failure and clotting abnormalities. C.A.L.C. Group. Coagulation Abnormalities in Cirrhosis Study Group. Author(s): Violi F, Leo R, Vezza E, Basili S, Cordova C, Balsano F. Source: Journal of Hepatology. 1994 April; 20(4): 531-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8051393
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Blood lactate and outcome of paracetamol-induced acute liver failure. Author(s): Riordan SM, Williams R. Source: Lancet. 2002 August 17; 360(9332): 573; Author Reply 573-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12241691
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Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Author(s): Bernal W, Donaldson N, Wyncoll D, Wendon J. Source: Lancet. 2002 February 16; 359(9306): 558-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11867109
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Blood loss and ICG clearance as best prognostic markers of post-hepatectomy liver failure. Author(s): Nonami T, Nakao A, Kurokawa T, Inagaki H, Matsushita Y, Sakamoto J, Takagi H. Source: Hepatogastroenterology. 1999 May-June; 46(27): 1669-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430318
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Blood purification for postoperative liver failure with special reference to chronic hepatic support for those awaiting liver transplantation. Author(s): Omokawa S, Asanuma Y, Yoshida S, Kato Y, Koyama K, Sakurada T, Abe T, Miyagata S. Source: Asaio Trans. 1991 July-September; 37(3): M330-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1751173
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Blood purification of bilirubin and bile acids by plasma exchange for patients with liver failure. Author(s): Matsubara S, Okabe K, Ouchi K, Owada Y. Source: The Tohoku Journal of Experimental Medicine. 1986 September; 150(1): 83-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3775774
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Blood-brain barrier permeability to ammonia in liver failure: a critical reappraisal. Author(s): Ott P, Larsen FS. Source: Neurochemistry International. 2004 March; 44(4): 185-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602081
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Bone marrow failure in children with acute liver failure. Author(s): Tung J, Hadzic N, Layton M, Baker AJ, Dhawan A, Rela M, Heaton ND, Mieli-Vergani G. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 November; 31(5): 55761. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11144443
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Brain edema in liver failure: basic physiologic principles and management. Author(s): Larsen FS, Wendon J. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 November; 8(11): 983-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424710
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Branched-chain amino acids in chronic liver failure: good friends or hated enemies? Author(s): Rossi Fanelli F, Cangiano C. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1990 September-October; 6(5): 414-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2134568
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Can alprostadil improve liver failure in HIV-infected patients with severe acute viral hepatitis? Author(s): Reus S, Priego M, Boix V, Torrus D, Portilla J. Source: The Journal of Infection. 1998 July; 37(1): 84-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9733393
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Carbohydrate 19-9 antigen as a marker of non-malignant hepatocytic ductular transformation in patients with acute liver failure. A comparison with alphafetoprotein and carcinoembryonic antigen. Author(s): Halme L, Karkkainen P, Isoniemi H, Makisalo H, von Bogulawski K, Hockerstedt K. Source: Scandinavian Journal of Gastroenterology. 1999 April; 34(4): 426-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10365905
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Caspase 8 small interfering RNA prevents acute liver failure in mice. Author(s): Zender L, Hutker S, Liedtke C, Tillmann HL, Zender S, Mundt B, Waltemathe M, Gosling T, Flemming P, Malek NP, Trautwein C, Manns MP, Kuhnel F, Kubicka S. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 June 24; 100(13): 7797-802. Epub 2003 Jun 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810955
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Cause and prognosis in acute liver failure. Author(s): Riordan SM, Williams R. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1999 January; 5(1): 86-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9873098
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Cell-based therapy of acute liver failure: the extracorporeal bioartificial liver. Author(s): Fremond B, Joly A, Desille M, Desjardins JF, Campion JP, Clement B. Source: Cell Biology and Toxicology. 1996 December; 12(4-6): 325-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9034628
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Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure. Author(s): Schmidt LE, Svendsen LB, Sorensen VR, Hansen BA, Larsen FS. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 August; 7(8): 709-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11510016
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Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Author(s): Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Source: Hepatology (Baltimore, Md.). 1999 March; 29(3): 648-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051463
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Changes in protoporphyrin distribution dynamics during liver failure and recovery in a patient with protoporphyria and Epstein-Barr viral hepatitis. Author(s): Poh-Fitzpatrick MB, Whitlock RT, Leftkowitch JH. Source: The American Journal of Medicine. 1986 May; 80(5): 943-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3010717
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Changes in serum electrolytes during treatment of patients in liver failure with molecular adsorbent recirculating system. Author(s): Doria C, Doyle HR, Mandala L, Marino IR, Caruana G, Gruttadauria S, Lauro A, Magnone M, Scotti Foglieni C, Lamonaca V, Scott VL. Source: Int J Artif Organs. 2003 October; 26(10): 918-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636008
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Characterization of human xenoreactive antibodies in liver failure patients exposed to pig hepatocytes after bioartificial liver treatment: an ex vivo model of pig to human xenotransplantation. Author(s): Baquerizo A, Mhoyan A, Kearns-Jonker M, Arnaout WS, Shackleton C, Busuttil RW, Demetriou AA, Cramer DV. Source: Transplantation. 1999 January 15; 67(1): 5-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9921790
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Chemically-induced liver failure. Author(s): Van Hoenacker FM, Vandaele L, Kiekens M. Source: J Belge Radiol. 1998 October; 81(5): 252. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9880977
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Cholestasis and liver failure with lambda-AL amyloidosis. Author(s): Konikoff F, Mor C, Stern S, Shaklai M, Halevy J, Theodor E. Source: Gut. 1987 July; 28(7): 903-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3115870
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Chronic copper toxicosis presenting as liver failure in an Australian child. Author(s): Price LA, Walker NI, Clague AE, Pullen ID, Smits SJ, Ong TH, Patrick M. Source: Pathology. 1996 November; 28(4): 316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9007949
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Chronic liver failure induced by long-term administration of tegafur: a case report. Author(s): Matsumoto M, Nakao K, Matsumoto H, Iwata K, Ohta Y, Kanai K, Takahashi K, Akima M. Source: Hepatogastroenterology. 1998 November-December; 45(24): 2372-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9951926
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Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: pathophysiology and management. Author(s): Ellis A, Wendon J. Source: Seminars in Liver Disease. 1996 November; 16(4): 379-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9027951
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Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial. Author(s): Watanabe FD, Mullon CJ, Hewitt WR, Arkadopoulos N, Kahaku E, Eguchi S, Khalili T, Arnaout W, Shackleton CR, Rozga J, Solomon B, Demetriou AA. Source: Annals of Surgery. 1997 May; 225(5): 484-91; Discussion 491-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9193176
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Clinical features of non-Hodgkins lymphoma presenting with acute liver failure: a report of five cases and review of published experience. Author(s): Lettieri CJ, Berg BW. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1641-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873593
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Coagulation disturbances and fulminant liver failure. Author(s): Mowat AP. Source: Archives of Disease in Childhood. 1985 July; 60(7): 686. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4026374
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COX-2 inhibitor (nimesulide) induced acute liver failure. Author(s): Stadlmann S, Zoller H, Vogel W, Offner FA. Source: Virchows Archiv : an International Journal of Pathology. 2002 May; 440(5): 5535. Epub 2002 February 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021934
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Daily hemofiltration for an ADPKD liver failure patient. Author(s): Iorio L, Saltarelli G, Nacca RG, Violi F. Source: Contrib Nephrol. 1995; 115: 154-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8585905
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Dapsone and liver failure. Author(s): Shuster J. Source: Nursing. 1998 January; 28(1): 75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9451224
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Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis. Author(s): Suhler E, Lin W, Yin HL, Lee WM. Source: Critical Care Medicine. 1997 April; 25(4): 594-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9142022
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Decreasing posthepatectomy liver failure. Author(s): Zhou XD, Tang ZY, Yu YQ. Source: Cancer Treat Res. 1994; 69: 307-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8031661
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Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion. Author(s): Fisher RA, Bu D, Thompson M, Tisnado J, Prasad U, Sterling R, Posner M, Strom S. Source: Transplantation. 2000 January 27; 69(2): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10670643
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Delayed neuropsychologic dysfunction after liver transplantation for acute liver failure: a matched, case-controlled study. Author(s): Jackson EW, Zacks S, Zinn S, Ryan J, Johnson MW, Gerber DA, Andreoni K, Fair JH, Shrestha R, Fried MW. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 October; 8(10): 932-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360436
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Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid. Author(s): Durand F, Bernuau J, Pessayre D, Samuel D, Belaiche J, Degott C, Bismuth H, Belghiti J, Erlinger S, Rueff B, et al. Source: Hepatology (Baltimore, Md.). 1995 April; 21(4): 929-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7705802
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Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis. Author(s): Shneider BL, Setchell KD, Whitington PF, Neilson KA, Suchy FJ. Source: The Journal of Pediatrics. 1994 February; 124(2): 234-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8301429
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Detection and monitoring of intracranial pressure dysregulation in liver failure by ultrasound. Author(s): Helmke K, Burdelski M, Hansen HC. Source: Transplantation. 2000 July 27; 70(2): 392-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933171
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Developing a World view toward acute liver failure. Author(s): Lee WM, Sorrell MF. Source: Hepatology (Baltimore, Md.). 1996 July; 24(1): 270-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8707275
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Differential diagnosis of postoperative liver failure in a 12-year-old child. Author(s): Hausmann R, Schmidt B, Schellmann B, Betz P. Source: International Journal of Legal Medicine. 1996; 109(4): 210-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9007637
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Difficult management choices for infants with short bowel syndrome and liver failure. Author(s): Hassan KO, Beath SV, McKiernan PJ, Kelly DA, Clarke SE, Pimpilwar A, Bianchi A, de Ville de Goyet J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 August; 35(2): 216-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187301
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Diffuse hepatic intravascular carcinomatous embolization resulting in fatal liver failure: a clinicopathologic study of 4 cases. Author(s): Begin LR, Boucher D, Lamoureux E. Source: Pathology, Research and Practice. 2001; 197(6): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11432671
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Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure. Author(s): Streetz K, Fregien B, Plumpe J, Korber K, Kubicka S, Sass G, Bischoff SC, Manns MP, Tiegs G, Trautwein C. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 July 1; 167(1): 514-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11418690
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Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia. Author(s): Larsen FS, Adel Hansen B, Pott F, Ejlersen E, Secher NH, Paulson OB, Knudsen GM. Source: Journal of Hepatology. 1996 August; 25(2): 145-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878774
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Does ammonia contribute to increased GABA-ergic neurotransmission in liver failure? Author(s): Jones EA, Basile AS. Source: Metabolic Brain Disease. 1998 December; 13(4): 351-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206826
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Does hypophosphatemia play a role in acute liver failure? Author(s): Knochel JP. Source: Hepatology (Baltimore, Md.). 1989 March; 9(3): 504-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2921001
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D-penicillamine and plasmapheresis in acute liver failure secondary to Wilson's disease. Author(s): Rodriguez Farina E, Tremosa Llurba G, Xiol Quingles X, Lores Obradors A, Castellote Alonso J, Gornals Soler JB, Lopez Nunez C. Source: Rev Esp Enferm Dig. 2003 January; 95(1): 60-2, 63-5. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760731
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Dynamic liver radionuclide scanning in the evaluation of liver failure and portal hypertension in cirrhotic patients. Author(s): Bonazza A, Moro E, Alessandrini P, Gravili S, Bittolo Bon G. Source: J Nucl Biol Med. 1994 March; 38(1): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8075170
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Earlier identification of patients at risk from acetaminophen-induced acute liver failure. Author(s): Mitchell I, Bihari D, Chang R, Wendon J, Williams R. Source: Critical Care Medicine. 1998 February; 26(2): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9468165
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Early-onset liver disease complicated with acute liver failure in Alstrom syndrome. Author(s): Quiros-Tejeira RE, Vargas J, Ament ME. Source: American Journal of Medical Genetics. 2001 June 1; 101(1): 9-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343329
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East meets West: acute liver failure in the global village. Author(s): Bowen DG, Shackel NA, McCaughan GW. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15(5): 467-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10847429
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Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure. Author(s): Clemmesen JO, Kondrup J, Nielsen LB, Larsen FS, Ott P. Source: The American Journal of Gastroenterology. 2001 April; 96(4): 1217-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11316173
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Effects of liver failure on the enzymes in the branched-chain amino acid catabolic pathway. Author(s): Shimomura Y, Honda T, Goto H, Nonami T, Kurokawa T, Nagasaki M, Murakami T. Source: Biochemical and Biophysical Research Communications. 2004 January 9; 313(2): 381-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684172
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Efficacy of hepatic arterial infusion of prostaglandin E1 in the treatment of postoperative acute liver failure--report of a case. Author(s): Sato T, Asanuma Y, Hashimoto M, Heianna J, Kusano T, Kurokawa T, Yasui O, Koyama K. Source: Hepatogastroenterology. 2000 May-June; 47(33): 846-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10919045
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Elevated anticardiolipin antibodies in acute liver failure. Author(s): Rozee KR, Acott P, Lee SH, Crocker JF, Gough D, MacDonald J, Evans J, Murphy MG. Source: Biochimica Et Biophysica Acta. 2003 April 17; 1637(3): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697298
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Erythropoietic protoporphyria with fatal liver failure. Author(s): Ishibashi A, Ogata R, Sakisaka S, Kumashiro R, Koga Y, Mitsuyama K, Kuromatsu R, Uchimura Y, Ijyuin H, Tanaka K, Iwao T, Ishii K, Sata M, Inoue Y, Kin Y, Oizumi K, Nishida H, Imaizumi T, Tanikawa K. Source: Journal of Gastroenterology. 1999 June; 34(3): 405-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10433022
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Etiology and outcome for 295 patients with acute liver failure in the United States. Author(s): Schiodt FV, Atillasoy E, Shakil AO, Schiff ER, Caldwell C, Kowdley KV, Stribling R, Crippin JS, Flamm S, Somberg KA, Rosen H, McCashland TM, Hay JE, Lee WM. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1999 January; 5(1): 29-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9873089
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Etiology and outcome of acute liver failure: experience from a liver transplantation centre in Montreal. Author(s): Tessier G, Villeneuve E, Villeneuve JP. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2002 October; 16(10): 672-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12420024
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Evaluation of acute liver failure. Author(s): Krogstad P, Martin MG. Source: The Pediatric Infectious Disease Journal. 2003 September; 22(9): 831-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506378
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Experiences with MARS liver support therapy in liver failure: analysis of 176 patients of the International MARS Registry. Author(s): Steiner C, Mitzner S. Source: Liver. 2002; 22 Suppl 2: 20-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220298
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Extracorporeal albumin dialysis in acute-on-chronic liver failure: will it stand the test of time? Author(s): Sen S, Jalan R, Williams R. Source: Hepatology (Baltimore, Md.). 2002 October; 36(4 Pt 1): 1014-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297853
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Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure. Author(s): Mitzner SR, Stange J, Klammt S, Peszynski P, Schmidt R, Noldge-Schomburg G. Source: Journal of the American Society of Nephrology : Jasn. 2001 February; 12 Suppl 17: S75-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11251037
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Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review of world experience. Author(s): Pascher A, Sauer IM, Hammer C, Gerlach JC, Neuhaus P. Source: Xenotransplantation. 2002 September; 9(5): 309-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12199863
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Extracorporeal liver perfusion using human and pig livers for acute liver failure. Author(s): Horslen SP, Hammel JM, Fristoe LW, Kangas JA, Collier DS, Sudan DL, Langnas AN, Dixon RS, Prentice ED, Shaw BW Jr, Fox IJ. Source: Transplantation. 2000 November 27; 70(10): 1472-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11118093
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Extracorporeal liver support with MARS in liver failure: has it a role in the treatment of severe alcoholic hepatitis? Author(s): Ann Intern Med. 2002 Dec 17;137(12):I24 Source: Journal of Hepatology. 2003 January; 38(1): 104-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484742
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Extracorporeal methods of liver failure treatment. Author(s): Yamazaki Z, Kanai F, Idezuki Y, Inoue N. Source: Biomater Artif Cells Artif Organs. 1987-88; 15(4): 667-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3452424
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Extracorporeal perfusion for the treatment of acute liver failure. Author(s): Stockmann HB, Hiemstra CA, Marquet RL, IJzermans JN. Source: Annals of Surgery. 2000 April; 231(4): 460-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10749605
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Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis. Author(s): Riordan SM, Williams R. Source: Journal of Gastroenterology and Hepatology. 1999 August; 14(8): 757-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10482426
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Fatal cholestatic liver failure associated with gemcitabine therapy. Author(s): Robinson K, Lambiase L, Li J, Monteiro C, Schiff M. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1804-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561005
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Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient with severe thyroid eye disease. Author(s): Weissel M, Hauff W. Source: Thyroid : Official Journal of the American Thyroid Association. 2000 June; 10(6): 521. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10907999
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Fatal liver failure after the administration of raltitrexed for cancer chemotherapy: a report of two cases. Author(s): Raderer M, Fiebiger W, Wrba F, Scheithauer W. Source: Cancer. 2000 August 15; 89(4): 890-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10951354
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Fatal liver failure associated with valproate therapy in a patient with Friedreich's disease: review of valproate hepatotoxicity in adults. Author(s): Konig SA, Schenk M, Sick C, Holm E, Heubner C, Weiss A, Konig I, Hehlmann R. Source: Epilepsia. 1999 July; 40(7): 1036-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403231
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Fatal liver failure due to ketoconazole treatment of a girl with Cushing's syndrome. Author(s): Zollner E, Delport S, Bonnici F. Source: J Pediatr Endocrinol Metab. 2001 March; 14(3): 335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11308052
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Fatal liver failure in haemophiliacs with HIV-induced immunodeficiency: observation of six patients. Author(s): Toyoda H, Fukuda Y, Nakano I, Katano Y, Takamatsu J, Saito H, Hayakawa T. Source: Haemophilia : the Official Journal of the World Federation of Hemophilia. 1999 March; 5(2): 109-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10215959
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Fatal portal hypertension, liver failure, and mitochondrial dysfunction after HIV-1 nucleoside analogue-induced hepatitis and lactic acidaemia. Author(s): Carr A, Morey A, Mallon P, Williams D, Thorburn DR. Source: Lancet. 2001 May 5; 357(9266): 1412-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11356442
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Favorable nutritional outcome after isolated liver transplantation for liver failure in a child with short bowel syndrome. Author(s): Gottrand F, Michaud L, Bonnevalle M, Dubar G, Pruvot FR, Turck D. Source: Transplantation. 1999 February 27; 67(4): 632-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10071040
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Favorable outcome of orthotopic liver transplantation in a patient with subacute liver failure due to the emergence of a hepatitis B YMDD escape mutant virus. Author(s): Starkel P, Horsmans Y, Geubel A, Ciccarelli O, Goubau P, Rahier J, Lerut J. Source: Journal of Hepatology. 2001 November; 35(5): 679-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11690717
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Favorable response to treatment of a child with T-cell-rich large B-cell lymphoma presenting with liver failure. Author(s): Sathiapalan RK, Hainau B, Al-Mane K, Belgaumi AF. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 October; 25(10): 809-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528106
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First clinical experience with Molecular Adsorbent Recirculating System (MARS) in six patients with severe acute on chronic liver failure. Author(s): Mullhaupt B, Kullak-Ublick GA, Ambuhl P, Maggiorini M, Stocker R, Kadry Z, Clavien PA, Renner EL. Source: Liver. 2002; 22 Suppl 2: 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220307
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Fulminant liver failure associated with clarithromycin. Author(s): Tietz A, Heim MH, Eriksson U, Marsch S, Terracciano L, Krahenbuhl S. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 57-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503933
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Fulminant liver failure associated with flutamide therapy for hirsutism. Author(s): Andrade RJ, Lucena MI, Fernandez MC, Suarez F, Montero JL, Fraga E, Hidalgo F. Source: Lancet. 1999 March 20; 353(9157): 983. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10459914
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Fulminant liver failure due to neuroleptic malignant syndrome. Author(s): Kesan SH, Sid R, Adler D, Crausman RS. Source: Medicine and Health, Rhode Island. 2000 May; 83(5): 153-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10874819
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Fulminant liver failure during interferon beta treatment of multiple sclerosis. Author(s): Yoshida EM, Rasmussen SL, Steinbrecher UP, Erb SR, Scudamore CH, Chung SW, Oger JJ, Hashimoto SA. Source: Neurology. 2001 May 22; 56(10): 1416. Erratum In: Neurology 2001 December 11; 57(11): 2153. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11376205
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Fulminant liver failure from acute HCV superinfection in a patient with HIV, HBV, and HDV coinfections. Author(s): Lee K, Smith PT. Source: Aids Read. 2000 July; 10(7): 398, 401. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10932838
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Fulminant liver failure in a child with invasive group A streptococcal infection. Author(s): Biesel-Desthieux MN, Tissieres P, Belli DC, Le Coultre C, Gervaix A, Masserey Spicher V. Source: European Journal of Pediatrics. 2003 April; 162(4): 245-7. Epub 2003 February 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647197
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Fulminant liver failure in a young child following repeated acetaminophen overdosing. Author(s): Bauer M, Babel B, Giesen H, Patzelt D. Source: J Forensic Sci. 1999 November; 44(6): 1299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10582371
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Fulminant liver failure induced by hepatosplenic alphabeta T-cell lymphoma. Author(s): Petersen-Benz C, Hoffmann N, Beckurts T, Goeser T, Steffen HM, Dries V. Source: Zeitschrift Fur Gastroenterologie. 2003 November; 41(11): 1083-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648377
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Fulminant liver failure: is living related liver transplantation justified with respect to donor risk? Author(s): Haussinger D. Source: Transplantation Proceedings. 2003 May; 35(3): 920-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947800
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Galactose elimination capacity as a prognostic index in patients with fulminant liver failure. Author(s): Ranek L, Andreasen PB, Tygstrup N. Source: Gut. 1976 December; 17(12): 959-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1017716
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Gastrointestinal emergencies with marathon-type running: omental infarction with pancreatitis and liver failure with portal vein thrombosis. Author(s): Scobie BA. Source: N Z Med J. 1998 June 12; 111(1067): 211-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9673635
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Glucoregulation in acute liver failure. Author(s): Vilstrup H, Iversen J, Tygstrup N. Source: European Journal of Clinical Investigation. 1986 June; 16(3): 193-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3089815
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Glutamine, myo-inositol, and brain edema in acute liver failure. Author(s): Cordoba J. Source: Hepatology (Baltimore, Md.). 1996 May; 23(5): 1291-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8621171
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Glyburide-induced cholestatic hepatitis and liver failure. Case-report and review of the literature. Author(s): van Basten JP, van Hoek B, Zeijen R, Stockbrugger R. Source: The Netherlands Journal of Medicine. 1992 June; 40(5-6): 305-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1436270
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Glycine conjugation of para-aminobenzoic acid (PABA): a pilot study of a novel prognostic test in acute liver failure in children. Author(s): Lebel S, Nakamachi Y, Hemming A, Verjee Z, Phillips MJ, Furuya KN. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 January; 36(1): 62-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499998
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Graft regeneration and host liver atrophy after auxiliary heterotopic liver transplantation for chronic liver failure. Author(s): Willemse PJ, Ausema L, Terpstra OT, Krenning EP, ten Kate FW, Schalm SW. Source: Hepatology (Baltimore, Md.). 1992 January; 15(1): 54-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1727799
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Granulocyte colony-stimulating factor improves function of neutrophils from patients with acute liver failure. Author(s): Rolando N, Clapperton M, Wade J, Panetsos G, Mufti G, Williams R. Source: European Journal of Gastroenterology & Hepatology. 2000 October; 12(10): 113540. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11057460
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Halothane-induced acute liver failure: continuing occurrence and use of liver transplantation. Author(s): Lo SK, Wendon J, Mieli-Vergani G, Williams R. Source: European Journal of Gastroenterology & Hepatology. 1998 August; 10(8): 635-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9744690
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Hematologic malignancies with extramedullary spread of disease. Case 3. Extra-nodal Hodgkin's disease presenting as rapidly progressive liver failure. Author(s): Olnes M, Alli P, Freedman A, Auster M, Erlich R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 1; 21(9): 1890-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12721270
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Hemochromatosis presenting as acute liver failure after iron supplementation. Author(s): Perez Roldan F, Amigo Echenagusia A, Gonzalez Carro P. Source: The New England Journal of Medicine. 1998 July 23; 339(4): 269-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9687253
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Hemodynamic changes during a single treatment with the molecular adsorbents recirculating system in patients with acute-on-chronic liver failure. Author(s): Schmidt LE, Sorensen VR, Svendsen LB, Hansen BA, Larsen FS. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 December; 7(12): 1034-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753905
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Hepatectomy: preoperative analysis of hepatic function and postoperative liver failure. Author(s): Zimmermann H, Reichen J. Source: Digestive Surgery. 1998; 15(1): 1-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9845555
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Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure. Author(s): Catalina MV, Barrio J, Anaya F, Salcedo M, Rincon D, Clemente G, Banares R. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003; 23 Suppl 3: 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950960
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Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis. Author(s): Clemmesen JO, Gerbes AL, Gulberg V, Hansen BA, Larsen FS, Skak C, Tygstrup N, Ott P. Source: Hepatology (Baltimore, Md.). 1999 February; 29(2): 347-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9918909
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Hepatic expression of hepatocyte growth factor gene mRNA in acute liver failure. Author(s): Harrison P, Gove C, Bomford A. Source: Digestive Diseases and Sciences. 2000 October; 45(10): 1913-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11117560
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Hepatic outflow obstruction and liver failure due to leukemic cell infiltration in chronic lymphocytic leukemia. Author(s): Costa F, Choy CG, Seiter K, Hann L, Thung SN, Michaeli J. Source: Leukemia & Lymphoma. 1998 July; 30(3-4): 403-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9713971
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Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood. Author(s): Wolber EM, Ganschow R, Burdelski M, Jelkmann W. Source: Hepatology (Baltimore, Md.). 1999 June; 29(6): 1739-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10347116
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Hepatitis B infection in patients with acute liver failure in the United States. Author(s): Teo EK, Ostapowicz G, Hussain M, Lee WM, Fontana RJ, Lok AS; US ALF Study Group (Acute Liver Failure). Source: Hepatology (Baltimore, Md.). 2001 April; 33(4): 972-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11283862
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Hepatitis E-associated subacute liver failure: a rare indication for liver transplantation. Author(s): Nicoluzzi J, Mennecier D, Sogni P, Soubrane O, Chaussade S, Cardoso J, Calmus Y. Source: The American Journal of Gastroenterology. 2001 July; 96(7): 2278-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467680
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Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation. Author(s): Locasciulli A, Bruno B, Alessandrino EP, Meloni G, Arcese W, Bandini G, Cassibba V, Rotoli B, Morra E, Majolino I, Alberti A, Bacigalupo A; Italian Cooperative Group for Blood and Marrow Transplantation. Source: Bone Marrow Transplantation. 2003 February; 31(4): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621466
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Hepatocyte proliferation in health and in liver failure. Author(s): Rozga J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 February; 8(2): Ra32-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11859294
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High-volume plasmaexchange: an effective tool in acute liver failure treatment. Author(s): Mazzoni A, Pardi C, Bortoli M, Uncini Manganelli C, Vanacore R, Urciuoli P, Biancofiore G, Bindi L, Urbani L, Filipponi F, Scatena F. Source: Int J Artif Organs. 2002 August; 25(8): 814-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12296467
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Human herpesvirus-6 and acute liver failure. Author(s): Harma M, Hockerstedt K, Lautenschlager I. Source: Transplantation. 2003 August 15; 76(3): 536-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923440
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Hyperbaric oxygenation, plasma exchange, and hemodialysis for treatment of acute liver failure in a 3-year-old child. Author(s): Ponikvar R, Buturovic J, Cizman M, Mekjavic I, Kandus A, Premru V, Urbancic A, Zakotnik B, Bren A, Ivanovich P. Source: Artificial Organs. 1998 November; 22(11): 952-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9821529
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Hyperlactatemia in acute liver failure: decreased clearance versus increased production. Author(s): Mizock BA. Source: Critical Care Medicine. 2001 November; 29(11): 2225-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11700431
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Hypothermia for the management of intracranial hypertension in acute liver failure. Author(s): Jalan R, Davies NA, Damink SW. Source: Metabolic Brain Disease. 2002 December; 17(4): 437-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602519
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Hypothermia for the management of intracranial hypertension in acute liver failure. Author(s): Jalan R, Olde Damink SW. Source: Current Opinion in Critical Care. 2001 August; 7(4): 257-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11571423
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Idiosyncratic drug allergic phenprocoumon-induced hepatitis with subacute liver failure initially misdiagnosed as autoimmune hepatitis. Author(s): Hinrichsen H, Luttges J, Kloppel G, Folsch UR, Schmidt WE. Source: Scandinavian Journal of Gastroenterology. 2001 July; 36(7): 780-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11444480
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Images of the brain in chronic liver failure. Author(s): Butterworth RF. Source: Journal of Hepatology. 2001 November; 35(5): 661-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11690714
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Immunization and the decline of viral hepatitis as a cause of acute liver failure. Author(s): Sjogren M. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 554-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12939580
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Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization. Author(s): Sawyer RG, McGory RW, Gaffey MJ, McCullough CC, Shephard BL, Houlgrave CW, Ryan TS, Kuhns M, McNamara A, Caldwell SH, Abdulkareem A, Pruett TL. Source: Annals of Surgery. 1998 June; 227(6): 841-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9637547
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Improvement in central nervous system functions during treatment of liver failure with albumin dialysis MARS--a review of clinical, biochemical, and electrophysiological data. Author(s): Mitzner S, Loock J, Peszynski P, Klammt S, Majcher-Peszynska J, Gramowski A, Stange J, Schmidt R. Source: Metabolic Brain Disease. 2002 December; 17(4): 463-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602522
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In vivo estimation of bioartificial liver with recombinant HepG2 cells using pigs with ischemic liver failure. Author(s): Enosawa S, Miyashita T, Fujita Y, Suzuki S, Amemiya H, Omasa T, Hiramatsu S, Suga K, Matsumura T. Source: Cell Transplantation. 2001; 10(4-5): 429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549067
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Inadvertent diclofenac rechallenge from generic and non-generic prescribing, leading to liver transplantation for fulminant liver failure. Author(s): Greaves RR, Agarwal A, Patch D, Davies SE, Sherman D, Reynolds N, Rolles K, Davidson BR, Burroughs AK. Source: European Journal of Gastroenterology & Hepatology. 2001 January; 13(1): 71-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204815
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Inappropriate pemoline therapy leading to acute liver failure and liver transplantation. Author(s): Abbiati C, Vecchi M, Rossi G, Donata MF, de Franchis R. Source: Dig Liver Dis. 2002 June; 34(6): 447-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12132793
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Incidence of idiopathic acute liver failure and hospitalized liver injury in patients treated with troglitazone. Author(s): Graham DJ, Drinkard CR, Shatin D. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526954
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Increased risk of chronic liver failure in adults with heterozygous alpha1-antitrypsin deficiency. Author(s): Graziadei IW, Joseph JJ, Wiesner RH, Therneau TM, Batts KP, Porayko MK. Source: Hepatology (Baltimore, Md.). 1998 October; 28(4): 1058-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755243
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Increased serum soluble Fas in patients with acute liver failure due to paracetamol overdose. Author(s): Tagami A, Ohnishi H, Hughes RD. Source: Hepatogastroenterology. 2003 May-June; 50(51): 742-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828076
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Infection and the progression of hepatic encephalopathy in acute liver failure. Author(s): Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT. Source: Gastroenterology. 2003 September; 125(3): 755-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949721
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Insulin sensitivity and beta-cell secretion after liver transplantation in patients with acute liver failure. Author(s): Konrad T, Golling M, Vicini P, Toffolo G, Wittman M, Mahon A, Klar E, Cobelli C, Usadel K. Source: Transplantation Proceedings. 2001 June; 33(4): 2576-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406252
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Intensive care management of patients with acute liver failure with emphasis on systemic hemodynamic instability and cerebral edema: a critical appraisal of pathophysiology. Author(s): Larsen FS, Hansen BA, Blei AT. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 November; 14 Suppl D: 105D-111D. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110622
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Interorgan ammonia metabolism in liver failure. Author(s): Olde Damink SW, Deutz NE, Dejong CH, Soeters PB, Jalan R. Source: Neurochemistry International. 2002 August-September; 41(2-3): 177-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12020618
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Intestinal endotoxemia as a pathogenetic mechanism in liver failure. Author(s): Han DW. Source: World Journal of Gastroenterology : Wjg. 2002 December; 8(6): 961-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439906
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Intracranial hypertension in acute liver failure. Author(s): Richardson D, Bellamy M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 January; 17(1): 23-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773457
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Intracranial hypertension in acute liver failure: pathophysiological basis of rational management. Author(s): Jalan R. Source: Seminars in Liver Disease. 2003 August; 23(3): 271-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523680
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Investigation of SEN virus infection in patients with cryptogenic acute liver failure, hepatitis-associated aplastic anemia, or acute and chronic non-A-E hepatitis. Author(s): Umemura T, Tanaka E, Ostapowicz G, Brown KE, Heringlake S, Tassopoulos NC, Wang RY, Yeo AE, Shih JW, Orii K, Young NS, Hatzakis A, Manns MP, Lee WM, Kiyosawa K, Alter HJ. Source: The Journal of Infectious Diseases. 2003 November 15; 188(10): 1545-52. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624381
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Is there a point at which you would recommend discontinuing treatment due to liver toxicity, short of liver failure? What, for instance, would be the numbers to look for with liver enzyme tests? How high is too high? My doctor has said they are seeing more people in their practice die from liver disorders than from the virus itself nowadays. This has me very concerned since I am co-infected with HCV. Author(s): Sulkowski MS. Source: Hopkins Hiv Rep. 2001 November; 13(6): 11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11727414
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Jaundice, hepatosplenomegaly and liver failure in a 60-year-old woman. Author(s): Campisi DJ, McElroy CR, Criley JM, Gilkey F. Source: The Western Journal of Medicine. 1981 January; 134(1): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7210660
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Keratin, fas, and cryptogenic liver failure. Author(s): Sorom AJ, Nyberg SL, Gores GJ. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 December; 8(12): 1195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12474161
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Left hepatic vein kinking after right trisegmentectomy: a potential cause of postoperative liver failure. Author(s): Poon RT, Chan J, Fan ST. Source: Hepatogastroenterology. 1998 March-April; 45(20): 508-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9638438
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Lethal liver failure in an elderly patient with hepatitis B superinfected with EpsteinBarr virus. Author(s): Jimenez-Saenz M, Perez-Pozo JM, Leal-Luna A, Herrerias-Gutierrez JM. Source: European Journal of Gastroenterology & Hepatology. 2002 November; 14(11): 1283-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439128
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Live-donor liver transplantation for acute-on-chronic hepatitis B liver failure. Author(s): Liu CL, Fan ST, Lo CM, Wei WI, Yong BH, Lai CL, Wong J. Source: Transplantation. 2003 October 27; 76(8): 1174-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578749
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Liver failure and peripheral facial paralysis in a case of primary amyloidosis. Author(s): Ruiz-Laiglesia F, Perez-Calvo JI, Torrubia-Perez CB, Castiella-Muruzabal T, Morandeira-Garcia MJ. Source: Archives of Internal Medicine. 1998 October 12; 158(18): 2066-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9778208
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Liver failure associated with mitochondrial DNA depletion. Author(s): Morris AA, Taanman JW, Blake J, Cooper JM, Lake BD, Malone M, Love S, Clayton PT, Leonard JV, Schapira AH. Source: Journal of Hepatology. 1998 April; 28(4): 556-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9566823
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Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mitochondrial DNA depletion. Author(s): Herraiz M, Beraza N, Solano A, Sangro B, Montoya J, Qian C, Prieto J, Bustos M. Source: Human Gene Therapy. 2003 March 20; 14(5): 463-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691611
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Liver failure in a child receiving highly active antiretroviral therapy and voriconazole. Author(s): Scherpbier HJ, Hilhorst MI, Kuijpers TW. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 828-30. Epub 2003 August 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955645
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Liver failure in a neonate with congenital adrenal hyporesponsiveness. Author(s): Cheung M, Bansal S, Aw MM, Buchanan CR, Mieli-Vergani G, Dhawan A. Source: European Journal of Pediatrics. 2003 July; 162(7-8): 558. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12802686
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Liver failure in adult Still's disease during corticosteroid treatment. Author(s): Ott SJ, Baron A, Berghaus T, Lamerz R, Beuers U. Source: European Journal of Gastroenterology & Hepatology. 2003 January; 15(1): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544700
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Liver failure in protoporphyria: long-term treatment with oral charcoal. Author(s): Gorchein A, Foster GR. Source: Hepatology (Baltimore, Md.). 1999 March; 29(3): 995-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10189233
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Liver failure, transplantation, and critical care. Author(s): Krasko A, Deshpande K, Bonvino S. Source: Critical Care Clinics. 2003 April; 19(2): 155-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12699318
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Liver failure: basis of benefit of therapy with the molecular adsorbents recirculating system. Author(s): Sen S, Jalan R, Williams R. Source: The International Journal of Biochemistry & Cell Biology. 2003 September; 35(9): 1306-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798344
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Liver support in acute liver failure. Author(s): Hughes RD. Source: Wiener Klinische Wochenschrift. 2003 September 15; 115(15-16): 547-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531165
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Liver support in fulminant liver failure after hemorrhagic shock. Author(s): Faybik P, Hetz H, Krenn CG, Baker A, Germann P, Berlakovich G, Steininger R, Steltzer H. Source: Wiener Klinische Wochenschrift. 2003 September 15; 115(15-16): 595-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531174
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Liver transplantation for acute liver failure--better safe than sorry. Author(s): Schiodt FV, Lee WM. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 November; 8(11): 1063-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424721
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Liver transplantation for fulminant liver failure in children. Author(s): Mondragon R, Mieli-Vergani G, Heaton ND, Mowat AP, Vougas V, Williams R, Tan KC. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S206-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621778
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Liver transplantation in acute liver failure. Author(s): Higgins PD, Fontana RJ. Source: Panminerva Medica. 2003 June; 45(2): 85-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855932
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Living related heterotopic auxiliary partial liver transplantation for extremely smallfor-size graft in fulminant liver failure. Author(s): Sato Y, Yamamoto S, Takeishi T, Kobayashi T, Kato T, Watanabe T, Shimamura T, Ichida T, Hatakeyama K. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1220-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571703
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Living related liver transplantation for acute liver failure in children. Author(s): Emre S, Schwartz ME, Shneider B, Hojsak J, Kim-Schluger L, Fishbein TM, Guy SR, Sheiner PA, LeLeiko NS, Birnbaum A, Suchy FJ, Miller CM. Source: Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1999 May; 5(3): 161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226105
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Long-term treatment of patients with acute exacerbation of chronic liver failure by albumin dialysis. Author(s): Seige M, Kreymann B, Jeschke B, Schweigart U, Kopp KF, Classen M. Source: Transplantation Proceedings. 1999 February-March; 31(1-2): 1371-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10083608
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Malarial liver failure: myth or reality? Author(s): Anand AC. Source: Trop Gastroenterol. 2001 April-June; 22(2): 55-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11552486
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Management of acute liver failure. Author(s): Herrera JL. Source: Digestive Diseases (Basel, Switzerland). 1998 September-October; 16(5): 274-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9892787
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Management of liver failure in a haemophilic patient co-infected with human immunodeficiency and hepatitis C viruses. Author(s): Nitu IC, Lee CA, Dhillon AP, Mistry PK. Source: Clinical and Laboratory Haematology. 1999 April; 21(2): 139-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10342075
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Managing liver failure. Author(s): Kelly DA. Source: Postgraduate Medical Journal. 2002 November; 78(925): 660-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12496321
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MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure. Author(s): Novelli G, Rossi M, Pretagostini R, Poli L, Novelli L, Berloco P, Ferretti G, Iappelli M, Cortesini R. Source: Liver. 2002; 22 Suppl 2: 43-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220303
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MARS treatment in posthepatectomy liver failure. Author(s): van de Kerkhove MP, de Jong KP, Rijken AM, de Pont AC, van Gulik TM. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003; 23 Suppl 3: 44-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950961
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Measurement of serum hyaluronate as a predictor of human liver failure after major hepatectomy. Author(s): Yachida S, Wakabayashi H, Kokudo Y, Goda F, Okada S, Maeba T, Maeta H. Source: World Journal of Surgery. 2000 March; 24(3): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10658073
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Mechanisms of hepatocyte injury, multiorgan failure, and prognostic criteria in acute liver failure. Author(s): Riordan SM, Williams R. Source: Seminars in Liver Disease. 2003 August; 23(3): 203-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523674
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Metabolic activity and clinical efficacy of animal and human hepatocytes in bioartificial support systems for acute liver failure. Author(s): Riordan SM, Skouteris GG, Williams R. Source: Int J Artif Organs. 1998 June; 21(6): 312-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9714023
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Mild hypothermia in the prevention of brain edema in acute liver failure: mechanisms and clinical prospects. Author(s): Chatauret N, Rose C, Butterworth RF. Source: Metabolic Brain Disease. 2002 December; 17(4): 445-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602520
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Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure. Author(s): Krahenbuhl S, Brandner S, Kleinle S, Liechti S, Straumann D. Source: Liver. 2000 July; 20(4): 346-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10959815
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Mitochondrial DNA depletion, near-fatal metabolic acidosis, and liver failure in an HIV-infected child treated with combination antiretroviral therapy. Author(s): Church JA, Mitchell WG, Gonzalez-Gomez I, Christensen J, Vu TH, Dimauro S, Boles RG. Source: The Journal of Pediatrics. 2001 May; 138(5): 748-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343055
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Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Author(s): Jalan R, Damink SW, Deutz NE, Lee A, Hayes PC. Source: Lancet. 1999 October 2; 354(9185): 1164-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10513710
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Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver transplantation for acute liver failure. Author(s): Jalan R, Olde Damink SW, Deutz NE, Davies NA, Garden OJ, Madhavan KK, Hayes PC, Lee A. Source: Transplantation. 2003 June 27; 75(12): 2034-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829907
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Molecular adsorbant recirculating system in patients with liver failure. Author(s): Lamesch P, Jost U, Schreiter D, Scheibner L, Beier O, Fangmann J, Hauss J. Source: Transplantation Proceedings. 2001 November-December; 33(7-8): 3480-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750489
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Molecular Adsorbent Recirculating System: clinical experience in patients with liver failure based on hepatitis B in China. Author(s): Chen S, Zhang L, Shi Y, Yang X, Wang M. Source: Liver. 2002; 22 Suppl 2: 48-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220304
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Molecular neurobiology of acute liver failure. Author(s): Butterworth RF. Source: Seminars in Liver Disease. 2003 August; 23(3): 251-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523678
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More on serum phosphate and prognosis of acute liver failure. Author(s): Bernal W, Wendon J. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 533-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883501
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Mortality due to liver failure and impact on survival of hepatitis virus infections in HIV-infected patients receiving potent antiretroviral therapy. Author(s): Macias J, Melguizo I, Fernandez-Rivera FJ, Garcia-Garcia A, Mira JA, Ramos AJ, Rivera JM, Pineda JA. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 November; 21(11): 775-81. Epub 2002 November 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12461586
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Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5betareductase, in hepatitis and liver failure in infancy. Author(s): Lemonde HA, Custard EJ, Bouquet J, Duran M, Overmars H, Scambler PJ, Clayton PT. Source: Gut. 2003 October; 52(10): 1494-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970144
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NASH-related liver failure: one hit too many? Author(s): Day CP. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 1872-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190148
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Nefazodone-induced acute liver failure. Author(s): Schirren CA, Baretton G. Source: The American Journal of Gastroenterology. 2000 June; 95(6): 1596-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894614
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Nefazodone-induced liver failure: report of three cases. Author(s): Aranda-Michel J, Koehler A, Bejarano PA, Poulos JE, Luxon BA, Khan CM, Ee LC, Balistreri WF, Weber FL Jr. Source: Annals of Internal Medicine. 1999 February 16; 130(4 Pt 1): 285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10068386
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Neonatal hemochromatosis: the importance of early recognition of liver failure. Author(s): Vohra P, Haller C, Emre S, Magid M, Holzman I, Ye MQ, Iofel E, Shneider BL. Source: The Journal of Pediatrics. 2000 April; 136(4): 537-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10753255
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Neonatal liver failure. Author(s): Shneider BL. Source: Current Opinion in Pediatrics. 1996 October; 8(5): 495-501. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8946131
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Neuroleptic malignant syndrome with severe liver failure. Author(s): Urving SH, Nielsen EW. Source: Acta Anaesthesiologica Scandinavica. 2003 September; 47(8): 1041-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904200
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Neurological improvement during bioartificial liver sessions in patients with acute liver failure awaiting transplantation. Author(s): Samuel D, Ichai P, Feray C, Saliba F, Azoulay D, Arulnaden JL, Debat P, Gigou M, Adam R, Bismuth A, Castaing D, Bismuth H. Source: Transplantation. 2002 January 27; 73(2): 257-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821741
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Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure. Author(s): Clapperton M, Rolando N, Sandoval L, Davies E, Williams R. Source: European Journal of Clinical Investigation. 1997 February; 27(2): 164-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9061311
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New liver support devices in acute liver failure: a critical evaluation. Author(s): Sen S, Williams R. Source: Seminars in Liver Disease. 2003 August; 23(3): 283-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523681
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Nimesulide-induced hepatitis and acute liver failure. Author(s): Weiss P. Source: Isr Med Assoc J. 1999 November; 1(3): 221. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10731347
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Nimesulide-induced hepatitis and acute liver failure. Author(s): Weiss P, Mouallem M, Bruck R, Hassin D, Tanay A, Brickman CM, Farfel Z, Bar-Meir S. Source: Isr Med Assoc J. 1999 October; 1(2): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10731303
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Nimesulide-induced severe hemolytic anemia and acute liver failure leading to liver transplantation. Author(s): Rodrigo L, de Francisco R, Perez-Pariente JM, Cadahia V, Tojo R, Rodriguez M, Lucena MI, Andrade RJ. Source: Scandinavian Journal of Gastroenterology. 2002 November; 37(11): 1341-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12465736
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Nonalcoholic steatohepatitis-related cirrhosis with subacute liver failure: an autopsy case. Author(s): Kuwabara H, Yoshii Y, Mori H, Fujiwara S, Eiraku S, Kojima H, Miyaji K, Hongo Y, Katsu K. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1668-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12924667
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Noncutaneous varicella-zoster virus (VZV) infection with fatal liver failure in a child with acute lymphoblastic leukemia (ALL). Author(s): Muller I, Aepinus C, Beck R, Bultmann B, Niethammer D, Klingebiel T. Source: Medical and Pediatric Oncology. 2001 August; 37(2): 145-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11496356
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Non-Hodgkin lymphoma in pregnancy presenting as acute liver failure. Author(s): Stewart KS, Gordon MC. Source: Obstetrics and Gynecology. 1999 November; 94(5 Pt 2): 847. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546758
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Novel strategies for liver support in acute liver failure. Author(s): Butler A, Friend PJ. Source: British Medical Bulletin. 1997; 53(4): 719-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9536523
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Nursing care of chronic and acute liver failure. Author(s): Starr S, Hand H. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2002 June 19-25; 16(40): 47-54; Quiz 55-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12216300
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Nutrition support for individuals with liver failure. Author(s): Li SD, Lue W, Mobarhan S, Nadir A, Van Thiel DH, Hagerty A. Source: Nutrition Reviews. 2000 August; 58(8): 242-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10946563
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Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer. Author(s): Moriwaki H, Tajika M, Miwa Y, Kato M, Yasuda I, Shiratori Y, Okuno M, Kato T, Ohnishi H, Muto Y. Source: Journal of Gastroenterology. 2000; 35 Suppl 12: 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10779208
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Nutritional support during liver failure. Author(s): Gecelter GR, Comer GM. Source: Critical Care Clinics. 1995 July; 11(3): 675-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7552976
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Orthotopic liver transplantation after subacute liver failure induced by therapeutic doses of ibuprofen. Author(s): Javier Rodriguez-Gonzalez F, Montero JL, Puente J, Fraga E, Costan G, Barrera P, Muntane J, De la Mata M, Zambrana JL. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2476-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358284
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Orthotopic liver transplantation for acute liver failure secondary to autoimmune hepatitis in a child with autoimmune polyglandular syndrome type 1. Author(s): Smith D, Stringer MD, Wyatt J, O'Meara M, Davison S, Cheetham TD, McClean P. Source: Pediatric Transplantation. 2002 April; 6(2): 166-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000475
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Orthotopic liver transplantation with poor neurologic outcome in valproateassociated liver failure: a need for critical risk-benefit appraisal in the use of valproate. Author(s): Thomson MA, Lynch S, Strong R, Shepherd RW, Marsh W. Source: Transplantation Proceedings. 2000 February; 32(1): 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701024
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Outcome of orthotopic liver transplantation in the aetiological and clinical variants of acute liver failure. Author(s): O'Grady JG, Alexander GJ, Thick M, Potter D, Calne RY, Williams R. Source: The Quarterly Journal of Medicine. 1988 October; 68(258): 817-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3268893
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Oxygen delivery to and use by primary porcine hepatocytes in the HepatAssist 2000 system for extracorporeal treatment of patients in end-stage liver failure. Author(s): Custer L, Mullon CJ. Source: Advances in Experimental Medicine and Biology. 1998; 454: 261-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9889900
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Pathogenesis of hepatic encephalopathy in acute liver failure. Author(s): Vaquero J, Chung C, Cahill ME, Blei AT. Source: Seminars in Liver Disease. 2003 August; 23(3): 259-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523679
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Pathologic quiz case: a 35-year old woman with a history of arrhythmia and liver failure. Author(s): Mikolaenko I, Conner MG. Source: Archives of Pathology & Laboratory Medicine. 2002 June; 126(6): 751-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087973
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Phosphorus ans an early predictive factor in patients with acute liver failure. Author(s): Baquerizo A, Anselmo D, Shackleton C, Chen TW, Cao C, Weaver M, Gornbein J, Geevarghese S, Nissen N, Farmer D, Demetriou A, Busuttil RW. Source: Transplantation. 2003 June 27; 75(12): 2007-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829902
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Plasma cytokine levels and coagulation and complement activation during use of the extracorporeal liver assist device in acute liver failure. Author(s): Hughes RD, Nicolaou N, Langley PG, Ellis AJ, Wendon JA, Williams R. Source: Artificial Organs. 1998 October; 22(10): 854-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9790083
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Polyacrylonitrile membrane interposition between a xenograft and a patient in fulminant liver failure: the concept of xenohemodiafiltration in clinical practice. Author(s): Argibay PF, Hyon SH, Martinez-Garbino J, Vazquez JC, Rosa-Diez G, Pekoli J, Macias S, Nunez F, Gadano A. Source: Asaio Journal (American Society for Artificial Internal Organs : 1992). 2000 JulyAugust; 46(4): 505-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10926155
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Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume. Author(s): Shirabe K, Shimada M, Gion T, Hasegawa H, Takenaka K, Utsunomiya T, Sugimachi K. Source: Journal of the American College of Surgeons. 1999 March; 188(3): 304-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10065820
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Postoperative liver failure. Author(s): Bilimoria MM, Chaoui AS, Vauthey JN. Source: Journal of the American College of Surgeons. 1999 September; 189(3): 336-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10472939
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Presence of active hepatitis associated with liver cirrhosis is a risk factor for mortality caused by posthepatectomy liver failure. Author(s): Eguchi H, Umeshita K, Sakon M, Nagano H, Ito Y, Kishimoto SI, Dono K, Nakamori S, Takeda T, Gotoh M, Wakasa K, Matsuura N, Monden M. Source: Digestive Diseases and Sciences. 2000 July; 45(7): 1383-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961718
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Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Author(s): Kobayashi N, Fujiwara T, Westerman KA, Inoue Y, Sakaguchi M, Noguchi H, Miyazaki M, Cai J, Tanaka N, Fox IJ, Leboulch P. Source: Science. 2000 February 18; 287(5456): 1258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10678831
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Primary amyloidosis with liver failure and acute renal failure treated with emergency living-related liver transplantation: a case report. Author(s): Kobayashi T, Sato Y, Ichida T, Ito S, Yamamoto S, Oya H, Sato D, Gejo T, Hatakeyama K. Source: Transplantation Proceedings. 2003 February; 35(1): 356-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591438
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Primary amyloidosis with spontaneous splenic rupture, cholestasis, and liver failure treated with emergency liver transplantation. Author(s): Sandberg-Gertzen H, Ericzon BG, Blomberg B. Source: The American Journal of Gastroenterology. 1998 November; 93(11): 2254-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9820409
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Profound ionized hypomagnesemia induced by therapeutic plasma exchange in liver failure patients. Author(s): Kamochi M, Aibara K, Nakata K, Murakami M, Nandate K, Sakamoto H, Sata T, Shigematsu A. Source: Transfusion. 2002 December; 42(12): 1598-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12473141
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Prognostic value of abdominal CT scanning and hepatic histopathology in patients with acute liver failure. Author(s): Shakil AO, Jones BC, Lee RG, Federle MP, Fung JJ, Rakela J. Source: Digestive Diseases and Sciences. 2000 February; 45(2): 334-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10711447
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Progress in adult liver transplantation for acute liver failure. Author(s): Lerut J, Ciccarelli O, Roggen F, De Kock M, Reding R, Otte JB, Geubel AP, Reynaert MS, Laterre PF. Source: Transplantation Proceedings. 2000 December; 32(8): 2704-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11134769
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Prolongation of the QT interval in children with liver failure. Author(s): Fishberger SB, Pittman NS, Rossi AF. Source: Clin Cardiol. 1999 October; 22(10): 658-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526691
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Prostaglandin E(1) continuous hepatic arterial infusion in the treatment of postoperative acute liver failure: basic study on hepatic hemodynamics and clinical application. Author(s): Sato T, Asanuma Y, Kurokawa T, Kato T, Yasui O, Kusano T, Koyama K. Source: Digestive Surgery. 2000; 17(3): 234-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10867456
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Pulmonary effects of caval clamping during liver transplantation without venovenous bypass in acute or chronic liver failure. Author(s): Valta P, Pere P, Makisalo H, Lindgren L. Source: Transplantation Proceedings. 2001 June; 33(4): 2521-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406234
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Quick correction of hemostasis in two patients with fulminant liver failure undergoing liver transplantation by recombinant activated factor VII. Author(s): Kalicinski P, Kaminski A, Drewniak T, Ismail H, Szymczak M, Markiewicz M, Lukasiewicz H. Source: Transplantation Proceedings. 1999 February-March; 31(1-2): 378-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10083150
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Rapid resolution of brain edema and improved cerebral perfusion pressure following the molecular adsorbent recycling system in acute liver failure patients. Author(s): Ben Abraham R, Szold O, Merhav H, Biderman P, Kidron A, Nakache R, Oren R, Sorkine P. Source: Transplantation Proceedings. 2001 September; 33(6): 2897-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11543780
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Re: Caldwell and Hespenheide--subacute liver failure in obese women. Author(s): Azer SA. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1656-7; Author Reply 1657-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873600
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Recombinant factor VIIa improves coagulopathy caused by liver failure. Author(s): Brown JB, Emerick KM, Brown DL, Whitington PF, Alonso EM. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 September; 37(3): 26872. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960648
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Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Author(s): Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM; U.S. Acute Liver Failure Study Group. Source: Annals of Internal Medicine. 2002 December 17; 137(12): 947-54. Summary for Patients In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484709
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Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy. Author(s): Sharma RA, Decatris MP, Santhanam S, Roy R, Osman AE, Clarke CB, Khanna S, O'Byrne KJ. Source: Cancer Chemotherapy and Pharmacology. 2003 November; 52(5): 367-70. Epub 2003 July 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879281
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Reversible fulminant lactic acidosis and liver failure in an infant with hepatic cytochrome-c oxidase deficiency. Author(s): Lev D, Gilad E, Leshinsky-Silver E, Houri S, Levine A, Saada A, LermanSagie T. Source: Journal of Inherited Metabolic Disease. 2002 September; 25(5): 371-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408186
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Review article: the management of acute liver failure. Author(s): Plevris JN, Schina M, Hayes PC. Source: Alimentary Pharmacology & Therapeutics. 1998 May; 12(5): 405-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9663719
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Review article: the molecular adsorbents recirculating system (MARS) in liver failure. Author(s): Sen S, Mookerjee RP, Davies NA, Williams R, Jalan R. Source: Alimentary Pharmacology & Therapeutics. 2002 December; 16 Suppl 5: 32-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12423451
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Review of methods to remove protein-bound substances in liver failure. Author(s): Hughes RD. Source: Int J Artif Organs. 2002 October; 25(10): 911-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456030
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Risk of unexplained acute liver failure in diabetes mellitus. Author(s): Graham DJ. Source: Archives of Internal Medicine. 2003 November 24; 163(21): 2649-50; Author Reply 2650-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638568
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Sera from liver failure patients and a demethylating agent stimulate transdifferentiation of murine bone marrow cells into hepatocytes in coculture with nonparenchymal liver cells. Author(s): Yamazaki S, Miki K, Hasegawa K, Sata M, Takayama T, Makuuchi M. Source: Journal of Hepatology. 2003 July; 39(1): 17-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821039
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Serum bile acids in patients with liver failure supported with a bioartificial liver. Author(s): Pazzi P, Morsiani E, Vilei MT, Granato A, Rozga J, Demetriou AA, Muraca M. Source: Alimentary Pharmacology & Therapeutics. 2002 August; 16(8): 1547-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182755
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Serum protein S-100b in acute liver failure: Results of the US Acute Liver Failure Study group. Author(s): Vaquero J, Jordano Q, Lee WM, Blei AT; US Acute Liver Failure Study Group. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 August; 9(8): 887-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884207
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Splanchnic circulation and metabolism in patients with acute liver failure. Author(s): Clemmesen O. Source: Dan Med Bull. 2002 August; 49(3): 177-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12238280
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Spontaneous bacterial peritonitis in liver failure. Author(s): Lipka JM, Zibari GB, Dies DF, McMillan RW, Aultman DF, McDonald JC. Source: The American Surgeon. 1998 December; 64(12): 1155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9843334
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Subacute liver failure in obese women. Author(s): Caldwell SH, Hespenheide EE. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2058-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190177
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Successful MARS treatment in severe cholestatic patients with acute on chronic liver failure. Author(s): Campli CD, Gaspari R, Mignani V, Stifano G, Santoliquido A, Verme LZ, Proietti R, Pola P, Silveri NG, Gasbarrini G, Gasbarrini A. Source: Artificial Organs. 2003 June; 27(6): 565-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780511
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Successful orthotopic liver transplantation after trimethoprim-sulfamethoxazole associated fulminant liver failure. Author(s): Zaman F, Ye G, Abreo KD, Latif S, Zibari GB. Source: Clinical Transplantation. 2003 October; 17(5): 461-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703931
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Successful treatment of acute liver failure due to polyarteritis nodosa. Author(s): Empen K, Jung MC, Engelhardt D, Sackmann M. Source: The American Journal of Medicine. 2002 September; 113(4): 349-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12361830
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Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial. Author(s): Schmidt LE, Wang LP, Hansen BA, Larsen FS. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 March; 9(3): 290-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619027
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The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Author(s): Murphy N, Auzinger G, Bernel W, Wendon J. Source: Hepatology (Baltimore, Md.). 2004 February; 39(2): 464-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767999
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The effects of serum from patients with acute liver failure on the growth and metabolism of Hep G2 cells. Author(s): Shi Q, Gaylor JD, Cousins R, Plevris J, Hayes PC, Grant MH. Source: Artificial Organs. 1998 December; 22(12): 1023-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876094
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The neurology of liver failure. Author(s): Lewis M, Howdle PD. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 September; 96(9): 623-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925717
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Thrombotic thrombocytopenic purpura after Ecstasy-induced acute liver failure. Author(s): Schirren CA, Berghaus TM, Sackmann M. Source: Annals of Internal Medicine. 1999 January 19; 130(2): 163. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10068371
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To transplant or not to transplant recurrent hepatitis C and liver failure. Author(s): Forman LM. Source: Clinics in Liver Disease. 2003 August; 7(3): 615-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509530
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Topiramate and fulminant liver failure. Author(s): Bjoro K, Gjerstad L, Bentdal O, Osnes S, Schrumpf E. Source: Lancet. 1998 October 3; 352(9134): 1119. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9798593
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Treatment for postoperative liver failure after major hepatectomy under hepatic total vascular exclusion. Author(s): Asanuma Y, Sato T, Yasui O, Kurokawa T, Koyama K. Source: Journal of Artificial Organs : the Official Journal of the Japanese Society for Artificial Organs. 2003; 6(2): 152-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621697
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Treatment of severe liver failure with a bioartificial liver. Author(s): Chen SC, Mullon C, Kahaku E, Watanabe F, Hewitt W, Eguchi S, Middleton Y, Arkadopoulos N, Rozga J, Solomon B, Demetriou AA. Source: Annals of the New York Academy of Sciences. 1997 December 31; 831: 350-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9616727
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Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure. Author(s): Bernal W, Donaldson P, Underhill J, Wendon J, Williams R. Source: Journal of Hepatology. 1998 July; 29(1): 53-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9696492
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Tyrosinemia type 1 should be suspected in infants with severe coagulopathy even in the absence of other signs of liver failure. Author(s): Croffie JM, Gupta SK, Chong SK, Fitzgerald JF. Source: Pediatrics. 1999 March; 103(3): 675-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10049978
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Unsuccessful rescue therapy with adefovir dipivoxil for lamivudine resistant HBV in a patient with liver failure. Author(s): Thabut D, Ratziu V, Bernard-Chabert B, Poynard T, Benhamou Y, Thibault V. Source: Gut. 2003 April; 52(4): 614. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631687
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Unusual electronmicroscopic changes in valproate-associated liver failure. Author(s): Caparros-Lefebvre D, Lecomte-Houcke M, Pruvot FR, Declerck N, Paris JC, Petit H. Source: Lancet. 1993 June 19; 341(8860): 1604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8099687
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Unusual peripheral T cell lymphoma presenting as acute liver failure and reappearing in the liver allograft. Author(s): Blakolmer K, Gaulard P, Mannhalter C, Swerdlow S, Fassati LR, Rossi G, Maggi U, Conte D, Demetris AJ. Source: Transplantation. 2000 December 27; 70(12): 1802-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11152113
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Use and outcome of liver transplantation in acetaminophen-induced acute liver failure. Author(s): Bernal W, Wendon J, Rela M, Heaton N, Williams R. Source: Hepatology (Baltimore, Md.). 1998 April; 27(4): 1050-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9537445
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Use and validation of selection criteria for liver transplantation in acute liver failure. Author(s): Riordan SM, Williams R. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 March; 6(2): 170-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10719015
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Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver failure. Author(s): Kojima H, Kaita KD, Hawkins K, Uhanova J, Minuk GY. Source: Antimicrobial Agents and Chemotherapy. 2002 October; 46(10): 3280-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234860
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Use of MARS in the treatment of acute liver failure: preliminar monocentric experience. Author(s): Novelli G, Rossi M, Pretagostini R, Poli L, Peritore D, Berloco P, Di Nicuolo A, Iappelli M, Cortesini R. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1942-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267580
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Usefulness of exchange transfusion in acute liver failure due to severe falciparum malaria. Author(s): Ayyub M, Barlas S, Lubbad E. Source: The American Journal of Gastroenterology. 2000 March; 95(3): 802-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710080
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Usefulness of plasma exchange plus continuous hemodiafiltration to reduce adverse effects associated with plasma exchange in patients with acute liver failure. Author(s): Sadahiro T, Hirasawa H, Oda S, Shiga H, Nakanishi K, Kitamura N, Hirano T. Source: Critical Care Medicine. 2001 July; 29(7): 1386-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11445692
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Utility of hepatic phosphorus-31 magnetic resonance spectroscopy in a rat model of acute liver failure. Author(s): Corbin IR, Buist R, Peeling J, Zhang M, Uhanova J, Minuk GK. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2003 February; 51(1): 42-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580320
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Valproate-induced liver failure in one of two siblings with Alpers disease. Author(s): Schwabe MJ, Dobyns WB, Burke B, Armstrong DL. Source: Pediatric Neurology. 1997 May; 16(4): 337-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9258971
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Varicella-Zoster virus infection associated with acute liver failure. Author(s): Vartian CV. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 February; 28(2): 412-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10064269
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Varicella-zoster virus infection associated with acute liver failure. Author(s): Dits H, Frans E, Wilmer A, Van Ranst M, Fevery J, Bobbaers H. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 July; 27(1): 209-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9675478
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Viral causes and management of acute liver failure. Author(s): Tibbs C, Williams R. Source: Journal of Hepatology. 1995; 22(1 Suppl): 68-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7602081
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Viral hepatitis-related acute liver failure. Author(s): Schiodt FV, Davern TJ, Shakil AO, McGuire B, Samuel G, Lee WM. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 448-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591067
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Von Willebrand factor could be an index of endothelial dysfunction in patients with cirrhosis: relationship to degree of liver failure and nitric oxide levels. Author(s): Albornoz L, Alvarez D, Otaso JC, Gadano A, Salviu J, Gerona S, Sorroche P, Villamil A, Mastai R. Source: Journal of Hepatology. 1999 March; 30(3): 451-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10190728
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Wilson's disease and liver failure in childhood. Author(s): Sagen E, Lange O, Westgaard G, Bland J, Romslo I. Source: Acta Pharmacol Toxicol (Copenh). 1986; 59 Suppl 7: 236-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3776570
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Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy. Author(s): Shawcross DL, Davies NA, Mookerjee RP, Hayes PC, Williams R, Lee A, Jalan R. Source: Hepatology (Baltimore, Md.). 2004 February; 39(2): 471-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768000
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Xenoantibody response of patients with severe acute liver failure exposed to porcine antigens following treatment with a bioartificial liver. Author(s): Baquerizo A, Mhoyan A, Shirwan H, Swensson J, Busuttil RW, Demetriou AA, Cramer DV. Source: Transplantation Proceedings. 1997 February-March; 29(1-2): 964-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9123610
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Xenotransplantation of immortalized human hepatocytes for experimental acute liver failure in rats. Author(s): Kobayashi N, Noguchi H, Fujiwara T, Tanaka N. Source: Transplantation Proceedings. 2000 August; 32(5): 1123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936390
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CHAPTER 2. NUTRITION AND LIVER FAILURE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and liver failure.
Finding Nutrition Studies on Liver 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 “liver failure” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on liver failure: •
Nutrition support for individuals with liver failure. Author(s): Division of Gastroenterology, Hepatology, and Nutrition, Loyola University Medical Center, Maywood, IL 60153, USA. Source: Li, S D Lue, W Mobarhan, S Nadir, A Van Thiel, D H Hagerty, A NutrRevolume 2000 August; 58(8): 242-7 0029-6643
The following information is typical of that found when using the “Full IBIDS Database” to search for “liver failure” (or a synonym): •
1,8-cineole protects against liver failure in an in-vivo murine model of endotoxemic shock. Author(s): Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Brazil. Source: Santos, F A Silva, R M Tome, A R Rao, V S Pompeu, M M Teixeira, M J De Freitas, L A De Souza, V L J-Pharm-Pharmacol. 2001 April; 53(4): 505-11 0022-3573
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Artificial liver support devices for fulminant liver failure. Author(s): Department of Transplantation, California Pacific Medical Center, San Francisco, USA. Source: Sechser, A Osorio, J Freise, C Osorio, R W Clin-Liver-Dis. 2001 May; 5(2): 415-30 1089-3261
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Continuous arterial infusion of prostaglandin E(1) via the superior mesenteric artery in the treatment of postoperative liver failure. Author(s): College of Allied Medical Science, Akita University, Hondo, Akita, Japan. Source: Asanuma, Yoshihiro Sato, Tsutomu Kato, Takeshi Nanjo, Hiroshi Kurokawa, Toshiaki Yasui, Ouki Koyama, Kenji Ther-Apher. 2002 February; 6(1): 89-92 1091-6660
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Effects of intraperitoneal transplantation of microcarrier-attached hepatocytes on Dgalactosamine-induced acute liver failure in rats. Author(s): First Department of Internal Medicine, Gifu University School of Medicine, Japan. Source: Nagaki, M Kano, T Muto, Y Yamada, T Ohnishi, H Moriwaki, H GastroenterolJpn. 1990 February; 25(1): 78-87 0435-1339
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Effects of prostaglandin E(1) on the efficacy of xenogeneic extracorporeal pig liver perfusion in a canine model of acute liver failure. Author(s): Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
[email protected] Source: Takeyama, O Ikai, I Yagi, T Satoh, S Kanazawa, A Uesugi, T Nishitai, R Okabe, H Katsura, N Terajima, H Yamaoka, Y Liver-Transpl. 2001 June; 7(6): 526-32 1527-6465
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Inappropriate liver transplantation in a child with Alpers-Huttenlocher syndrome misdiagnosed as valproate-induced acute liver failure. Author(s): Department of Pediatric Surgery, Hopital Timone-Enfants, Marseille, France. Source: Delarue, A Paut, O Guys, J M Montfort, M F Lethel, V Roquelaure, B Pellissier, J F Sarles, J Camboulives, J Pediatr-Transplant. 2000 February; 4(1): 67-71 1397-3142
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Protective effect of pretreatment with low-dose lipopolysaccharide on Dgalactosamine-induced acute liver failure. Author(s): Second Department of Surgery, Asahikawa Medical College, Hokkaido, Japan.
[email protected]
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Source: Kono, T Kotani, H Asama, T Mamiya, N Ohara, K Yoneda, M Iwamoto, J Kasai, S Int-J-Colorectal-Dis. 2002 March; 17(2): 98-103 0179-1958
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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to liver 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 Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com
•
Food and Diet High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. CLINICAL TRIALS AND LIVER FAILURE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning liver failure.
Recent Trials on Liver Failure The following is a list of recent trials dedicated to liver failure.8 Further information on a trial is available at the Web site indicated. •
Phase 2 Evaluation of the ELAD System in the Management of Acute Liver Failure Condition(s): Fulminant Hepatic Failure Study Status: This study is currently recruiting patients. Sponsor(s): VitaGen Purpose - Excerpt: The purpose of this study is to determine if treatment with the ELAD Bioartificial Liver Assist Device is beneficial to patients in Acute Liver Failure either as a bridge to liver transplant or bridge to native liver recovery. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030225
•
Prevention of Recurrent Hepatitis B after Liver Transplantation Condition(s): Hepatitis B; Cirrhosis; Acute Liver Failure; Hepatocellular Carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis B accounts for approximately 5000 deaths per year in the United States. Liver transplantation offers the only hope for patients who develop end-
8
These are listed at www.ClinicalTrials.gov.
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stage liver disease. Early results of liver transplantation for hepatitis B were poor with recurrence rate of 80% and 1-year survival of only 50%. Recent studies found that preventive therapy using hepatitis B immune globulin (HBIG) or antiviral medications such as lamivudine can reduce the recurrence rate to roughly 30% with accompanying improvement in survival. However, HBIG when given as intravenous infusion in high doses is very expensive, while long-term use of lamivudine is associated with drug resistance. Some studies found that preventive therapy using both HBIG and lamivudine may decrease recurrence rate to less than 10% but the dose and duration of HBIG needed when used in combination with lamivudine is not clear. Adefovir, a new antiviral medication, is effective against lamivudine resistant hepatitis B but its role in liver transplantation is uncertain because of the risk of kidney damage. Many studies showed that the risk of recurrent hepatitis B is related to the viral load before transplant. Thus, it may be possible to tailor the preventive therapy according to the risk. The aim of this study is to establish the most cost-effective preventive therapy for recurrent hepatitis B after liver transplantation. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059267 •
Randomized Study of Acetylcysteine in Patients with Acute Liver Failure Not Caused by Acetaminophen Condition(s): Acute Liver Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Texas Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of a short course (72 hours) of intravenous acetylcysteine in patients with acute liver failure for whom no antidote or specific treatment is available. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004467
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “liver failure” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical
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trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 4. PATENTS ON LIVER FAILURE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “liver failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on liver failure, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Liver Failure By performing a patent search focusing on liver failure, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on liver failure: •
Artificial liver device Inventor(s): Caperna; Thomas J. (Arnold, MD), Kemp; Christopher W. (Frederick, MD), Powell; Anne M. (Bowie, MD), Pursel; Vernon G. (Highland, MD), Rexroad, Jr.; Caird E. (Gambrills, MD), Talbot; Neil C. (Silver Spring, MD) Assignee(s): The United States of America AS Represented by the Secretary of (washington, Dc) Patent Number: 5,866,420 Date filed: July 1, 1996 Abstract: Continuous cultures of pluripotent parenchymal hepatocytes were derived from the epiblasts of pig blastocysts. The cultures are feeder-dependent and grow slowly with doubling times of 3 to 4 days. They differentiate into large secretory ductlike structures or form small canaliculi. In combination with feeder cells and, optionally, adult pig hepatocytes and macrophages, the cells are useful in an artificial liver device which may be utilized as temporary liver support for the mitigation of the pathological effects of liver failure. Excerpt(s): This invention relates to pluripotent parenchymal hepatocytes derived from the epiblast of pig blastocyst which have been cultured continuously for a number of years, indicating an infinitely self-renewing cell population. The stem cell characteristics of the hepatocytes indicate that the cells are unique for investigations of liver differentiation and organogenesis and are particularly desireable for use in artificial liver devices. Liver transplantation has become widely accepted as an effective treatment for chronic and acute liver disease. One of the major problems associated with the transplantation process, however, as been the need for an effective means for providing temporary support for patients awaiting an available donor organ. Extracorporeal devices for providing heart, kidney and lung support are wellestablished, however, the development of such devices which are effective for liver support has proven more elusive. Two basic approaches have emerged as promising. Both utilize a device such as a hollow fiber cartridge containing liver-derived cells which acts as a perfusion apparatus. Primary hepatocytes attached to microcarriers (Rozga et al. 1993. Hepatology. vol. 17(2), pp. 258-265; Rozga et al. 1994. Ann. Surg. vol. 217(5), pp. 502-511) represents one approach, while transformed cells such as those derived from hepatoblastoma cell lines (Sussman et al. 1992. Hepatology. vol. 16(1), pp. 60-65) are another. These approaches have several drawbacks, however. For example, primary cells have a very limited culture capability, therefore there is a requirement for continuous cell preparation. Transformed cells, on the other hand, grow well in culture, but, since they are transformed, they exhibit functional characteristics which may be different from normal cells. Both also suffer from the lack of accessory cells such as epithelial and bile-duct epithelial cells which are important in the function of a normal liver. The need thus exists for the discovery of normal hepatocytes capable of long-term culture which could effectively mimic liver function in an extracorporal device. Web site: http://www.delphion.com/details?pn=US05866420__
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Hepatoprotective compositions and composition for treatment of conditions related to hepatitis B and E infection Inventor(s): Gupta; Ajaya Prakash (Ghaziabad, IN), Katiyar; Chandra Kant (Ghaziabad, IN), Mehrotra; Raj (Lucknow, IN) Assignee(s): Dabur Research Foundation (ghaziabad, In) Patent Number: 6,136,316 Date filed: April 16, 1997 Abstract: The invention provides a novel polyherbal composition useful for treating acute Hepatitis E virus infection including acute liver failure due to HEV infection, healthy Hepatitis B virus carriers who develop superadded hepatitis E virus infection, acute hepatitis B virus infection, and animal hepadna virus, therapeutic effects on hepatitis B virus infection and also used as a hepatoprotective agent, said composition comprising essentially extracts of plants Rheum emodi Wall., Phyllanthus amarus Linn., Eclipta alba Hassk., Andrographis paniculate Nees., and Picrorhiza kurroa Royle ex Benth., and optionally Fumaria officinalis, Tinospora cordifolia Miers., Terminalia chebula Retz., Cichorium intybus Linn., Tephrosea purpurea Linn. and Boerhaavia diffusa Linn. Excerpt(s): The present invention relates to a novel polyherbal composition, a process for the preparation of the composition, a method of treating Acute hepatitis due to Hepatitis E virus (HEV), Healthy hepatitis B virus carrier with a super infection (Intercurrent) by hepatitis E virus resulting in acute hepatitis therapeutic effects on hepatitis B virus infection e.g. acute hepatitis associated with Hepatitis B virus, Hepatitis B virus healthy carrier state, Hepadna viridae e.g. Duck hepatitis B virus and its use as a hepatoprotective agent. The present novel polyherbal hepatoprotective composition is derived essentially from four plants namely (1) Phyllanthus amarus Linn. (2) Eclipta alba Hassk (3) Andrographis paniculate Nees and (4) Picrorhiza kurroa Royle ex Benth. In addition, the present invention provides a novel effective treatment of acute Hepatitis E virus infection, healthy Hepatitis B carrier developing an acute hepatitis E virus infection, acute Hepatitis B and chronic Hepatitis B carrier state, and also as a hepatoprotective agent as well as an agent for improving the cell line functions. This composition comprises essentially extracts from plants namely (1) Rheum emodi Wall, (2) Phyllanthus amarus Linn, (3) Eclipta alba Hassk (4) Andrographis paniculate Nees and (5) Picrorhiza kurroa Royle ex Benth. The plant Phyllanthus amarus Linn is also referred to as Phyllanthus niruri Linn. Web site: http://www.delphion.com/details?pn=US06136316__
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Novel 1.alpha.,24-dihydroxycholecalciferol compositions, novel precursors thereof, and processes for preparing them Inventor(s): Hashimoto; Yoshinobu (Fujisawa, JA), Ikekawa; Nobuo (Tokyo, JA), Ishimoto; Sachio (Tokyo, JA), Kawashima; Hiroyuki (Hino, JA), Morisaki; Masuo (Tokyo, JA), Takeshita; Toru (Hino, JA) Assignee(s): Teijin Limited (osaka, Ja) Patent Number: 4,022,891 Date filed: June 2, 1975
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Abstract: Novel 1.alpha., 24-dihydroxycholecalciferol and derivatives thereof which are useful with reduced side-effects for the treatment of abnormal metabolism of calcium and phosphorus caused by liver failure, renal failure, gastrointestinal tract failure and parathyroid failure, and related bone diseases. Preparation of the novel 1.alpha., 24dihydroxycholecalciferol and their derivatives starts from 1.alpha., 24dihydroxycholesterol prepared by reacting 1.alpha., 2.alpha.-epoxy-24-keto-cholesta-4,6dien-3-one with an alkali metal and a proton donor in the presence of liquid ammonia or a liquid amine. Reaction of the 1.alpha., 24-dihydroxycholesterol with an allylic brominating agent, followed by contacting with a dehydrobrominating agent, affords 1.alpha.,3.beta., 24-trihydroxycholesta-5,7-diene derivative, which can then be converted to 1.alpha., 24-dihydroxycholocalciferol by ultraviolet irradiation in a organic solvent, followed by isomerization. Processes are also provided for separating 1.alpha., 24dihydroxycholesterol into an (S)-epimer and an (R)-epimer, and also for separating at least one of 1.alpha., 3.beta., 24(S)-and 1.alpha., 3.beta., 24(R)-trihydroxycholesta-5,7dienes from trihydroxycholesta-4,6-diene. Excerpt(s): This invention relates to novel 1.alpha., 24-dihydroxycholecalciferols, derivatives thereof, novel precursors thereof, and processes for preparing them. The invention also relates to a pharmaceutical composition for warm-blooded animals which comprises a pharmaceutically effective amount of the novel 1.alpha.,24dihydroxycholecalciferols, and a method for controlling the calcium metabolism of warm-blooded animals which comprises administering a pharmaceutically effective amount of the 1.alpha.,24-dihydroxycholecalciferol. The same representation as in the above formulae (5), (5-1) and (5-2) is used to express precursors of these compounds. Web site: http://www.delphion.com/details?pn=US04022891__
Patent Applications on Liver Failure As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to liver failure: •
Methods of treatment with selective EP4 receptor agonists Inventor(s): Cameron, Kimberly O.; (East Lyme, CT), Knight, Delvin R. JR.; (Ledyard, CT), Lefker, Bruce A.; (Gales Ferry, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030207925 Date filed: March 11, 2003 Abstract: The present invention provides a method of treating hypertension, liver failure, loss of patency of ductus arteriosus, glaucoma or ocular hypertension in a patient, comprising administering to the patient a therapeutically effective amount of a selective EP.sub.4 receptor agonist of Formula I 1or a prodrug thereof, a pharmaceutically acceptable salt of the selective EP.sub.4 receptor agonist or prodrug or
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This has been a common practice outside the United States prior to December 2000.
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a stereoisomer or diastereomeric mixture of the EP.sub.4 receptor agonist, prodrug or salt, wherein the variables X, Z, Q, and R.sup.2 are as defined in the specification. Excerpt(s): The present invention relates to methods for the treatment of disorders responsive to modulation of the prostaglandin E.sub.2 receptor, in a patient in need thereof, by administration of a receptor selective prostaglandin E.sub.2 agonist. More specifically, the present invention provides methods for the treatment of hypertension, liver failure, loss of patency of the ductus arteriosus, glaucoma or ocular hypertension in a patient in need thereof by administration of a selective prostaglandin E.sub.2 type 4 receptor agonist. The naturally occurring prostaglandins are comprised of several biological entities including prostaglandin E (PGE). Prostaglandin E.sub.2 (abbreviated as PGE.sub.2 herein) is known to be a cyclooxygenase induced oxidative metabolite in the arachidonic acid cascade, and it has been well documented that prostaglandins, including PGE.sub.2, have effects on many of the organs and systems of the body. For example, it is known that PGE.sub.2 has cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awakening effect, a sleep-inducing effect, a suppressive effect on gastric acid secretion, hypotensive activity and diuretic activity. In previous studies it has been found that the PGE.sub.2 receptor has various subtypes, each possessing differing physiological roles. At this time, it is known that the PGE.sub.2 receptor has four primary subtypes denoted EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4, each of which mediates different effects in various tissues and cells (Coleman, R. A. et al., Pharm. Rev. 1994, 46(2), 205-229). The EP.sub.4 receptor is distributed in such organs as the thymus, heart, kidney, liver, intestine, womb, ductus arteriosus and bone, and it is known that the EP.sub.4 receptor is related to relaxation of smooth muscle, differentiation and proliferation of lymphocytes, proliferation of mesangial cells, and collagen production of the fibroblasts. In both the pig and the dog, modulation of the EP.sub.4 receptor has been characterized with relaxation of the saphenous vein, and in the rabbit relaxation of the jugular vein occurs (Coleman, R. A. et al., Prostaglandins 1994, 47, 151). The EP.sub.4 receptor is also expressed in the ductus arteriosus (Bhattacharya, M. et al., Circulation 1999, 100, 17511756). The ductus arteriosus is an arterial connection in the fetus, which directs blood away from the pulmonary circulation and towards the placenta where oxygenation occurs (Heymann, M. A.; Rudolph, A. M. Physiol. Rev. 1975, 55, 62-78). In one proposed model the EP.sub.4 receptor in the ductus arteriosus acts as a sensor that responds to the perinatal drop in circulating levels of PGE.sub.2 by triggering closure of the ductus arteriosus (Nguyen, M. et al., Nature 1997, 390, 78-81). Closure of the ductus arteriosus was observed in an in vivo fetal sheep model after administration of a selective EP.sub.4 antagonist (PCT International Application WO 01/42281, published on Jun. 14, 2001). Maintaining the ductus arteriosus in the open, or patent state is desirable in the fetus and in infants with certain types of congenital heart defects where pulmonary or systemic blood flow depends on patency of the ductus arteriosus. Maintaining patency of the ductus arteriosus in infants with certain other types of congenital heart disease such as coarctation of the aorta, transposition of the great arteries, and Ebstein's anomaly may also be desirable. For example, infants with coarctation of the aorta, a condition constituting 7% to 8% of congenital cardiac defects, may have sudden onset of heart failure, cardiovascular collapse, and severe metabolic acidosis as the ductus arteriosus closes and distal perfusion is compromised. In cases such as these, PGE.sub.1 infusions have been utilized to reopen and maintain the patency of the ductus arteriosus prior to surgical repair of the defect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of selective EP4 receptor agonists for the treatment of liver failure, loss of patency of the ductus arteriosus, glaucoma or ocular hypertension Inventor(s): Cameron, Kimberly O.; (East Lyme, CT), Lefker, Bruce A.; (Gales Ferry, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030176479 Date filed: March 11, 2003 Abstract: The present invention is directed to methods for treating liver failure, loss of patency of the ductus arteriosus, glaucoma or ocular hypertension, comprising administering to the patient in need thereof a therapeutically effective amount of a selective EP.sub.4 receptor agonist of the Formulae 1wherein the variables A, B, Q,.dbd.U, and R.sup.2 for Formula l; and the variables Ar,.dbd.M,.dbd.N, R, W, and Z for Formula II are as defined in the specification. Excerpt(s): The present invention relates to methods of using receptor selective prostaglandin (PGE.sub.2) agonists for the treatment of liver failure, loss of patency of the ductus arteriosus, glaucoma or ocular hypertension in animals, particularly mammals. More specifically, the present invention relates to such methods using 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. Prostaglandin E.sub.2 (abbreviated as PGE.sub.2 herein) is known to be a cyclooxygenase induced oxidative metabolite in the arachidonic acid cascade, and it has been well documented that prostaglandins, including PGE.sub.2, have effects on many of the organs and systems of the body. For example, it is known that PGE.sub.2 has cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awakening effect, a sleep-inducing effect, a suppressive effect on gastric acid secretion, hypotensive activity and diuretic activity. In previous studies it has been found that the PGE.sub.2 receptor has various subtypes, each possessing differing physiological roles. At this time, it is known that the PGE.sub.2 receptor has four primary subtypes denoted EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4, respectively, each of which mediates different effects in various tissues and cells (Coleman, R. A. et al., Pharm. Rev. 1994, 46(2), 205229). The EP.sub.4 receptor is distributed in such organs as the thymus, heart, kidney, liver, intestine, womb, ductus arteriosus and bone, and it is known that the EP.sub.4 receptor is related to relaxation of smooth muscle, differentiation and proliferation of lymphocytes, proliferation of mesangial cells, and collagen production of the fibroblasts. In both the pig and the dog, modulation of the EP.sub.4 receptor has been characterized with relaxation of the saphenous vein, and in the rabbit relaxation of the jugular vein occurs (Coleman, R. A. et al., Prostaglandins 1994, 47, 151). Numerous studies have demonstrated the protective action of prostaglandin E.sub.1 on experimental models of liver injury and on patients with fulminant viral hepatitis, with PGE.sub.1 acting in many different ways to bring about this effect (Liu, X. L. et al. World J. Gastroenterol. 2000, 6(3), 326-329). For example, PGE.sub.1 could act upon the PGE.sub.1 receptor of diseased vessels to dilate them and increase portal venous flow, improve the microcirculation of the liver, clear the metabolites of the liver cells and increase oxygen supply to the liver tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with liver 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 “liver 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 liver failure. You can also use this procedure to view pending patent applications concerning liver 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 5. BOOKS ON LIVER FAILURE Overview This chapter provides bibliographic book references relating to liver failure. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on liver 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 “liver 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 liver failure: •
Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment Source: Malden, MA: Blackwell Science, Inc. 1999. 568 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]. Website: www.blackwellscience.com. PRICE: $125.00 plus shipping and handling. ISBN: 0632043423. Summary: Cirrhosis (liver scarring) is a very prevalent disease and ascites (fluid accumulation) is the most frequent complication. The development of ascites in cirrhosis is the consequence of the simultaneous occurrence of very complex processes leading to impairment in hepatic, circulatory, and renal function. The textbook offers 32 chapters on the pathogenesis, diagnosis and treatment of ascites and renal dysfunction in liver disease. Topics include historical notes on ascites in cirrhosis; characteristics of ascites;
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clinical disorders of renal function in cirrhosis with ascites; clinical disorders of renal function in acute liver failure; renal dysfunction and postoperative renal failure in obstructive jaundice; spontaneous bacterial peritonitis; the etiology, diagnosis, and management of noncirrhotic ascites; extracellular fluid volume homeostasis; physiology of the renal circulation; physiology of the gastrointestinal and liver circulation; the renin angiotensin aldosterone system in cirrhosis; the sympathetic nervous system in cirrhosis; arginine vasopressin in cirrhosis; atrial natriuretic peptide and other natriuretic factors in cirrhosis; arachidonic acid metabolites and the kidney in cirrhosis; nitric oxide and systemic and renal hemodynamic disturbances in cirrhosis; endothelin and systemic, renal, and hepatic hemodynamic disturbances in cirrhosis; the systemic circulation in cirrhosis; the splanchnic circulation in cirrhosis; alterations of hepatic and splanchnic microvascular exchange in cirrhosis (local factors in the formation of ascites); experimental models in the investigation of portal hypertension; renal dysfunction and ascites in carbon tetrachloride induced cirrhosis in rates; bacterial infection of the ascitic fluid in rates with carbon tetrachloride induced cirrhosis; the arterial vasodilation hypothesis of ascites formation in cirrhosis; prognosis of cirrhosis with ascites; the medical treatment of ascites in cirrhosis; treatment of ascites by paracentesis; the treatment of refractory ascites in cirrhosis; the treatment of hepatorenal syndrome in cirrhosis; drug induced renal failure in cirrhosis; liver transplantation in cirrhotic patients with ascites; and the treatment and prophylaxis of spontaneous bacterial peritonitis. Each chapter is written by experts in the field and includes extensive references. The text concludes with a subject index. •
Diseases of the Liver and Biliary System, Eleventh Edition Source: Malden, MA: Blackwell Science, Inc. 2002. 706 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: Designed to serve practicing physicians, surgeons and pathologists, as well as clinical students, this textbook presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The text offers 38 chapters: anatomy and function; the assessment of liver function; biopsy of the liver; the hematology of liver disease; ultrasound, computed tomography (CT scan) and magnetic resonance imaging (MRI); hepatocellular failure; hepatic encephalopathy; acute liver failure; ascites (fluid accumulation); the portal venous system and portal hypertension; the hepatic artery and hepatic vein, and the liver in circulatory failure; jaundice; cholestasis; primary biliary cirrhosis (PBC); sclerosing cholangitis; viral hepatitis, including general features, hepatitis A, hepatitis E, and other viruses; hepatitis B virus and hepatitis Delta virus; hepatitis C virus; chronic hepatitis, its general features and autoimmune chronic disease; drugs and the liver; hepatic cirrhosis (scarring); alcohol and the liver; iron overload states; Wilson's disease; nutritional and metabolic liver diseases; the liver in infancy and childhood; the liver in pregnancy; the liver is systemic disease, granulomas, and hepatic trauma; the liver in infections; nodules and benign liver lesions; malignant liver tumors; the role of interventional radiology and endoscopy in imaging of the biliary tract; cysts and congenital biliary abnormalities; gallstones and inflammatory gallbladder diseases; benign stricture of the bile ducts; diseases of the ampulla of Vater and the pancreas; tumors of the gallbladder and bile ducts; and hepatic transplantation. The text includes full-color and black-and-white illustrations and photographs. A detailed subject index concludes the volume.
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Gastroenterology and Hepatology: The Comprehensive Visual Reference. Volume 1: The Liver Source: Philadelphia, PA: Current Medicine. 1996. [200 p.]. Contact: Available from Current Medicine. 400 Market Street, Suite 700, Philadelphia, PA 19106. (800) 427-1796 or (215) 574-2266. Fax (215) 574-2270. E-mail:
[email protected]. Website: current-medicine.com. PRICE: $125.00 plus shipping and handling. ISBN: 1878132784. Summary: This atlas is one in an 8-volume collection of images that pictorially displays the gastrointestinal tract, liver, biliary tree, and pancreas in health and disease, both in children and adults. This volume includes 14 chapters on the liver. Several chapters deal with the major manifestations of liver disease, providing reviews of jaundice, portal hypertension, hepatic encephalopathy, ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis. The spectrum of manifestations of hepatitis (viral, autoimmune, and drug induced) is interwoven throughout the book. In addition, there is a comprehensive discussion of the problems attendant to the development of acute liver failure. The various causes of acute and chronic hepatitis are covered in depth and Hepatitis B and hepatitis C receive individual attention in separate chapters. The spectrum of drug-induced liver disease and the mechanisms by which drug-related liver injuries develop (and can be detected or prevented) is discussed. Liver disease caused by copper and iron receive special attention as do those disorders predominantly affecting the hepatic vasculature or the parnechyma in the form of abscesses or cysts. The volume describes tumors of the liver, once considered therapeutically hopeless, with emphasis on recently acquired information regarding the pathogenic roles of hepatitis B, hepatitis C, iron, and environmental toxins. The book includes a status report evaluating the roles of hepatic resection and transplantation as treatments for tumors. The last chapter of the book covers liver transplantation. The format of the atlas is visual images supported by relatively brief text. Tables, charts, diagrams, and photomicrographs are used extensively.
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Schiff's Diseases of the Liver. 8th ed Source: Hagerstown, MD: Lippincott Williams and Wilkins. 1999. 2 v., 1760 p. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 824-7390. PRICE: $229.00 plus shipping and handling. ISBN: 0397587694. Summary: This classic textbook on diseases of the liver emphases both the medical and surgical aspects of the diagnosis and management of liver diseases. Divided into 12 parts, the text covers general considerations, the consequences of liver disease, the cholestatic disorders, hepatitis, autoimmune liver disease, alcohol and drug induced diseases, genetic and metabolic diseases, vascular diseases and trauma, benign and malignant tumors, the liver in pregnancy and childhood, infectious and granulomatous disorders, and transplantation. In this 8th edition, the authors continue to chart the progress of scientific advances in the care of patients with liver disease. The authors identify and discuss the current challenges faced by investigators and clinicians, including the need for a vaccine to prevent hepatitis C; the development of ways to successfully support patients who have acute liver failure; the creation of effective, well tolerated treatments for chronic hepatitis B and C; and the development of genetically based tests to diagnose Wilson's disease, hemochromatosis, and the broad array of metabolic errors. Each chapter in the two volume set is written by experts in the field of hepatology and each is illustrated with figures, tables, and black and white
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photographs. Each chapter also contains extensive references. A section of color plates is included and a subject index is found at the end of each volume. •
Handbook of Liver Disease Source: Philadelphia, PA: Churchill-Livingstone. 1998. 534 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. Email:
[email protected]. PRICE: $73.00 plus shipping and handling. ISBN: 0443055203. Summary: This comprehensive handbook in outline format offers easy access to information on the full range of liver disorders, and covers symptoms, signs, differential diagnoses, and treatments. A total of 34 chapters cover the following topics: assessment of liver function and diagnostic studies, acute liver failure, chronic viral hepatitis, acute viral hepatitis, autoimmune hepatitis, alcoholic liver disease, fatty liver and nonalcoholic steatohepatitis, drug induced and toxic liver disease, cirrhosis and portal hypertension, portal hypertension and gastrointestinal bleeding, ascites and spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson's disease and related disorders, alpha 1 antitrypsin deficiency and other metabolic liver diseases, Budd Chiari syndrome and other vascular disorders, the liver in heart failure, the liver in pregnancy, the liver in systemic disease, pediatric liver disease, liver disease in the elderly, HIV and the liver, granulomatous liver disease, hepatic tumors, hepatic abscesses and cysts, other infections involving the liver, surgery in the patient with liver disease and postoperative jaundice, liver transplantation, cholelithiasis and cholecystitis, diseases of the bile ducts, and tumors of the biliary tract. The book features lists that summarize key information and numerous figures and tables on topics such as acetaminophen toxicity, classifications of chronic hepatitis, and indications for liver transplantation. Each chapter was written by an acknowledged expert in the field and includes references for additional study. A subject index concludes the volume.
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Living With Hepatitis C: Everything You Need to Know Contact: Firefly Books Incorporated, 4 Daybreak Ln, Westport, CT, 06880-2157, http://www.fireflybooks.com. Summary: This monograph explains the disease hepatitis C, its transmission, symptoms, prevention, and treatment. The monograph explains the different types of hepatitis, the function of the liver, the effect of hepatitis on the liver and on the health of the patient with hepatitis C, how hepatitis is diagnosed, drugs used for treatment, and their side effects. The monograph also discusses liver transplantation in the event of liver failure; the things a patient can do to promote good health, such as a healthy diet and avoiding smoking and alcohol; complementary therapies that are being tried and some that should be avoided; antiviral therapies and vaccines being researched; and how others can help the patient live with hepatitis C.
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Viral Hepatitis: Diagnosis, Treatment, Prevention Source: New York, NY: Marcel Dekker, Inc. 1997. 532 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. PRICE: $175.00. ISBN: 0824794168.
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Summary: This text familiarizes readers with current methods of diagnosis, treatment, and prevention of human viral hepatitis. Sixteen chapters cover: methods and applications of molecular diagnostic testing for viral hepatitis; the hepatitis A virus; the molecular biology and immunopathology of the hepatitis B virus; the prevention and therapy of clinical disease arising from the hepatitis B virus; the hepatitis C virus; the hepatitis D virus; the epidemiology and biology of the hepatitis E virus; other hepatitis viruses including the hepatitis G virus; the role of hepatitis viruses in acute liver failure; hepatocellular carcinoma and viral hepatitis; extrahepatic manifestations of chronic viral hepatitis; the overlap of chronic viral hepatitis and autoimmune hepatitis; liver transplantation and viral hepatitis B, D, and C; viral hepatitis in marrow and stem-cell transplant patients; viral hepatitis in the immunocompromised host; and the role of iron in chronic viral hepatitis. The authors evaluate diagnostic serological techniques such as ELISAs and PCRs; highlight nonhuman primate and transgenically created animal models used in disease transmission studies, virus isolation, and serological assays and vaccine development; review the management of fulminant hepatic failure and hepatitis in the immunocompromised patient; discuss how diagnosis may be complicated by predominant extrahepatic manifestations; assess various vaccines recent licensing and future prospects; and appraise the cost effectiveness of medical treatments with antiviral agents, the role of liver transplantation, and preventive measures. Each chapter includes extensive references, and a subject index concludes the volume. •
Oxford Textbook of Clinical Hepatology: Volume II Source: New York, NY: Oxford University Press. 1991. 825 p. Contact: Available from Oxford University Press. 200 Madison Avenue, New York, NY 10016. PRICE: $275 for 2-volume set. ISBN: 0192621564 (Volume 2); 0192619683 (2volume set). Summary: This textbook provides a comprehensive account of clinical hepatology. Volume II presents 65 chapters in 18 sections: immune disorders of the liver; alcoholic liver disease; non-alcoholic fatty liver; drug-induced liver; toxic liver injury; fulminant and subfulminant liver failure; inherited metabolic disorders; vascular abnormalities of hepatic and portal veins and hepatic arteries; tumors of the liver and bile duct; biliary tract diseases; the liver in diseases of other systems; the effect of liver disease on other systems; pediatric liver; liver in the elderly; hepatitis and HIV infection in homosexual men and injecting drug users; liver disease and pregnancy; the management of liver disease; and surgery, anesthesia, and the liver. The subject index for both volumes in appended. 6 appendices.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “liver failure” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “liver failure” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “liver failure” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):
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Acute Liver Failure by William M. Lee (Editor), Roger Williams (Editor); ISBN: 0521553814; http://www.amazon.com/exec/obidos/ASIN/0521553814/icongroupinterna
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Artificial organs : proceedings of a seminar on the clinical applications of membrane oxygenators and sorbent-based systems in kidney and liver failure and drug overdose, held at the University of Strathclyde, Glasgow, in August, 1976; ISBN: 0839109997; http://www.amazon.com/exec/obidos/ASIN/0839109997/icongroupinterna
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Encephalopathy and Nitrogen Metabolism in Liver Failure by International Symposium on Hepatic Encephalopathy and Nitrogen Metabol, et al; ISBN: 1402011571; http://www.amazon.com/exec/obidos/ASIN/1402011571/icongroupinterna
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Hepatic Encephalopathy in Chronic Liver Failure by Livio Capocaccia (Editor); ISBN: 0306417022; http://www.amazon.com/exec/obidos/ASIN/0306417022/icongroupinterna
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Hepatic support in acute liver failure; ISBN: 0398035393; http://www.amazon.com/exec/obidos/ASIN/0398035393/icongroupinterna
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Liver Failure (Clinics in Critical Care Medicine) by Roger Williams (Editor); ISBN: 0443031096; http://www.amazon.com/exec/obidos/ASIN/0443031096/icongroupinterna
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Potentially Reversible Model of Acute Liver Failure in the Pig: A Model to Test the Efficiency of a Bioartificial Liver (Acta Biomedica Lovaniensia, 240) by Inge Fourneau; ISBN: 9058671445; http://www.amazon.com/exec/obidos/ASIN/9058671445/icongroupinterna
Chapters on Liver Failure In order to find chapters that specifically relate to liver failure, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and liver 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 “liver failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on liver failure: •
Clinical Disorders of Renal Function in Acute Liver Failure Source: in Arroyo, V., et al, eds. Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. Malden, MA: Blackwell Science, Inc. 1999. p.6378. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781)-388-8250. Fax (781) 388-8270. E-mail:
[email protected]. Website: www.blackwellscience.com. PRICE: $125.00 plus shipping and handling. ISBN: 0632043423. Summary: Acute liver failure (ALF) is a core term that identifies a group of patients developing encephalopathy (abnormal function of the brain tissues) less than 12 weeks after the onset of jaundice, in the absence of underlying liver disease. These patients
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have important differences in clinical features and prognosis, depending on the etiology (cause), the time from the onset of jaundice to the development of encephalopathy, and the functional hepatic (liver) reserve. The development of renal (kidney) failure in such patients is commonplace. This chapter on clinical disorders of kidney function in ALF is from a textbook on ascites and renal dysfunction in liver disease. The key pathophysiologic features associated with the development of kidney failure are a decrease in kidney blood flow as a consequence of systemic hypotension (low blood pressure), and vasoconstriction within the kidney circulation. The causes of vasoconstriction are multifactorial, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and the development of endotoxemia with production of eicosanoids and free radicals. The chapter concludes with a discussion of renal function as a preoperative risk factor for early posttransplant mortality (death) and a review of treatment strategies for these disorders of kidney function in ALF. 3 figures. 1 table. 81 references. •
Approach to the Patient with Fulminant (Acute) Liver Failure Source: in Textbook of Gastroenterology. 4th ed. [2-volume set]. Hagerstown, MD: Lippincott Williams and Wilkins. 2003. p. 983-991. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-6423. Fax: (301) 223-2400. Website: www.lww.com. PRICE: $289.00. ISBN: 781728614. Summary: Fulminant (acute) liver failure (FLF) is a relatively uncommon condition characterized by hepatocyte necrosis (liver tissue death) and disruption of liver function in proportion to the degree of liver cell death. With extensive liver cell death comes the development of clinically obvious hepatic encephalopathy, which defines the clinical condition of FLF. This chapter on the approach to patients with FLF is from a lengthy, two-volume textbook that integrates the various demands of science, technology, expanding information, good judgment, and common sense into the diagnosis and management of gastrointestinal patients. The chapter first discusses the definition, pathogenesis, and etiology of FLF. Thereafter, the authors discuss the clinical management of these patients, divided into pre-intensive care unit (ICU) and ICU management of patients with FLF. Subsequently, liver transplantation and developments in transplantation are discussed, as well as the available bioreactors for use in patients with FLF. Supportive therapy allows both functional and structural regeneration of the liver after FLF, without the development of chronic liver disease. However, in certain cases, the prognosis is grave and is greatly improved by emergency liver transplantation. 2 tables. 58 references.
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CHAPTER 6. MULTIMEDIA ON LIVER FAILURE Overview In this chapter, we show you how to keep current on multimedia sources of information on liver failure. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on liver failure is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “liver failure” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “liver failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on liver failure: •
Talk, Talk, Talk Source: Washington, DC: Wendy Marx Foundation. 1994. (videocassette). Contact: Available from Wendy Marx Foundation. 322 South Carolina Avenue, SE, Washington, DC 20003. Fax (202) 546-0870. PRICE: Single copy free. Summary: Designed for a viewing audience of adolescents and young adults, this videotape program provides information about organ donation. The video opens with a series of vignettes about when teenagers are told not to talk: spending too much time on the telephone, during team meetings, or in class. Then the narrator, track and field star Carl Lewis, introduces the concept of organ donation, stressing the importance of talking about it with one's friends and family. The program reviews the basics of transplantation and the organs and tissues that are traditionally transplanted. Mr. Lewis outlines three basic concepts: everyone has to die; by thinking and planning ahead, one's death might save a life; and it is important to discuss one's wishes during good health, before the decision needs to be made. The program then introduces Wendy Marx, a
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young woman who experienced liver failure due to hepatitis B infection. Together Wendy and Carl describe the national network of organ donation and the people waiting for donor organs, how a single donor can help up to 25 people, the need to sign a donor card, and, most importantly, the need to talk about one's wishes. •
Hepatitis C: The Silent Scourge Source: Princeton, NJ: Films for the Humanities and Sciences. 1996. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail:
[email protected]. Website: www.films.com. PRICE: $99.00 plus shipping and handling. Order number CAF6419. Summary: Hepatitis C virus (HCV) is a disease that is transmitted primarily by contact with infected blood and that manifests few symptoms. As many as 3.5 million people in the United States are believed to carry the virus, and many are not even aware that they have been exposed; 10,000 die from it each year. This program, hosted by Drs. Miriam Alter and Harold Margolis of the Centers for Disease Control and Prevention (CDC), explains current knowledge about the newest strain of the hepatitis virus, and its causes, treatment, and prevention. The program is designed like a news report and begins with an overview of the role and functions of the liver. The program then reviews the various forms of the hepatitis virus, noting that all of them cause liver inflammation and cirrhosis and can lead to symptoms like the flu, dark urine, or jaundice (yellowing of the skin). The narrators review the ways each type is transmitted, the symptoms, the treatment and side effects, prognostic factors, the availability of immunization, and risk factors. The program goes into more depth on hepatitis C, interviewing patients and health care providers. A brief section describes the use of liver transplantation as the final option for end stage liver failure caused by hepatitis. Another section interviews Thelma King Theil, the chair of the Hepatitis Foundation International, who focuses on the activities of the organization, particularly those related to prevention.
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Hepatitis B: The Enemy Within Source: Princeton, NJ: Films for the Humanities and Sciences. 1996. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail:
[email protected]. Website: www.films.com. PRICE: $99.00 plus shipping and handling. Order number CAF6423. Summary: This program, featuring Dr. Harold Margolis and Dr. Frank Mahoney of the Centers for Disease Control and Prevention, explains current knowledge about hepatitis B, and its causes, treatment, and prevention. The program is designed like a news report and begins with an overview of the role and functions of the liver. The program then reviews the various forms of the hepatitis virus, noting that all forms cause liver inflammation and cirrhosis and can cause symptoms like the flu, dark urine, or jaundice (yellowing of the skin). The narrators then review how each type of hepatitis is transmitted, the symptoms, the treatment and side effects, prognostic factors, the availability of immunization, and risk factors for hepatitis A and C. The program then goes into more depth on hepatitis B, interviewing patients and health care providers. One young woman (age 26) who contracted hepatitis B at birth, describes her experiences with the disease and the psychosocial impact it has had on her life. The program discusses occupational risk factors, transmission, the geographic incidence and prevalence of hepatitis B, its typical course, and the problems associated with the
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development of chronic active hepatitis. A brief section describes the use of liver transplantation as the final option for end stage liver failure caused by hepatitis. The program then focuses on immunization programs, including those designed to vaccinate babies at birth, infants (during routine immunization), and adolescents. There is also some discussion about the difficulties of instituting successful vaccination programs for some high risk groups, including intravenous (IV) drug users and people with multiple sexual partners. •
Aging Brain Source: Sacramento, CA: Department of Aging. 1987. (videocassette, 6 handouts and 6 page training manual.). Contact: California Department of Aging, Training and Education Section. 1600 K Street, Sacramento, CA 95814. (916) 322-3110. PRICE: $10.00. Summary: This tape contains seven training segments designed for administrators and staff working in residential facilities for the aged. It reviews commonly held beliefs about aging that may negatively influence the care given to aging residents and how these myths developed. According to the tape, many believe that aged people are naturally "senile". Aged people can either accept this belief and act accordingly, creating a self-fulfilling prophecy in which they relinquish their independence to those caring for them, or they can rebel against their caregivers. Several studies related to aging are reviewed that suggest that there are only minor differences between the mental capacities of the young and aged. Treatable diseases that can affect the aged person's mental abilities are described including drug overdoses, malnutrition, dehydration, blood clots, brain tumors, depression, alcoholism, liver failure, kidney failure, drastic environmental changes, thyroid problems, heart failure, infections, diabetes, constipation, and emphysema. Organic brain syndromes, incurable diseases that affect mental capability, also are reviewed, including multi-infarct dementia, Pick's disease, Creutzfeldt-Jakob disease, Korsakoff's syndrome, Parkinson's disease, and Alzheimer's disease. Specific attention is given to changes in the brain that occur as the disease progresses, the symptoms, and possible risk factors and causes of the disease. Contact points for the Alzheimer's Association are provided for further information.
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Hepatitis 101: Basic Tools for Teaching Liver Wellness and Hepatitis Prevention Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording). Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail:
[email protected]. Website: www.hepfi.org. PRICE: $37.00; plus shipping and handling. Summary: This tutorial videotape was developed to help teachers, counselors, outreach workers, and health professionals offer effective and easy to communicate messages about liver wellness, and the prevention of viral hepatitis and substance abuse. Viral hepatitis is a disease caused by viruses that damage the liver. Serious cases can lead to life-threatening liver cirrhosis (or scarring), liver failure and eventually liver cancer. The most common forms of viral hepatitis include hepatitis A, hepatitis B and hepatitis C. This program focuses on hepatitis C and the risk factors that increase one's likelihood of contracting the disease, notably substance abuse. The program uses memorable analogies that everyone can relate to in their daily lives to motivate individuals to avoid liver damaging activities and to adopt healthier lifestyle behaviors.
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Viral Hepatitis and Blood Borne Pathogens: The Invisible Threat Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording). Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail:
[email protected]. Website: www.hepfi.org. PRICE: $45.00; plus shipping and handling. Summary: Viral hepatitis is a disease caused by viruses that damage the liver. Serious cases can lead to life-threatening liver cirrhosis (or scarring), liver failure and eventually liver cancer. The most common forms of viral hepatitis include hepatitis A, hepatitis B and hepatitis C. This program focuses on hepatitis B and C and the risk factors that increase one's likelihood of contracting the disease, notably substance abuse. The video is designed for an adult audience. Topics include prevention of hepatitis B and C, AIDS, substance abuse, cirrhosis, and transmission of hepatitis.
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CHAPTER 7. PERIODICALS AND NEWS ON LIVER FAILURE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover liver failure.
News Services and Press Releases One of the simplest ways of tracking press releases on liver 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 “liver 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 liver 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 “liver failure” (or synonyms). The following was recently listed in this archive for liver failure: •
Machine helps liver failure patients stay alive Source: Reuters Health eLine Date: June 20, 2003
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Bioreactor could bridge transplant waiting period for liver failure patients Source: Reuters Medical News Date: June 20, 2003
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Drug reactions replace viral infection as primary cause of acute liver failure Source: Reuters Industry Breifing Date: December 20, 2002
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Acetaminophen overdose leading liver failure cause Source: Reuters Health eLine Date: December 16, 2002
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Natural steroid prevents acetaminophen-induced liver failure in mice Source: Reuters Medical News Date: October 11, 2002
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Acetylcysteine for paracetamol overdose may cause misdiagnosis of liver failure Source: Reuters Medical News Date: October 11, 2002
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Diabetes increases the risk of acute liver failure Source: Reuters Medical News Date: July 12, 2002
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Treating celiac disease may reverse liver failure Source: Reuters Health eLine Date: April 24, 2002
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Partial transplant helps some with liver failure Source: Reuters Health eLine Date: November 13, 2001
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Transplantation of genetically modified hepatocytes may reverse liver failure Source: Reuters Medical News Date: August 22, 2001 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. 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
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Market Wire’s home page at http://www.marketwire.com/mw/home, type “liver 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 “liver failure” (or synonyms). If you know the name of a company that is relevant to liver failure, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “liver 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 “liver 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 liver 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
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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. •
Update on Intestinal Transplantation at Children's Hospital of Pittsburgh Source: APHS Newsletter. 6(3): 8. Fall-Winter 1994. Contact: Available from APHS. 158 Pleasant Street, North Andover, MA 01845-2797. (508) 685-4477. Fax (508) 685-4488. E-mail:
[email protected]. Summary: This brief article provides readers with an update on intestinal transplantation used at the Children's Hospital of Pittsburgh. The author introduces the primary surgeons and researchers involved in the intestinal transplantation program. The article describes the experience of 32 children who had the transplants. The article explains the use of the immunosuppressant FK 506; causes of intestinal failure that might indicate intestinal transplantation; total parenteral nutrition (TPN) and its complications; the number and nature of organs transplanted; TPN induced liver failure; combination liver and small intestine transplantation; postoperative considerations, including feeding and rejection; and problems with lymphoproliferative diseases post-transplantation. The article concludes with a brief discussion about followup.
Academic Periodicals covering Liver Failure Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to liver failure. In addition to these sources, you can search for articles covering liver 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 8. 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 liver failure. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).
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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 liver 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 “liver failure” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for
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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 liver failure: •
Bioartificial liver system utilizing xenogenic hep http://www.rarediseases.org/nord/search/nodd_full?code=1261
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N-acetylcysteine http://www.rarediseases.org/nord/search/nodd_full?code=1306
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Xenogeneic hepatocytes (trade name: HepatAssist Liver Assist System) http://www.rarediseases.org/nord/search/nodd_full?code=956
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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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/
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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.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “liver 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 12424 72 989 77 483 14045
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “liver failure” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Liver Failure In the following section, we will discuss databases and references which relate to the Genome Project and liver failure. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “liver failure” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for liver failure: •
Tubulopathy, Encephalopathy, and Liver Failure due to Complex Iii Deficiency Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606104 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “liver failure” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “liver failure” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on liver failure can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to liver 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 liver 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 “liver failure”:
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Cirrhosis http://www.nlm.nih.gov/medlineplus/cirrhosis.html Hepatitis B http://www.nlm.nih.gov/medlineplus/hepatitisb.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Liver Transplantation http://www.nlm.nih.gov/medlineplus/livertransplantation.html 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 liver failure. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Hepatitis B Source: Waco, TX: Health Edco. 1997. [4 p.]. Contact: Available from Health Edco. P.O. Box 21207, Waco, TX 76702-1207. (800) 2993366, ext. 295. Fax (817) 751-0221. PRICE: $0.90 each for 50 copies. Item number LE38088. Summary: Focusing on hepatitis B as a sexually transmitted disease, this brochure educates adolescents and young adults about the transmission and prevention of this illness. The brochure features color photographs of young adults, with bold graphics reminding readers to get tested by a health care provider. Hepatitis B has no symptoms in about half of all cases, but if symptoms are present, they can include muscle aches, joint pain, fever, fatigue, headache, dizziness, and loss of appetite. Consequently, hepatitis B symptoms are often mistaken for flu symptoms. Hepatitis B can be spread by sexual contact (oral, vaginal, or anal) with an infected person, from mother to baby during childbirth, or by puncturing the skin with a contaminated instrument (e.g., sharing intravenous drug needles or health care workers being exposed to needle sticks). The brochure emphasizes the importance of practicing abstinence, having only one sex partner, using condoms and nonoxynol 9 for each sexual encounter, and considering lifestyle issues in preventing the transmission of hepatitis B. Vaccines are available for persons at high risk. No satisfactory treatment presently exists for this type
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of hepatitis; postexposure vaccination may be recommended in some instances. The brochure concludes by discussing the consequences of hepatitis B infection, which can include development of chronic hepatitis or life threatening acute fulminant hepatitis, liver cancer or liver failure (from chronic liver infection), and monetary costs. The brochure concludes with the contact information for the Centers for Disease Control National Sexually Transmitted Diseases (STD) Hotline and the American Social Health Association's Hepatitis B Resource Center. •
Hepatitis C Prevention Source: Atlanta, GA: Centers for Disease Control and Prevention (CDC). 1998. [2 p.]. Contact: Available from Centers for Disease Control and Prevention (CDC). 1600 Clifton Road, NE, Hepatitis Branch, MS G-37 Atlanta, GA 30333. (888) 443-7232 or (888) 4HEPCDC. Fax (404) 371-5488. PRICE: Single copy free. Also available at www.cdc.gov/ncidod/diseases/hepatitis/ resource/hepcprev.htm. Summary: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of persons who have this disease. This brochure describes hepatitis C, explains how to prevent getting the disease, and outlines who should have a blood test to diagnose hepatitis C. Hepatitis C is serious for some persons, but not for others. Some people with liver damage due to hepatitis C may develop cirrhosis (scarring) of the liver and liver failure (which may take many years to develop). The brochure outlines recommendations to prevent the transmission of hepatitis C, noting that HCV is spread primarily by exposure to human blood. The brochure recommends that readers be tested for HCV if they received a blood transfusion or solid organ transplant before July 1992; they were treated with a blood product for clotting problems before 1987; they ever injected street drugs; they were ever on long term kidney dialysis; or they ever had a sexually transmitted disease (STD). Early diagnosis of hepatitis C is important so patients can be counseled about how to prevent transmission of HCV to others and so patients can be checked for liver disease and get treatment, if indicated. The brochure offers the web site and Hepatitis Hotline (888-443-7232) information of the Centers for Disease Control and Prevention (CDC).
•
Tyrosinemia Source: Cedar Grove, NJ: American Liver Foundation. 1997. 1 p. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) HEP-ABC. Fax (973) 256-3214. E-mail:
[email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Hereditary tyrosinemia is a genetic inborn error of metabolism associated with severe liver disease in infancy. This fact sheet from the American Liver Foundation (ALF) offers a brief overview of tyrosinemia. The disease is inherited in an autosomal recessive fashion which means that both parents must be carriers of the gene for the disease. There are two clinical appearances of tyrosinemia: the acute form, which features babies with poor weight gain, enlarged liver and spleen, distended abdomen, swelling of the legs, and increased tendency to bleeding, particularly nose bleeds. Despite vigorous therapy, death from liver failure frequently occurs between 3 and 9 months of age in these children. The more chronic form of tyrosinemia features a gradual onset and less severe clinical features; enlargement of the liver and spleen are prominent, the abdomen is distended with fluid, weight gain may be poor, and
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vomiting and diarrhea occur frequently. Affected patients usually develop cirrhosis (scarring of the liver) and its complications. Children with either type of tyrosinemia will require liver transplantation. Strict attention to excellent nutrition, adequate vitamin and mineral intake, prevents nutritional deterioration and helps keep the patient as well as possible for transplantation. Prenatal diagnosis is possible, which allows for genetic counseling and consideration of termination of pregnancy in affected infants. The fact sheet concludes with the contact information for ALF (800-GO-LIVER, www.liverfoundation.org ). •
Helpful Tips for Carriers of HBV Source: Silver Spring, MD: Hepatitis Foundation International. 200x. 1 p. Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904-2901. (800) 891-0707 or (301) 662-4200. Fax (301) 622-4702. E-mail:
[email protected]. Website: www.HepatitisFoundation.org. PRICE: $2.00 for 5 copies; bulk pricing available. Summary: Long term infection with the hepatitis B virus (HBV) affects over one million people in the United States. While a majority of infected people remain 'healthy carriers' for a lifetime and do not show ongoing liver damage, other carriers develop more severe liver disease, leading to cirrhosis (liver scarring), liver cancer, and liver failure. This fact sheet reviews helpful tips for carriers of HBV, both to care for themselves and to prevent the transmission of the infection to others. The tips cover topics including monitoring for complications, working with health care providers, preventing transmission, avoiding alcohol, and staying informed about research developments.
•
Hepatitis B and You. Pregnant? Protect Your Baby and Yourself Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1998. [4 p.]. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $0.89 each for 1-99 copies; plus shipping and handling; quantity discounts available. Order number: 31828A898. Summary: This brochure informs pregnant women about hepatitis B virus (HBV) and the risk of transmitting it to their baby. HBV attacks the liver and can cause chronic infection, cirrhosis (scarring) of the liver, liver cancer or liver failure, or even death. HBV can cause mild or severe flulike symptoms, and some people become carriers of chronic HBV infection. The brochure reviews how the disease is spread, most notably by contact with the body fluids (blood, semen, vaginal fluids) of people who are infected. HBV can also be transmitted from an infected mother to a baby at birth. Up to 90 percent of babies who are infected at birth become HBV carriers. The brochure then reviews preventive measures, encouraging readers to get tested (blood test) for the virus and explaining the actions to be taken based on a positive or negative test result. The brochure then explains the series of three vaccinations used to prevent HBV infection in babies. The brochure answers common questions about HBV and new mothers, including those about breastfeeding, financial aid programs, and other immunization recommendations. The Centers for Disease Control National Immunization Hotline telephone numbers are given (800-232-2522 for English; 800-232-0233 for Spanish). The brochure is written in nontechnical language and illustrated with full-color drawings of women and babies from various ethnic groups.
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Hepatitis C and You Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This brochure informs the general public about the hepatitis C virus (HCV). HCV is a virus that is in the blood that affects the liver causing liver failure, cancer, or even death. The early symptoms of HCV include fever, fatigue, nausea, vomiting, headache, stomachache, and loss of appetite; the later signs consist of dark-colored urine, light-colored stools, and yellowing of the skin and/or the eyes. Persons are at risk for HCV is they have ever shared needles for injection drug use, have jobs where they may come in contact with blood, have ever had a blood transfusion, or have shared personal items that might have had infected blood on them. HCV can also be passed through unprotected sex. It cannot be passed by shaking hands, hugging, or sitting next to a person who has HCV. Those persons that have HCV should follow their physicians' advice, rest, eat a healthy diet, and avoid drinking alcohol. To protect others from the virus, persons with HCV should not donate blood, avoid sharing personal items, cover all breaks in the skin, and notify their sexual partners. To prevent HCV, the readers should never share needles and should always practice safer sex with condoms. The brochure provides the phone number for the Substance Abuse Treatment's National Helpline.
•
Meet Oliver: The Liver Mascot for Viral Hepatitis Source: Jenkintown, PA: Hepatitis B Foundation. 1997. 2 p. Contact: Available from Hepatitis B Foundation. 101 Greenwood Avenue, Suite 570, Jenkintown, PA 19046. (215) 884-8786. Fax (215) 887-1931. E-mail:
[email protected]. Website: http://www.hebp.org. PRICE: Single copy free. Summary: This brochure introduces readers to the basic functions of the liver and to problems encountered with viral hepatitis (inflammation of the liver). The liver stores sugar and iron to help provide energy for the body; detoxifies compounds that have been eaten, drunk, breathed or absorbed through the skin; produces proteins for healthy growth; makes clotting factors for the blood; and works with the immune system to fight off infection. The three most common liver viruses are hepatitis A, B, and C. Although people can recover from an infection with these viruses, many become chronic carriers of hepatitis B and hepatitis C, which can lead to more serious complications later in life. Typical symptoms of viral hepatitis range from mild flu-like symptoms to fatigue, weakness, achiness, bloated stomach, and jaundice (yellow eyes and skin). Chronic hepatitis can result in cirrhosis, liver cancer, or liver failure. Certain behaviors and occupations may leave one at greater risk for contracting hepatitis. The brochure concludes with a brief list of recommendations for preventing viral hepatitis. The brochure is illustrated with a cartoon figure of a liver. The brochure includes the contact information for two nonprofit resource organizations: the Hepatitis B Foundation and the Hepatitis C Foundation. (AA-M).
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Heptitis B : 100 Times Easier to Catch Than HIV! Contact: Immunization Action Coalition, 1573 Selby Ave Ste 234, St Paul, MN, 55104, (651) 647-9009, http://www.immunize.org. Summary: This brochure, written for men who have sex with men (MSM), discusses the hepatitis B virus (HBV). Hepatitis B is a sexually transmitted liver disease, which is caused by HBV and can be fatal. Gay and bisexual men who have multiple partners are
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much more likely to acquire HBV than the general population. Individuals can protect themselves from HBV by getting the HBV vaccine and practicing safer sex with condoms and other barriers. HBV can be found in blood, semen, saliva, and vaginal secretions. It can be spread by unprotected anal or vaginal sex, needle-sharing for injection drug use, contact with open sores, the sharing of personal products such as toothbrushes and razors, human bites, and prolonged exposure to a person with HBV. The symptoms of hepatitis B include extreme tiredness, pain in joints, loss of appetite, nausea, fever, dark-colored urine, bloated and tender belly, yellowish tinged skin and eyes. Many adults who become infected will carry HBV for years or for life, are at increased risk for liver failure and liver cancer, and need ongoing medical care. An individual is diagnosed with HBV through a blood test. The HBV vaccine cannot protect individuals from the hepatitis A virus (HAV) or the hepatitis C virus (HCV). •
Hepatitis Basics Source: Kalamazoo, MI: Hope Publications. 200x. [4 p.]. Contact: Available from Hope Publications. 350 East Michigan Avenue, Suite 301, Kalamazoo, MI 49007-3851. (616) 343-0770. Website: hithope.com. PRICE: $0.59 each for 10-100 copies. Summary: This brochure, written in nontechnical language, offers a basic overview of human viral hepatitis, a disease that attacks the liver. The brochure describes the three main types: hepatitis A, hepatitis B, and hepatitis C. Hepatitis A infection is usually brief and causes no long term problems. However, hepatitis B and hepatitis C can lead to serious illness, including chronic (lifelong) infection, cirrhosis of the liver, liver cancer, liver failure, and death. The brochure emphasizes that the best way to deal with all three types of hepatitis is prevention. For each type, the brochure discusses risk factors, transmission, symptoms, and prevention strategies. Hepatitis A is transmitted through human feces, that is, in food or water that has been contaminated with feces. Raw foods such as fruits and vegetables pose the greatest risk (cooking kills the virus); but cooked foods can spread the disease if they're touched by contaminated hands after cooking. Hepatitis B is spread primarily through sexual contact, shared drug injection equipment contaminated by blood, infected blood on razors or needles (used for ear piercing, tattooing), and infected blood and body fluids (health care workers are at risk). It is also passed from infected mother to her baby at birth. Hepatitis C is most commonly spread shared drug injection equipment contaminated with blood. The brochure reiterates prevention steps for each type of hepatitis C, particularly those related to good hygiene (handwashing). One sidebar reminds readers who have had hepatitis B or C that they should not donate blood or organs, should not share toothbrushes or other personal care items, should cover open sores and other breaks in the skin, and should use a latex condom during sex. One final section offers further information about the hepatitis A vaccine and the hepatitis B vaccine.
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Chronic Hepatitis C: Current Disease Management Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse (NDDIC). 2001. 12 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (800) 891-5389 or (301) 6543810. Fax (301) 634-0716. E-mail:
[email protected]. Website: www.niddk.nih.gov. PRICE: Full-text available online at no charge; single copy free; bulk copies available. Order number: DD-172.
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Summary: This fact sheet educates readers about current patient care management strategies for people with chronic hepatitis C, which can cause cirrhosis, liver failure, and liver cancer. Approximately 20 percent of patients develop cirrhosis within ten to twenty years of the onset of infection. Liver failure resulting from chronic hepatitis C is one of the most common reasons for liver transplants in the U.S. Men, alcoholics, cirrhosis patients, people over age 40, and those infected for 20 to 40 years are more likely to develop HCV-related liver cancer. The fact sheet outlines the risk factors and transmission of hepatitis C virus (including sexual transmission, maternal-infant transmission, and sporadic transmission); and the clinical signs and symptoms, including those for cirrhosis and the extra-hepatic (nonliver) manifestations. The fact sheet also explains diagnostic tests used to confirm and monitor HCV infection, including enzyme immunoassays, recombinant immunoblot assays, PCR amplification, quantification of HCV RNA in serum, genotyping and serotyping of HCV, normal serum ALT levels, liver biopsy, and immunostaining; differentiating between acute and chronic hepatitis C; treatment options, notably the use of alpha interferon and patient selection issues; patient education; options for patients who do not respond to treatment; and the side effects of treatment. The fact sheet concludes with a discussion of present and future efforts in hepatitis C research. A brief description of the National Digestive Diseases Information Clearinghouse is provided on the back page, along with the contact information for two other sources of patient education materials. 5 figures. 9 references. •
Sexually Transmitted Diseases Contact: National Alliance of State and Territorial AIDS Directors, 444 N Capitol St NW Ste 339, Washington, DC, 20001-1512, (202) 434-8090, http://www.nastad.org. Summary: This fact sheet presents information about sexually transmitted diseases (STDs) and provides overviews of a variety of state and local prevention efforts. STDs are usually bacterial, viral, or fungal in origin and are generally curable. However, most viral STDs are usually incurable, and individuals with these infections must rely on suppression therapy. Anyone who is sexually active can contract an STD. Untreated STDs can cause a range of serious health problems including, cancer, liver failure, pelvic inflammatory disease (PID), sterility, and even death. STDs often occur as coinfections with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) because ulcers, lesions, or inflamed mucous membranes on the genitalia provide portals of entry into the bloodstream. STDs also cause a concentration of white blood cells, the principle host cells of HIV, in the infected area aiding in the development of HIV in the body. Safer sex education must include detailed information about STD prevention with regard to the full spectrum of human sexual activities. The fact sheet discusses eight efforts at the state and local levels to prevent the spread of STDs. These include funding to reduce barriers to treatment in Virginia; STD prevention in Wisconsin prisons; extensive surveillance in Oklahoma; outreach in bathhouses in Oregon; program integration plans in South Carolina; screening programs in Vermont; coordination and collaboration between HIV/AIDS, STD, and tuberculosis (TB) services in Washington; and HIV and STD services coordination in San Francisco.
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Hepatic Encephalopathy Source: Toronto, Ontario: Canadian Liver Foundation. 200x. 3 p. Contact: Available from Canadian Liver Foundation. Suite 1500, 2235 Sheppard Avenue East, Toronto Ontario, M2J 5B5. (416) 491-3353 or (800) 563-5483. Fax (416) 491-4952. E-
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mail:
[email protected]. Website:
[email protected]. PRICE: Full-text available online at no charge; Contact organization for print copies. Summary: This fact sheet, from the Canadian Liver Foundation, reviews hepatic encephalothy (HE), a disorder of mental activity, neuromuscular function, and consciousness that occurs as a result of either chronic or acute liver failure (ALF). This complex neuropsychiatric syndrome is primarily caused by metabolic abnormalities. Written in question-and-answer format, the fact sheet covers the normal function of the liver, cirrhosis (scarring) of the liver, the different types of HE, symptoms of the different stages of HE, diagnostic approaches to HE, the pathogenesis of HE, and treatment options. The author notes that the most important aspect of management of HE is the prompt recognition and correction of precipitating factors, when possible. These factors include kidney failure, use of sedatives or narcotics, gastrointestinal bleeding, hypokalemia or alkalosis, dietary protein increase, infection, constipation, and exacerbation of liver disease. The fact sheet concludes with the contact information for the Canadian Liver Foundation (www.liver.ca or 800-563-5483). •
About Hepatitis C Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1998. 15 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $0.89 each for 1-99 copies; plus shipping and handling; quantity discounts available. Order number: 20486A498. Summary: This health promotion booklet reviews hepatitis C, an infection of the liver. People infected with hepatitis C virus (HCV) may not show any symptoms or may develop flulike symptoms or jaundice. In most cases, people who become infected with HCV carry the virus for the rest of their lives. Carriers may show no signs of illness but can still pass HBV to others and are at higher risk of liver damage (such as cirrhosis), liver cancer, and death from liver failure. The brochure describes how HCV is spread by body fluids (blood, semen, vaginal fluids) through activities such as receiving a blood transfusion before 1992, having sex, sharing needles, or sharing personal items with a person who has HCV. Some health care workers may also be exposed to HCV at work. The brochure outlines the symptoms, encourages readers to be tested, and notes the care strategies that can be used by people who test positive for the virus. The brochure outlines strategies for preventing the spread of HCV, including having safer sex, cleaning drug works, not sharing personal items, and seeking treatment for HCV infection. The brochure lists the telephone numbers of resource organizations from which readers can get more information. The brochure is written in nontechnical language and illustrated with line drawings of cartoon-like figures.
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Keep Safe from Hepatitis B Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1998. 7 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $1.11 each for 1-99 copies; plus shipping and handling; quantity discounts available. Order number: 73066A698. Summary: This health promotion brochure reviews hepatitis B, an infection of the liver. People infected with hepatitis B virus (HBV) commonly develop flulike symptoms; most recover in about 6 months. In some cases, HBV causes a chronic infection that results in carrier status. Carriers usually stay infected for life, may show no signs of illness but can still pass HBV to others, and are at higher risk of liver damage (such as cirrhosis), liver
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cancer, and death from liver failure. The brochure describes how HBV is spread by body fluids (blood, semen, vaginal fluids) through activities such as having sex, sharing needles, or sharing personal items with a person who has HBV. Some health care workers may also be exposed to HBV at work, and pregnant women with HBV can pass the infection to their babies at birth. The brochure outlines the signs of HBV, encourages readers to be tested, and, if negative, emphasizes the importance of the hepatitis B vaccine. Three shots of the vaccine, spread over several months, are needed. The brochure outlines strategies for preventing the spread of HBV, such as having safer sex, cleaning drug works, not sharing personal items, and seeking treatment for chronic HBV infection. The brochure is written in nontechnical language and illustrated with full-color drawings of people from various ethnic groups. •
Could You Have Hepatitis C? Source: Cedar Grove, NJ: American Liver Foundation. 2002. [2 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) 4HEP-ABC. Fax (973) 256-3214. E-mail:
[email protected]. Website: www.liverfoundation.org. PRICE: $0.75 for single copy; bulk orders available; plus shipping and handling. Summary: This information card is designed to get basic information about hepatitis C distributed to the general public. The card stresses that the symptoms of hepatitis are often hidden until severe liver damage occurs, which is often too late for effective treatment. Some people experience flu-like symptoms, such as loss of appetite, nausea, vomiting, fever, weakness, fatigue, and mild abdominal pain. Untreated, chronic hepatitis can lead to scarring of the liver (cirrhosis), liver cancer, and liver failure. The reverse side of the care lists established risk factors and potential risk factors in a checkoff format. Readers are encouraged to get tested for hepatitis C if they have any of these risk factors. The card includes the contact information for the American Liver Foundation (ALF): www.liverfoundation.org or 1-888-4HEPUSA.
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Hepatitis C Prevention: Almost 4 Million Americans Have Been Infected With Hepatitis C Virus Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This pamphlet for the general public discusses the prevention and transmission of hepatitis C and who is at risk of having the disease. Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The infection is spread by contact with blood infected by the virus. Some persons carry hepatitis C and do not feel sick from the disease. Others with liver damage due to HCV may develop cirrhosis (scarring) of the liver and liver failure. To aid in the prevention of hepatitis C, the brochure suggests not shooting drugs; using clean syringes, water, and drug works if persons do shoot drugs; not sharing toothbrushes, razors, or other items that may have blood on them; using routine barrier precautions and safely handling needles and sharps if persons are health care workers; and considering the health risks associated with tattooing and body piercing. HCV can be spread by sex, but this does not occur often. Persons having sex with more than one partner can get other diseases, should use latex condoms, should be vaccinated against hepatitis B, and may want to consider abstinence from sex. HCV is not spread by breast feeding, casual contact, food or water, sneezing, coughing, or sharing eating utensils or drinking glasses. Many people who are at risk for hepatitis C
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are at risk for hepatitis A and B. Persons should ask their doctors for a blood test for HCV if they have ever injected street drugs, were treated for clotting problems with a blood product made before 1987, received a blood transfusion or solid organ transplant before July 1992, were notified that they received blood that possibly contained HCV, or were ever on long-term kidney dialysis. Early diagnosis is important so persons can be checked for liver disease, get treatment if indicated, learn how to protect their livers from further harm, and learn how they can prevent spreading HCV to others. •
If You Have Hepatitis C: Almost 4 Million Americans Have Been Infected With Hepatitis C Virus Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This pamphlet for the persons with hepatitis C provides information on the effects, treatment, transmission, and prevention of hepatitis C. Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is spread by contact with blood of persons infected with the virus. Some persons carry hepatitis C and do not feel sick from the disease. Others with liver damage due to HCV may develop cirrhosis (scarring) of the liver and liver failure. Persons who test positive for HCV should contact their doctors, as additional tests may be needed. Many persons with hepatitis C have no symptoms and feel well, but should still see their doctors. To take care of their livers, persons with HCV should see their doctors regularly, not drink alcohol, tell their doctor about all medicines they are taking, and be vaccinated against hepatitis A if there is liver damage. Drugs are licensed for the treatment of long-term hepatitis C. However, there is no vaccination against hepatitis C. Hepatitis C may have been acquired if persons injected street drugs, were treated for clotting problems with a blood product made before 1987, received a blood transfusion or solid organ transplant from an infected donor, were ever on long-term kidney dialysis, were health care workers and had frequent contact with blood in the work place, had mothers who had hepatitis C, had sex with a person infected with HCV, or lived with someone who was infected with HCV and shared items that might have had blood on them. To prevent the spread of HCV, persons with hepatitis C should not donate blood, body organs, other tissue, or sperm; should not share personal care articles that might have blood on them; should cover cuts and open sores; and may consider using barrier precautions during sex, although there is a low chance of transmitting HCV to a partner through sexual activity. About five out of every 100 infants born to women with HCV become infected; there is no preventable treatment. HCV is not spread by breast feeding, casual contact, food or water, sneezing, coughing, or sharing eating utensils or drinking glasses. Injection drug users should seek treatment, use clean drug works, and get vaccinated against hepatitis A and B. Persons having sex with more than one partner can get other diseases, should use latex condoms, should be vaccinated against hepatitis B, and may want to consider abstinence from sex.
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Could There Be A Hepatitis Carrier In This Family?: Is Liver Cancer In Their Future? Source: St. Paul, MN: Hepatitis B Coalition. 199x. 2 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. PRICE: $1 per copy. Summary: This patient education brochure reviews hepatitis B and how hepatitis B carrier status is related to an increased risk for developing liver failure or liver cancer. Topics include transmission of hepatitis B, symptoms, why hepatitis B is common
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among Asian people, the vaccine against hepatitis B, and the Hepatitis B Coalition of Minnesota. The brochure includes the mission statement of the Coalition and information about how to join the Coalition, including contact information. Ethnicallyappropriate line drawings illustrate the brochure. This brochure is also available in Hmong and Vietnamese. •
When You Have Hepatitis C Source: American Family Physician. 59(2): 357. January 15, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This patient education handout briefly reviews the recommendations for people who test positive for hepatitis C. A positive test for hepatitis C means that they are infected with the hepatitis C virus (HCV), an infection that causes a liver disease than can lead to liver failure. The handout notes that most people who get hepatitis C have the virus for the rest of their lives and end up with some liver damage. Some people don't feel sick from the liver damage for a long time and some get cirrhosis (liver scarring). The handout encourages readers to discuss the test results with their physician, noting that additional tests may be indicated to confirm the diagnosis and assess any liver damage. The handout also helps readers learn how to take care of the liver (to avoid additional damage), how to treat hepatitis C, how to avoid transmitting the virus to other people, and what are the risks that a mother can pass HCV to her baby at birth. Strategies to avoid transmission include refraining from donating blood, organs, tissue, or sperm; not sharing toothbrushes, razors, or other items that might have blood on them; keeping cuts and sores covered with bandages; and using condoms to lower the chance of transmission during sexual activity.
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Cirrhosis of the Liver Source: Bethesda, MD: American Gastroenterological Association. 199x. [4 p.]. Contact: American Gastroenterological Association (AGA). 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (800) 668-5237 or (301) 654-2055. Fax (301) 652-3890. Website: www.gastro.org. PRICE: Single copy free; bulk copies available. Summary: When chronic diseases cause the liver to become permanently injured and scarred, the condition is called cirrhosis. This brochure, from the American Gastroenterological Association (AGA), reviews the problem of cirrhosis. Topics include the major causes of cirrhosis, the symptoms of the condition, diagnostic methods used to confirm cirrhosis, treatment strategies, and treatment options for the complications of cirrhosis. Cirrhosis can result from direct injury to the liver cells (i.e., hepatitis), or from indirect injury via inflammation or obstruction to bile ducts (e.g., primary biliary cirrhosis, primary sclerosing cholangitis), which drain the liver cells of bile. Chronic alcoholism is the most common cause of cirrhosis in the United States. People with cirrhosis often have few symptoms at first. The two major problems that eventually cause symptoms are loss of functioning liver cells and distortion of the liver caused by scarring. Associated problems include fluid accumulation (ascites), jaundice (yellow skin), gallstones, intense itching, loss of appetite, fatigue and weakness, buildup of toxins, slowed drug processing, portal hypertension (high blood pressure in the main veins of the liver), and varices (thin walled, enlarged blood vessels). Diagnosis is confirmed from the patient's symptoms and from diagnostic tests such as CT scan, ultrasound, and biopsy. Treatment of cirrhosis is aimed to stop the development of scar tissue in the liver and prevent complications. Regardless of the cause of cirrhosis, every
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patient must avoid all substances, habits, and drugs that may further damage the liver, cause complications, or speed the progression to liver failure. Liver failure refers to the end stage of liver disease and cirrhosis when the liver stops working and cannot support life. The brochure includes a list of references and a diagram of the digestive tract, with organs labeled. 3 figures. 6 references. •
Liver Transplantation Source: idInsight. 2(3): 9. 1999. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (864) 241-0111. Fax (864) 244-2104. Website: www.irondisorders.org. Summary: When quality of life deteriorates because of advanced liver disease and the patient is not responding to therapies such as radiofrequency ablation, cryoablation, chemotherapy, and radiation, liver transplantation may be necessary to survive. This brief newsletter article, from the Iron Disorders Institute, reviews the use of liver transplantation. The author discusses preoperative care and testing, determining patient candidacy, the different types of liver transplantation (split liver, living related), and the signs of liver disease. Most donor livers come from cadavers; these livers must be recovered promptly and transplanted with 12 to 24 hours. Candidates for liver transplantation include patients with chronic liver disease such as cirrhosis, drug induced liver disease, Wilsons disease, hemochromatosis, acquired iron overload, some vascular diseases that contribute to liver failure, and primary liver cancer. The author notes that reducing the patient's iron levels with therapeutic phlebotomy (blood removal) can diminish the chances of developing liver cancer in those with cirrhosis of hemochromatosis. The article concludes with the contact number for the United Network for Organ Sharing (804-330-8500, www.unos.org) and two recommended websites for general information about liver surgery. The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “liver failure” (or synonyms). The following was recently posted: •
(1) Prevention and control of influenza. (2) Update: influenza activity-United States, 2003--04 season Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1984 April (revised 2003 Apr; addendum released 2003 Dec); Original guideline: 36 pages; addendum: 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4428&nbr=3342&a mp;string=liver+AND+failure
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(1) Prevention and treatment of tuberculosis among patients with infected human immunodeficiency virus: Principles of therapy and revised recommendations Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1998 October 30 (updated 2000 Mar); 59 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2157&nbr=1383&a mp;string=liver+AND+failure
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(1) Targeted tuberculin testing and treatment of latent tuberculosis infection Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 June 9 (addendum released 2003 August 8); 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4004&nbr=3134&a mp;string=liver+AND+failure
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2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology Source: American Society of Clinical Oncology - Medical Specialty Society; 1997 (revised 2001 Mar); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2746&nbr=1972&a mp;string=liver+AND+failure
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2002 national guideline on the management of sexually acquired reactive arthritis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3045&nbr=2271&a mp;string=liver+AND+failure
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2002 national guideline on the management of vulvovaginal candidiasis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3033&nbr=2259&a mp;string=liver+AND+failure
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2002 national guidelines on the management of early syphilis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3036&nbr=2262&a mp;string=liver+AND+failure
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A guideline for the management of heart failure Source: National Heart Foundation of New Zealand - Disease Specific Society; 1996 (revised 2001 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3309&nbr=2535&a mp;string=liver+AND+failure
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AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1997 (updated 2001 May-Jun); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2848&nbr=2074&a mp;string=liver+AND+failure
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ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Source: American College of Cardiology Foundation - Medical Specialty Society; 2000 (revised online 2002 Mar); 95 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3190&nbr=2416&a mp;string=liver+AND+failure
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ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperati Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 March 15 (revised 2002); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3149&nbr=2375&a mp;string=liver+AND+failure
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ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evalua Source: American College of Cardiology Foundation - Medical Specialty Society; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3114&nbr=2340&a mp;string=liver+AND+failure
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ACR Appropriateness Criteriatm for percutaneous catheter drainage of infected intraabdominal fluid collections Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2501&nbr=1727&a mp;string=liver+AND+failure
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ACR Appropriateness Criteriatm for solitary brain metastasis Source: American College of Radiology - Medical Specialty Society; 1999; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2503&nbr=1729&a mp;string=liver+AND+failure
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Acute pain management Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1997 (revised 1999 April 6); 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1888&nbr=1114&a mp;string=liver+AND+failure
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Altered nutritional status Source: American Medical Directors Association - Professional Association; 2001; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3304&nbr=2530&a mp;string=liver+AND+failure
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American Gastroenterological Association medical position statement: celiac sprue Source: American Gastroenterological Association - Medical Specialty Society; 2000 November 12 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3058&nbr=2284&a mp;string=liver+AND+failure
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American Gastroenterological Association medical position statement: guidelines for the evaluation and management of chronic diarrhea Source: American Gastroenterological Association - Medical Specialty Society; 1998 November 8 (reviewed 2001); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3065&nbr=2291&a mp;string=liver+AND+failure
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American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2002 November; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3491&nbr=2717&a mp;string=liver+AND+failure
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American Gastroenterological Association medical position statement: parenteral nutrition Source: American Gastroenterological Association - Medical Specialty Society; 2001 May 18; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3056&nbr=2282&a mp;string=liver+AND+failure
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American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation Source: American Gastroenterological Association - Medical Specialty Society; 2003 April; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3795&nbr=3021&a mp;string=liver+AND+failure
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Antithrombotic therapy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 March; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2907&nbr=2133&a mp;string=liver+AND+failure
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ASHP guidelines on preventing medication errors with antineoplastic agents Source: American Society of Health-System Pharmacists - Professional Association; 2002 September; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4312&nbr=3267&a mp;string=liver+AND+failure
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Assessment and management of acute pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2000 October (revised 2002 Oct); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3500&nbr=2726&a mp;string=liver+AND+failure
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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=liver+AND+failure
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Clinical practice guideline for the management of rheumatoid arthritis Source: Advanced Research Techniques in the Health Services - Private For Profit Research Organization; 2001; 170 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3683&nbr=2909&a mp;string=liver+AND+failure
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Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3170&nbr=2396&a mp;string=liver+AND+failure
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Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock Source: American College of Critical Care Medicine - Professional Association; 2002 June; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3433&nbr=2659&a mp;string=liver+AND+failure
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Community-acquired pneumonia in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1999 August (revised 2002 May); 41 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3351&nbr=2577&a mp;string=liver+AND+failure
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Congestive heart failure in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jan); 71 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3165&nbr=2391&a mp;string=liver+AND+failure
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Dehydration and fluid maintenance Source: American Medical Directors Association - Professional Association; 2001; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3305&nbr=2531&a mp;string=liver+AND+failure
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Diagnosis and management of epilepsy in adults. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2003 April; 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3737&nbr=2963&a mp;string=liver+AND+failure
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Diagnosis and management of foodborne illnesses: a primer for physicians Source: American Medical Association - Medical Specialty Society; Reprint released 2001 January; 88 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2707&nbr=1933&a mp;string=liver+AND+failure
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Diagnosis and treatment of adult degenerative joint disease (DJD) of the knee Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 June (revised 2002 May); 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3355&nbr=2581&a mp;string=liver+AND+failure
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Diagnosis and treatment of autoimmune hepatitis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2002 August; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3447&nbr=2673&a mp;string=liver+AND+failure
•
Diseases characterized by vaginal discharge. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3237&nbr=2463&a mp;string=liver+AND+failure
Patient Resources
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General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) Source: American Academy of Family Physicians - Medical Specialty Society; 2002 February 8; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3180&nbr=2406&a mp;string=liver+AND+failure
•
Global initiative for asthma. Global strategy for asthma management and prevention Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1995 January (revised 2002); 176 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3203&nbr=2429&a mp;string=liver+AND+failure
•
Guideline for diagnostic laparoscopy Source: Society of American Gastrointestinal Endoscopic Surgeons - Medical Specialty Society; 1998 April; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1861&nbr=1087&a mp;string=liver+AND+failure
•
Guidelines for quality standards for immunization Source: Infectious Diseases Society of America - Medical Specialty Society; 1997 (revised 2002); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3412&nbr=2638&a mp;string=liver+AND+failure
•
Guidelines for the management of leg ulcers in Ireland Source: Smith and Nephew, Ltd. - Private For Profit Organization; 2002; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3616&nbr=2842&a mp;string=liver+AND+failure
•
Guidelines for the use of antiretroviral agents in pediatric HIV infection Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 April (revised 2004 January 20); 79 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4619&nbr=3400&a mp;string=liver+AND+failure
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Hepatitis C. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3243&nbr=2469&a mp;string=liver+AND+failure
•
HIV disease management Source: University of Texas Medical Branch Correctional Managed Care - Academic Institution; 1996 September (revised 2002 Jul); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3477&nbr=2703&a mp;string=liver+AND+failure
•
Hyperglycemic crises in patients with diabetes mellitus Source: American Diabetes Association - Professional Association; 2000 October (revised 2001; republished 2003 Jan); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3582&nbr=2808&a mp;string=liver+AND+failure
•
Hypertension in older people. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2001 January; 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2915&nbr=2141&a mp;string=liver+AND+failure
•
Identifying and treating eating disorders Source: American Academy of Pediatrics - Medical Specialty Society; 2003 January; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3589&nbr=2815&a mp;string=liver+AND+failure
•
Immunizations Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 May (revised 2002 Jun); 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3353&nbr=2579&a mp;string=liver+AND+failure
•
Laboratory guidelines for screening, diagnosis, and monitoring of hepatic injury Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000; 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3520&nbr=2746&a mp;string=liver+AND+failure
Patient Resources
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Liver transplantation Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000 January; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3449&nbr=2675&a mp;string=liver+AND+failure
•
Management of chronic kidney disease and pre-ESRD in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 2000 November; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3099&nbr=2325&a mp;string=liver+AND+failure
•
Management of early rheumatoid arthritis. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 December; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2914&nbr=2140&a mp;string=liver+AND+failure
•
Management of hepatitis C: 2002 Source: National Institutes of Health (NIH) Consensus Development Panel on Management of Hepatitis C - Independent Expert Panel; 1997 March (revised 2002 August 26); 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3416&nbr=2642&a mp;string=liver+AND+failure
•
Management of primary biliary cirrhosis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000 April; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3445&nbr=2671&a mp;string=liver+AND+failure
•
Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=liver+AND+failure
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Massachusetts guidelines for adult diabetes care Source: Massachusetts Department of Public Health, Bureau of Family and Community Health, Diabetes Control Program - State/Local Government Agency [U.S.]; 1999 June (revised 2001 Jun); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3429&nbr=2655&a mp;string=liver+AND+failure
•
National High Blood Pressure Education Program: Working Group report on high blood pressure in pregnancy Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1990 (revised 2000 Jul); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1478&nbr=704&am p;string=liver+AND+failure
•
Palliative treatment of cancer Source: Finnish Medical Society Duodecim - Professional Association; 2001 December 27 (revised 2003 May 30); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4374&nbr=3296&a mp;string=liver+AND+failure
•
Physical activity in the prevention, treatment and rehabilitation of diseases Source: Finnish Medical Society Duodecim - Professional Association; 2002 May 7; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3398&nbr=2624&a mp;string=liver+AND+failure
•
Plague as a biological weapon. Medical and public health management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2000 October 4; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2983&nbr=2209&a mp;string=liver+AND+failure
•
Postexposure prophylaxis in children and adolescents for nonoccupational exposure to human immunodeficiency virus. Source: American Academy of Pediatrics - Medical Specialty Society; 2003 June; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3841&nbr=3057&a mp;string=liver+AND+failure
Patient Resources
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Practice guideline for the treatment of patients with bipolar disorder (revision) Source: American Psychiatric Association - Medical Specialty Society; 1994 December (revised 2002 Apr); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3302&nbr=2528&a mp;string=liver+AND+failure
•
Practice guidelines for the management of community-acquired pneumonia in adults Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 February; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2665&nbr=1891&a mp;string=liver+AND+failure
•
Practice guidelines for the treatment of tuberculosis Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 September; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2663&nbr=1889&a mp;string=liver+AND+failure
•
Practice parameters for the treatment of narcolepsy: an update for 2000. Source: American Academy of Sleep Medicine - Professional Association; 1994 (updated 2001 Jun); 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2933&nbr=2159&a mp;string=liver+AND+failure
•
Prevention and control of infections with hepatitis viruses in correctional settings Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 January 24; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3596&nbr=2822&a mp;string=liver+AND+failure
•
Prophylaxis of venous thromboembolism. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 October; 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3485&nbr=2711&a mp;string=liver+AND+failure
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Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1998 January 30 (revised 2003 November 26); 46 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4378&nbr=3300&a mp;string=liver+AND+failure
•
Recommendations for preventing transmission of infections among chronic hemodialysis patients Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2001 April; 46 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2789&nbr=2015&a mp;string=liver+AND+failure
•
Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update Source: American College of Rheumatology - Medical Specialty Society; 2000 September; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2935&nbr=2161&a mp;string=liver+AND+failure
•
Recommendations to prevent hepatitis B virus transmission-United States-Update Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 January 22; 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1982&nbr=1208&a mp;string=liver+AND+failure
•
Standards for breast conservation therapy in the management of invasive breast carcinoma. Source: American College of Radiology - Medical Specialty Society; 1992 (revised 2001); 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3291&nbr=2517&a mp;string=liver+AND+failure
•
Standards for the management of ductal carcinoma in situ of the breast (DCIS) Source: American College of Radiology - Medical Specialty Society; 1997 (revised 2001); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3292&nbr=2518&a mp;string=liver+AND+failure
Patient Resources
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The diagnosis and treatment of adult asthma Source: New Zealand Guidelines Group - Private Nonprofit Organization; 2002 September; 101 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3462&nbr=2688&a mp;string=liver+AND+failure
•
The management of diabetes mellitus in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 December; 147 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2583&nbr=1809&a mp;string=liver+AND+failure
•
Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Source: National Cholesterol Education Program - Federal Government Agency [U.S.]; 1993 September (updated 2001); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2969&nbr=2195&a mp;string=liver+AND+failure
•
Treatment of tuberculosis Source: American Thoracic Society - Medical Specialty Society; 2003 June 20; 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3829&nbr=3054&a mp;string=liver+AND+failure
•
Type 2 diabetes practice guidelines Source: International Diabetes Center - Private Nonprofit Organization; 2000 (revised 2001); 69 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2562&nbr=1788&a mp;string=liver+AND+failure
•
Ultrasonographic examinations: indications and preparation of the patient Source: Finnish Medical Society Duodecim - Professional Association; 2000 April 18 (revised 2001 October 24); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3385&nbr=2611&a mp;string=liver+AND+failure
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Vaccine preventable STDs. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3242&nbr=2468&a mp;string=liver+AND+failure
•
VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease. Source: Department of Defense - Federal Government Agency [U.S.]; 1999 August; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2584&nbr=1810&a mp;string=liver+AND+failure
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VHA/DoD clinical practice guideline for the management of dyslipidemia in primary care Source: Department of Defense - Federal Government Agency [U.S.]; 2001 December; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3187&nbr=2413&a mp;string=liver+AND+failure
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VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=liver+AND+failure
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VHA/DoD clinical practice guideline for the management of medically unexplained symptoms: chronic pain and fatigue Source: Department of Defense - Federal Government Agency [U.S.]; 2002 August; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3415&nbr=2641&a mp;string=liver+AND+failure
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VHA/DoD clinical practice guideline for the management of substance use disorders Source: Department of Defense - Federal Government Agency [U.S.]; 2001 September; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3169&nbr=2395&a mp;string=liver+AND+failure
Patient Resources
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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 liver 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to liver failure. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with liver 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 liver 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
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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 “liver 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 your search to “Organizations” and “liver 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 “liver 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 “liver failure” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.25
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
25
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 181 •
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
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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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
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 183 •
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/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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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/
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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
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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
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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LIVER FAILURE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] 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] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic 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]
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Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant 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] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] 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] Adverse Effect: An unwanted side effect of treatment. [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] 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] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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
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renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allo: A female hormone. [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] 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] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alprostadil: A potent vasodilator agent that increases peripheral blood flow. It inhibits platelet aggregation and has many other biological effects such as bronchodilation, mediation of inflammation, etc. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amanita: A genus of fungi of the family Agaricaceae, order Agaricales; most species are poisonous. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from
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which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] 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] Ammonium Chloride: An acidifying agent that is used as an expectorant and a diuretic. [NIH]
Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [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] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH]
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Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] 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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the
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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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
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] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating;
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inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [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] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [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] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Artificial Eye: Usually made of artificial plastic material or glass to which small quantities of metallic oxides have been added in order to imitate the features and coloring of the various
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parts of t he human eye; a prosthesis made of glass, plastic, or similar material. [NIH] Artificial Limbs: Prosthetic replacements for arms, legs, and parts therof. [NIH] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Ascitic Fluid: The serous fluid which accumulates in the peritoneal cavity in ascites. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] 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] Asterixis: A motor disturbance marked by intermittency of sustained contraction of groups of muscles. [NIH] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] 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] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH]
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Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] 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 Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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]
Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a
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diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [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] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]
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Blood Flow Velocity: A value equal to the total volume flow divided by the cross-sectional area of the vascular bed. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] 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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Neoplasms: Tumors or cancer of the breast. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH]
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Bupivacaine: A widely used local anesthetic agent. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [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] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH]
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Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalyse: To speed up a chemical reaction. [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [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]
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Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [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] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] 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] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH]
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Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [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] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholelithiasis: Presence or formation of gallstones. [NIH] Choleretic: A choleretic agent. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH]
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Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [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] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that
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yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the 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] 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] 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] 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. 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
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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 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] 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] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the
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anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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]
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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal
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replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] C-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]
Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [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
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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] Cytochrome-c Oxidase: An enzyme complex of the inner mitochondrial membrane that catalyzes the reaction between ferrocytochrome c and oxygen to yield ferricytochrome c and water. It is associated with the pumping of protons and the resultant phosphorylation of ADP to ATP. The reaction is the terminal event in the electron transport scheme by which oxygen is used for fuel combustion. EC 1.9.3.1. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [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] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes),
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bringing sequences, which are normally separated, into close proximity. [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] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] 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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [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] 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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]
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Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxycholecalciferols: Cholecalciferols substituted with two hydroxy groups in any position. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilate: Relax; expand. [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] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disaccharides: Sugars composed of two monosaccharides linked by glycoside bonds. [NIH] 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] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] 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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for
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its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [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] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductal carcinoma in situ: DCIS. Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called intraductal carcinoma. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [NIH] Duodenum: The first part of the small intestine. [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] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service
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produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU]
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Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [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] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [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] 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] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH]
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Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] 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] 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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH]
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Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Circulation: Diversion of blood flow through a circuit located outside the body but continuous with the bodily circulation. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [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] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical,
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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] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] 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 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] Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. [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
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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] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Foodborne Illness: An acute gastrointestinal infection caused by food that contains harmful bacteria. Symptoms include diarrhea, abdominal pain, fever, and chills. Also called food poisoning. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized
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connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [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] 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] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH]
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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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] 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]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [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]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH]
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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] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] 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] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] 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] Haemopoietic: Haematopoietic; pertaining to or effecting the formation of blood cells. [EU] Handwashing: The act of cleansing the hands with water or other liquid, with or without the inclusion of soap or other detergent, for the purpose of removing soil or microorganisms. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache,
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paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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] 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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] 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]
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Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatitis D: Hepatitis caused by the hepatitis delta virus in association with hepatitis B. It is endemic in some European countries and is seen in drug users, hemophiliacs, and polytransfused persons. [NIH] Hepatitis Delta Virus: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. Officially this is classified as a subviral satellite RNA. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [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] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]
Hepatoma: A liver tumor. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile
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nephrosis. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [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] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [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]
Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [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] Homotypic: Adhesion between neutrophils. [NIH] 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] Hospitals, Public: Hospitals controlled by various types of government, i.e., city, county, district, state or federal. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H,
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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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [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] Hypoglycemia: Abnormally low blood sugar [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness
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and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunization Programs: Organized services to administer immunization procedures in the prevention of various diseases. The programs are made available over a wide range of sites: schools, hospitals, public health agencies, voluntary health agencies, etc. They are administered to an equally wide range of population groups or on various administrative levels: community, municipal, state, national, international. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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]
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Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [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]
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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Information Systems: Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own
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psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [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-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH]
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Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [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] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intraductal carcinoma: Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called ductal carcinoma in situ. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [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] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU]
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Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [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 Transplantation: The transference of a kidney from one human or animal to another. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU]
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Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [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]
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Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Circulation: The circulation of blood through the vessels of the liver. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Enzyme Tests: Blood tests that look at how well the liver and biliary system are working. Also called liver function tests. [NIH] Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] 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
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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] 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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH]
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Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] 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]
Manic: Affected with mania. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] 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] 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 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] Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage. [NIH]
MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and
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store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercuric Chloride: Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesoderm: The middle germ layer of the embryo. [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] 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]
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Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] 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] 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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Morula: The early embryo at the developmental stage in which the blastomeres, resulting from repeated mitotic divisions of the fertilized ovum, form a compact mass. [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] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH]
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Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mushroom Poisoning: Poisoning from ingestion of mushrooms, primarily from, but not restricted to, toxic varieties. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] 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] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]
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Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel
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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] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [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] Nonoxynol: Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Nonoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide, formulated primarily as a component of vaginal foams and creams. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] 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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoprotein: Chromosomes consist largely of nuclei acids and proteins, joined here as
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complexes called nucleoproteins. [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] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [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] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [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] 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] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH]
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Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [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] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paracentesis: A procedure in which fluid is withdrawn from a body cavity via a trocar and cannula, needle, or other hollow instrument. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU]
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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] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [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] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic 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] Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH]
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Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] 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] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH]
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Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenprocoumon: 3-(1-Phenylpropyl)-4-hydroxycoumarin. Long acting oral anticoagulant. It may cause diarrhea. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] 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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] 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] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other
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nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] 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 Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] 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
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kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [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, 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] Postnatal: Occurring after birth, with reference to the newborn. [EU]
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Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] 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] Preceptorship: Practical experience in medical and health-related services that occurs as part of an educational program wherein the professionally-trained student works outside the academic environment under the supervision of an established professional in the particular field. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] 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] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside
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and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [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] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). 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
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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] Prostheses and Implants: Artificial substitutes for body parts, and materials inserted into tissue for functional, cosmetic, or therapeutic purposes. Prostheses can be functional, as in the case of artificial arms and legs, or cosmetic, as in the case of an artificial eye. Implants, all surgically inserted or grafted into the body, tend to be used therapeutically. Experimental implants is available for those used experimentally. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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 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 recurrent venous and arterial thrombosis. [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] 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] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V,
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VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] 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] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] 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] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [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]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are
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known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [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] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radionuclide scanning: A test that produces pictures (scans) of internal parts of the body. The person is given an injection or swallows a small amount of radioactive material; a machine called a scanner then measures the radioactivity in certain organs. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH]
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Raffinose: A trisaccharide occurring in Australian manna (from Eucalyptus spp, Myrtaceae) and in cottonseed meal. [NIH] Raltitrexed: An anticancer drug that inhibits tumor cells from multiplying by interfering with cells' ability to make DNA. Also called ICI D1694. [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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH]
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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] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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 Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [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] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Reproductive History: An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residential Facilities: Long-term care facilities which provide supervision and assistance in activities of daily living with medical and nursing services when required. [NIH] 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] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH]
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Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] 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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] 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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of 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] Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid
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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] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] 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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH]
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Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Education: Education which increases the knowledge of the functional, structural, and behavioral aspects of human reproduction. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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]
Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] 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] 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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
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Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]
Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU]
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Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Splanchnic Circulation: The circulation of blood through the vessels supplying the abdominal viscera. [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] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Steatosis: Fatty degeneration. [EU] Stellate: Star shaped. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
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] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Street Drugs: Drugs obtained and often manufactured illegally for the subjective effects they are said to produce. They are often distributed in urban areas, but are also available in
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suburban and rural areas, and tend to be grossly impure and may cause unexpected toxicity. [NIH]
Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] 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] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] 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] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [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] Superinfection: A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. Experimental challenge and in vitro models are sometimes used in virulence and infectivity studies. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH]
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Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [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] 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] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Tegafur: 5-Fluoro-1-(tetrahydro-2-furanyl)-2,4-(1H,3H)-pyrimidinedione. Congener of fluorouracil with comparable antineoplastic action. It has been suggested especially for the treatment of breast neoplasms. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [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] 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
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is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] 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] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH]
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Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] 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] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] 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] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Track and Field: Sports performed on a track, field, or arena and including running events and other competitions, such as the pole vault, shot put, etc. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]
Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH]
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Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Trifluoperazine: A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [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] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [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] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]
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Tuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be 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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
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,
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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]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [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] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginal Discharge: A common gynecologic disorder characterized by an abnormal, nonbloody discharge from the genital tract. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Varicella: Chicken pox. [EU] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] 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]
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VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Viremia: The presence of viruses in the blood. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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
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together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voluntary Health Agencies: Non-profit organizations concerned with various aspects of health, e.g., education, promotion, treatment, services, etc. [NIH] Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [NIH] Voriconazole: A drug that treats infections caused by fungi. [NIH] Waiting Lists: Prospective patient listings for appointments. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [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] 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] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by
Dictionary 267
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]
269
INDEX 3 3-dimensional, 20, 51, 187 A Abdomen, 153, 187, 197, 213, 226, 229, 230, 239, 240, 241, 242, 257, 260 Abdominal, 54, 96, 159, 165, 187, 199, 216, 227, 231, 233, 240, 242, 257, 263 Abdominal Pain, 159, 187, 216, 231, 242, 263 Ablation, 40, 187 Acceptor, 187, 230, 240, 260, 261 Acetaminophen, 4, 7, 10, 31, 34, 35, 40, 52, 71, 77, 101, 102, 110, 124, 134, 187, 216 Acetone, 187, 228 Acetylcholine, 187, 201, 238 Acetylcysteine, 7, 110, 134, 139, 187 Acidosis, 63, 89, 98, 117, 187 Actin, 187, 217 Activities of Daily Living, 187, 252 Acute lymphoblastic leukemia, 92, 187 Acute lymphocytic leukemia, 187 Acute renal, 4, 6, 96, 187, 220 Acyl, 39, 188 Adaptability, 188, 200 Adaptation, 53, 188, 201, 244 Adenocarcinoma, 188, 221 Adenosine, 188, 243 Adipose Tissue, 41, 188 Adjustment, 188 Adrenal Cortex, 188, 189, 205, 206, 247 Adrenal Glands, 188, 190 Adverse Effect, 56, 103, 135, 188, 210, 228, 243, 255 Affinity, 188, 194, 256 Age of Onset, 188, 263 Agonist, 116, 117, 118, 188, 210 Albumin, 6, 19, 48, 73, 82, 88, 188, 239, 244 Aldosterone, 122, 127, 189 Algorithms, 189, 196 Alimentary, 3, 5, 98, 99, 189, 240, 241 Alkaline, 187, 189, 190, 198, 259 Alkaloid, 189, 203 Alkalosis, 158, 189, 259 Alleles, 23, 189 Allo, 27, 189 Allograft, 102, 189 Allylamine, 189 Alpha Particles, 189, 250
Alpha-1, 23, 189 Alpha-fetoprotein, 65, 189, 215 Alprostadil, 65, 189 Alternative medicine, 134, 189 Alveoli, 189, 249 Amanita, 4, 189 Amine, 116, 189 Amino Acid Sequence, 190, 191, 217 Ammonia, 13, 16, 26, 57, 64, 66, 70, 71, 83, 116, 189, 190, 218, 223, 263 Ammonium Chloride, 16, 190 Amphetamines, 190, 203 Amplification, 157, 190 Ampulla, 122, 190, 201, 212 Amyloidosis, 67, 85, 96, 190 Anaesthesia, 190, 225 Anal, 47, 152, 156, 190, 230 Analgesic, 35, 187, 190, 208, 223 Analog, 190, 216, 229 Analogous, 190, 210, 262 Anaphylatoxins, 190, 204 Anatomical, 190, 194, 201, 205, 209, 224, 234, 254 Androgens, 188, 190, 205 Anemia, 92, 149, 190, 232 Anesthesia, 6, 125, 191, 237, 247 Aneurysm, 191, 264 Angina, 164, 191 Angiogenesis, 28, 191, 232 Angiotensinogen, 191, 252 Animal model, 12, 14, 15, 20, 28, 29, 33, 35, 42, 53, 125, 191, 263 Anions, 188, 191, 227 Annealing, 191, 245 Antibacterial, 191, 228, 256 Antibiotic, 191, 202, 213, 241, 256, 262 Antibodies, 22, 29, 67, 72, 191, 192, 194, 213, 224, 231, 235, 244 Antibody, 30, 43, 188, 191, 192, 203, 204, 222, 223, 224, 225, 227, 228, 232, 235, 250, 256, 266 Anticoagulant, 191, 243, 248, 249 Anticonvulsant, 191, 198, 243 Antidepressant, 5, 191 Antidiuretic, 63, 191 Antidote, 110, 191, 215 Antiemetic, 191, 192, 201, 262 Antifungal, 191, 228
270
Liver Failure
Antigen, 12, 14, 65, 188, 191, 192, 203, 208, 213, 222, 223, 224, 225, 232, 234, 247 Antigen-Antibody Complex, 192, 203 Antigen-presenting cell, 192, 208 Anti-infective, 192, 223 Anti-inflammatory, 187, 192, 194, 206, 208, 218, 223, 246 Anti-Inflammatory Agents, 192, 194, 206 Antimetabolite, 192, 216, 253 Antineoplastic, 166, 192, 206, 216, 259, 265 Antineoplastic Agents, 166, 192, 206, 265 Antioxidant, 44, 192, 240 Antipsychotic, 192, 201, 237, 262 Antipyretic, 35, 187, 192, 208 Antiseptic, 187, 192, 199, 233 Antiserum, 44, 192 Antiviral, 15, 20, 21, 28, 29, 37, 41, 48, 110, 124, 125, 187, 192, 226, 253 Antiviral Agents, 21, 125, 192 Anuria, 193, 228 Anus, 190, 193, 197, 203 Anxiety, 11, 193, 228 Aorta, 117, 193, 199, 210, 265 Apathy, 193, 237 Aplastic anemia, 84, 193 Apoptosis, 27, 28, 31, 33, 36, 44, 52, 193, 199 Approximate, 40, 193 Aqueous, 193, 195, 207, 223 Arachidonate 15-Lipoxygenase, 193, 230 Arachidonate Lipoxygenases, 193, 230 Arachidonic Acid, 117, 118, 122, 193, 211, 229, 247, 248 Arginine, 122, 190, 193, 238, 262 Arrhythmia, 94, 193 Arterial, 13, 66, 72, 96, 106, 117, 122, 189, 193, 199, 223, 229, 248, 259 Arteries, 117, 125, 193, 197, 199, 202, 205, 231, 234, 236, 244, 260 Arterioles, 193, 197, 198, 234, 264 Arteriosus, 117, 118, 193, 249 Arteriovenous, 193, 234 Artery, 106, 191, 193, 205, 211, 249, 252, 254 Articular, 193, 239 Artificial Eye, 193, 194, 248 Artificial Limbs, 194 Artificial Organs, 27, 62, 81, 95, 99, 100, 101, 194 Ascitic Fluid, 122, 194 Aseptic, 194, 239, 257 Aspirin, 40, 194
Assay, 46, 53, 62, 194 Asterixis, 26, 194 Astringent, 194, 199 Astrocytes, 35, 57, 194, 234 Asymptomatic, 54, 194, 221, 240 Ataxia, 148, 149, 194, 260 Atrial, 122, 194 Atrium, 194, 265 Atrophy, 78, 148, 194 Attenuation, 40, 194 Autoantibodies, 54, 194 Autoantigens, 194 Autodigestion, 194, 240 Autoimmune disease, 22, 54, 195, 235, 244 Autoimmune Hepatitis, 81, 94, 124, 125, 168, 195 Autologous, 30, 195 Autonomic, 187, 192, 195, 238, 242, 259 Autonomic Nervous System, 195, 242, 259 Autopsy, 92, 195 B Bacillus, 195, 262 Bacterial Infections, 4, 195, 200 Bacterial Physiology, 188, 195 Bactericidal, 195, 213 Bacteriophage, 195, 262 Bacterium, 195, 204, 220 Basal Ganglia, 26, 192, 194, 195, 217 Basal Ganglia Diseases, 194, 195 Base, 30, 189, 195, 208, 217, 228, 259, 263 Basement Membrane, 195, 199, 214, 229 Benign, 122, 123, 195, 217, 219, 237, 250 Benzodiazepines, 195, 215 Bile Acids, 6, 64, 99, 196, 257, 259 Bile Acids and Salts, 196 Bile duct, 22, 33, 54, 122, 124, 125, 161, 196, 201, 216, 246 Bile Pigments, 196, 228 Biliary, 22, 33, 48, 54, 122, 123, 124, 125, 196, 201, 230, 240 Biliary Tract, 122, 124, 125, 196, 240 Bilirubin, 6, 16, 63, 64, 188, 196, 216, 223 Biochemical, 15, 21, 26, 30, 43, 49, 72, 82, 189, 192, 196, 197, 215, 228, 229, 239, 255 Biological response modifier, 196, 226 Biological therapy, 196, 219 Biopsy, 31, 58, 122, 157, 161, 196, 242 Bioreactors, 127, 196 Biotechnology, 59, 134, 145, 147, 148, 149, 196 Bipolar Disorder, 173, 196 Bladder, 196, 204, 235, 248, 264
Index 271
Blastocyst, 114, 196, 204, 244, 262 Blood Coagulation, 196, 197, 198, 215, 260 Blood Flow Velocity, 66, 197 Blood Glucose, 4, 197, 220, 226 Blood Platelets, 197, 232, 255, 260 Blood pressure, 127, 161, 172, 197, 223, 235, 245, 256 Blood transfusion, 9, 153, 155, 158, 160, 197 Blot, 24, 197 Body Fluids, 154, 156, 158, 159, 189, 197, 198, 210, 256, 263 Bone Marrow, 17, 38, 48, 80, 98, 187, 193, 197, 217, 224, 231, 232, 235, 256, 258 Bone Marrow Cells, 98, 197, 232 Bowel, 54, 190, 197, 209, 212, 226, 242, 255, 257, 263 Bowel Movement, 197, 209, 257 Brachytherapy, 197, 226, 227, 250, 266 Bradykinin, 197, 238, 244 Branch, 153, 170, 183, 197, 211, 221, 231, 241, 249, 256, 260 Breakdown, 197, 208, 217 Breast Neoplasms, 197, 259 Bronchioles, 189, 197, 249 Bronchitis, 197, 202 Bronchoalveolar Lavage, 49, 197 Bronchoalveolar Lavage Fluid, 49, 197 Bupivacaine, 198, 229 Bypass, 97, 198 C Calcium, 116, 198, 203, 217, 232, 240, 248, 255, 259 Callus, 198, 211, 239 Candidiasis, 163, 198 Candidosis, 198 Cannula, 198, 240 Capillary, 197, 198, 245, 265 Capsid, 24, 198, 265 Carbamazepine, 60, 198 Carbohydrate, 65, 198, 205, 219, 245 Carbon Dioxide, 198, 217, 244, 252 Carcinoembryonic Antigen, 65, 198 Carcinogenesis, 46, 198 Carcinogenic, 198, 225, 239, 247, 257, 263 Carcinogens, 198, 236, 239, 266 Carcinoma, 15, 60, 109, 164, 174, 198, 199, 206 Carcinoma in Situ, 199 Cardiac, 19, 25, 117, 189, 199, 207, 211, 213, 220, 229, 236, 253, 257, 258 Cardiomyopathy, 39, 63, 199
Cardiorespiratory, 19, 199 Cardiovascular, 117, 164, 199, 229, 255 Carrier Proteins, 199, 244 Carrier State, 115, 199 Case report, 18, 67, 96, 199, 202, 214 Case series, 5, 199, 202 Caspase, 36, 59, 65, 199 Catalyse, 199, 261 Catechol, 36, 199 Catecholamine, 199, 209, 242 Catheter, 165, 199 Causal, 7, 199 Causality, 39, 199 Cause of Death, 4, 13, 16, 17, 33, 47, 199 Celiac Artery, 199, 221 Celiac Disease, 134, 199 Cell, 7, 10, 12, 13, 14, 15, 16, 17, 23, 25, 26, 27, 28, 30, 32, 33, 34, 35, 36, 37, 38, 41, 44, 45, 48, 49, 50, 51, 53, 55, 57, 66, 75, 77, 79, 80, 82, 83, 86, 102, 114, 115, 125, 127, 148, 149, 187, 188, 189, 190, 192, 193, 194, 195, 196, 199, 200, 201, 202, 204, 206, 207, 208, 211, 212, 214, 215, 216, 217, 218, 219, 221, 224, 225, 226, 227, 228, 229, 232, 234, 235, 237, 238, 239, 240, 243, 244, 247, 251, 252, 254, 255, 257, 258, 260, 261, 262, 263, 265, 266 Cell Count, 49, 55, 200 Cell Death, 28, 30, 38, 44, 127, 193, 200 Cell Differentiation, 200, 255, 257 Cell Division, 148, 195, 200, 219, 234, 244, 254 Cell Lineage, 48, 200 Cell membrane, 199, 200, 208, 217, 243 Cell motility, 200, 221 Cell proliferation, 17, 33, 45, 200, 255 Cell Size, 200, 215 Cell Survival, 35, 36, 200, 219 Cell Transplantation, 13, 29, 34, 45, 49, 82, 200 Cellulose, 200, 216, 244 Central Nervous System Infections, 200, 219 Cerebellar, 194, 200, 251 Cerebral Cortex, 194, 200, 213, 214 Cerebrospinal, 200, 255 Cerebrospinal fluid, 200, 255 Cerebrum, 200, 259, 263 Character, 201, 207, 218 Chemokines, 44, 201 Chemotactic Factors, 201, 204, 238 Chemotherapy, 74, 98, 102, 162, 167, 201
272
Liver Failure
Chenodeoxycholic Acid, 201, 264 Chin, 201, 233 Chlorpromazine, 201, 262 Cholangitis, 12, 43, 54, 122, 201 Cholecystitis, 124, 201 Cholelithiasis, 124, 201 Choleretic, 201, 264 Cholestasis, 31, 52, 67, 96, 122, 201 Cholesterol, 108, 175, 196, 201, 210, 216, 223, 230, 231, 257 Choline, 26, 201 Chromatin, 37, 193, 201 Chromosomal, 190, 201, 254 Chromosome, 17, 201, 204, 219, 254 Chronic Disease, 122, 161, 201 Chronic lymphocytic leukemia, 79, 201 Chronic Obstructive Pulmonary Disease, 176, 202 Chronic renal, 135, 202, 245, 263 Ciliary, 193, 202 Ciliary Arteries, 193, 202 Ciliary Body, 193, 202 Circulatory system, 202, 227 Cisplatin, 98, 202 C-kit receptor, 202, 257 Clarithromycin, 76, 202 Clinical study, 202, 205 Clinical trial, 7, 24, 26, 28, 30, 43, 48, 54, 68, 109, 110, 145, 202, 205, 241, 249, 251 Clone, 21, 22, 202 Cloning, 196, 202 Coagulation, 63, 68, 95, 196, 202, 221, 244, 260 Coca, 202, 203 Cocaine, 17, 203 Coculture, 98, 203 Cofactor, 203, 248, 260 Cognition, 203, 237 Colitis, 43, 203 Collagen, 33, 117, 118, 190, 195, 203, 214, 215, 232, 244, 247 Collapse, 57, 117, 197, 203 Colloidal, 188, 203 Colon, 43, 148, 198, 203, 229, 263 Colorectal, 107, 163, 203 Colorectal Cancer, 163, 203 Complement, 31, 95, 190, 203, 204, 218, 244 Complement Activation, 95, 190, 204 Compliance, 11, 204 Computational Biology, 145, 147, 204 Computed tomography, 122, 204, 254
Computer Simulation, 19, 204 Computerized tomography, 204 Conception, 204, 215, 257 Concomitant, 16, 204 Condoms, 152, 155, 156, 159, 160, 161, 204 Conduction, 204, 237 Congestion, 10, 192, 204 Conjugated, 196, 201, 204, 206 Conjugation, 78, 204 Conjunctiva, 202, 204, 225 Connective Tissue, 197, 203, 205, 215, 217, 231, 253, 258 Connexins, 205, 217 Consciousness, 158, 190, 205, 208, 221, 253 Constipation, 131, 158, 192, 205, 242 Constriction, 205, 227, 249, 254, 264 Constriction, Pathologic, 205, 264 Consumption, 19, 205, 239, 240 Contamination, 205, 221, 222 Contractility, 50, 205 Contraindications, ii, 205 Control group, 56, 205 Controlled clinical trial, 6, 205 Controlled study, 69, 205 Coordination, 157, 205, 235 Cornea, 205, 267 Coronary, 205, 234, 236 Coronary Thrombosis, 205, 234, 236 Cortical, 205, 254, 260 Corticosteroid, 86, 205, 246 Cortisol, 188, 206 Cortisone, 206, 246 Coumarins, 206, 249 Cranial, 206, 219, 227, 242 Craniocerebral Trauma, 195, 206, 219, 260 Creatinine, 28, 206, 228, 263 Critical Care, 68, 71, 81, 86, 93, 103, 126, 167, 206 Crossing-over, 206, 251 C-terminal, 36, 37, 206 Cues, 38, 39, 51, 206 Curative, 38, 52, 206, 260 Cutaneous, 198, 206 Cyclic, 206, 219, 238, 248 Cyclin, 45, 206 Cyclin-Dependent Kinases, 45, 206 Cyproterone, 206, 216 Cytochrome, 10, 12, 35, 98, 206, 207 Cytochrome-c Oxidase, 98, 207 Cytokine, 30, 33, 52, 95, 207 Cytomegalovirus, 207, 216 Cytomegalovirus Infections, 207, 216
Index 273
Cytoplasm, 193, 200, 207, 219, 235, 253 Cytoskeleton, 10, 207 Cytostatic, 31, 207, 236 Cytotoxic, 35, 49, 207, 250, 255 Cytotoxicity, 44, 189, 202, 207, 228 D Data Collection, 42, 207 De novo, 21, 207 Deamination, 207, 263 Decidua, 207, 244 Decompensation, 6, 14, 189, 207 Decompression, 42, 207 Degenerative, 168, 207, 221, 239 Dehydration, 131, 168, 207 Deletion, 193, 207 Dementia, 131, 192, 208 Denaturation, 208, 245 Dendrites, 208, 237 Dendritic, 12, 41, 208, 232 Dendritic cell, 12, 41, 208 Density, 208, 210, 215, 230 Depolarization, 208, 255 Depressive Disorder, 176, 208 Desiccation, 28, 208 Detergents, 208, 238 Detoxification, 16, 27, 39, 73, 208 Deuterium, 208, 223 Developmental Biology, 23, 25, 208 Diabetes Mellitus, 98, 170, 175, 208, 218, 220 Diagnostic procedure, 113, 135, 208, 243 Dialyzer, 208, 220 Diarrhea, 60, 154, 165, 208, 216, 231, 243 Diastolic, 208, 223 Diathesis, 32, 208 Diclofenac, 82, 208 Diclofenac Sodium, 208 Digestion, 52, 189, 196, 197, 208, 226, 230, 257 Digestive system, 111, 209, 235 Digestive tract, 162, 209, 256 Dihydrotestosterone, 209, 251 Dihydroxycholecalciferols, 116, 209 Dilatation, 191, 209, 249, 264 Dilatation, Pathologic, 209, 264 Dilate, 118, 209 Dilation, 197, 209, 264 Diploid, 209, 244 Direct, iii, 21, 29, 33, 36, 44, 52, 161, 209, 210, 251 Disaccharides, 29, 209 Discrete, 209, 267
Disease Progression, 24, 29, 209, 265 Disease Transmission, 125, 209 Disease Transmission, Horizontal, 209 Disease Transmission, Vertical, 209 Disinfectant, 209, 213, 233 Disparity, 8, 209 Distal, 42, 117, 209, 249 Dizziness, 152, 209 Dopamine, 192, 201, 203, 209, 238, 243 Drug Design, 22, 138, 139, 210 Drug Interactions, 18, 138, 210 Drug Resistance, 110, 210 Drug Tolerance, 210, 261 Drug Toxicity, 5, 210 Duct, 48, 114, 190, 198, 210, 214, 227, 253, 257 Ductal carcinoma in situ, 174, 210, 227 Ductus Arteriosus, 116, 117, 118, 210 Duodenum, 196, 210, 212, 221, 257 Dyslipidemia, 176, 210 Dysphoric, 208, 210 Dysplasia, 149, 210 Dyspnea, 207, 210 Dystrophy, 148, 210 E Eating Disorders, 170, 210 Edema, 4, 13, 35, 40, 64, 77, 83, 89, 97, 207, 210, 227, 236, 263 Effector, 36, 187, 203, 210, 228 Efficacy, 16, 29, 48, 72, 89, 106, 110, 210 Eicosanoids, 49, 127, 211 Ejaculation, 211, 254 Elastic, 38, 211, 218, 259 Elastin, 23, 203, 211, 214 Electrocoagulation, 202, 211 Electrolyte, 189, 205, 211, 220, 228, 234, 246, 256, 263 Electrophysiological, 82, 211 Electroplating, 199, 211 Elementary Particles, 211, 231, 238, 249 Emboli, 70, 211 Embolization, 70, 211 Embolus, 211, 225 Embryo, 196, 200, 211, 225, 233, 235 Embryogenesis, 211, 257 Emphysema, 23, 38, 131, 202, 211 Encephalopathy, 5, 6, 12, 26, 42, 55, 57, 104, 126, 148, 211 Endemic, 37, 211, 221, 232, 257 Endocarditis, 198, 211 Endogenous, 19, 24, 28, 37, 194, 209, 211, 212, 261
274
Liver Failure
Endorphins, 212, 238 Endoscope, 212 Endoscopic, 18, 42, 169, 212 Endoscopy, 122, 212 Endothelial cell, 10, 34, 212 Endothelium, 212, 238 Endothelium-derived, 212, 238 Endotoxemia, 44, 49, 50, 83, 127, 212 Endotoxic, 212, 230 Endotoxin, 44, 49, 50, 212, 263 End-stage renal, 18, 202, 212, 245 Enhancer, 49, 212 Enkephalins, 212, 238 Enterocolitis, 54, 212 Enteropeptidase, 212, 262 Environmental Exposure, 212, 239 Environmental Health, 144, 146, 212 Enzymatic, 39, 190, 198, 204, 206, 212, 245, 253 Enzyme Inhibitors, 212, 244 Epidemic, 28, 213, 257 Epidemiological, 8, 213, 214, 252 Epidermis, 213, 250 Epigastric, 213, 240 Epinephrine, 209, 213, 238, 263 Epithelial, 12, 23, 33, 48, 53, 114, 188, 199, 202, 207, 213, 221, 229 Epithelial Cells, 12, 33, 114, 213, 221, 229 Epithelium, 38, 195, 212, 213, 227, 267 Epitopes, 30, 213 Erythrocytes, 190, 197, 213, 251 Erythromycin, 202, 213 Esophageal, 43, 213 Esophagus, 209, 213, 243, 257, 264 Essential Tremor, 148, 213 Ethanol, 31, 32, 36, 213 Ethnic Groups, 154, 159, 213 Evacuation, 205, 213 Evoke, 213, 257 Excitation, 190, 213, 215, 237 Excrete, 193, 213, 228 Exhaustion, 213, 232 Exocrine, 214, 240 Exogenous, 16, 33, 49, 212, 214, 242, 263 Expectorant, 190, 214 External-beam radiation, 214, 227, 250, 266 Extracellular, 32, 33, 48, 50, 122, 194, 205, 214, 215, 232, 256, 259 Extracellular Matrix, 32, 33, 48, 50, 205, 214, 215, 232 Extracellular Matrix Proteins, 32, 214, 232
Extracellular Space, 214 Extracorporeal, 19, 27, 66, 73, 74, 94, 95, 106, 114, 214, 220 Extracorporeal Circulation, 19, 214 Extraction, 43, 214 Extravasation, 44, 214 Extravascular, 44, 214 Extremity, 214, 229, 241 F Facial, 85, 214 Facial Paralysis, 85, 214 Family Planning, 145, 214 Fat, 32, 188, 193, 196, 197, 205, 211, 214, 215, 228, 230, 235, 253, 256, 259, 262 Fatal Outcome, 7, 214 Fatigue, 54, 152, 155, 159, 161, 176, 214, 220, 241 Fatty acids, 6, 60, 188, 211, 215, 230, 247, 260 Fatty Liver, 31, 124, 125, 166, 215 Febrile, 215, 232, 257 Feces, 156, 198, 205, 215, 257 Fetal Blood, 210, 215 Fetoprotein, 215 Fetus, 117, 189, 215, 243 Fibrin, 196, 215, 242, 260 Fibrinogen, 215, 244, 248, 260 Fibroblasts, 51, 117, 118, 215 Fibronectins, 214, 215 Fibrosis, 21, 28, 32, 55, 58, 149, 189, 215, 254 Flatus, 215, 217 Flow Cytometry, 14, 53, 215 Flumazenil, 56, 215 Fluorescence, 13, 215, 216 Fluorescent Dyes, 215, 216 Fluorouracil, 216, 259 Flutamide, 76, 216 Fold, 54, 57, 216, 233, 239 Foodborne Illness, 168, 216 Forearm, 197, 216 Free Radicals, 32, 127, 192, 216 Frontal Lobe, 26, 216 Fulminant Hepatic Failure, 16, 31, 57, 109, 125, 216 Fungi, 189, 191, 204, 216, 234, 260, 266 Fungus, 198, 216 G Gallbladder, 122, 187, 196, 201, 209, 216, 221 Gallstones, 122, 161, 196, 201, 216, 264 Gamma Rays, 216, 236, 250
Index 275
Ganciclovir, 85, 216 Ganglia, 26, 187, 195, 216, 237, 242, 259 Ganglion, 217, 266 Gangrene, 63, 217 Gap Junctions, 51, 205, 217 Gas, 19, 190, 198, 215, 217, 223, 231, 236, 238, 265 Gas exchange, 19, 217 Gastric, 43, 117, 118, 194, 199, 217 Gastrin, 217, 222 Gastrointestinal tract, 116, 123, 198, 213, 217, 229, 255, 263 Gelsolin, 68, 217 Gemcitabine, 74, 217 Gene Expression, 27, 37, 49, 149, 217 Gene Therapy, 17, 23, 29, 32, 46, 85, 217 Genetic Code, 217, 238 Genetic Counseling, 154, 217 Genetic Engineering, 27, 196, 202, 218 Genetic testing, 218, 245 Genetics, 71, 204, 218 Genital, 218, 264 Genotype, 21, 24, 53, 218, 243 Gestation, 218, 242, 244 Gland, 188, 206, 218, 231, 240, 243, 248, 254, 257, 261 Glomerular, 218, 228, 252 Glucocorticoid, 74, 218, 246 Glucose, 42, 148, 197, 200, 208, 218, 219, 220, 225, 226, 254 Glucose Intolerance, 208, 218 Glucuronic Acid, 218, 221 Glutamate, 26, 218 Glutamic Acid, 218, 238, 247 Glutamine, 26, 57, 77, 218 Glutathione Peroxidase, 44, 218 Gluten, 199, 218 Glycine, 78, 190, 196, 201, 218, 238, 255 Glycoprotein, 15, 198, 215, 219, 229, 235, 263 Glycosaminoglycans, 214, 219 Glycoside, 209, 219, 253 Gonadal, 219, 257 Governing Board, 219, 246 Grade, 6, 12, 219 Graft, 9, 78, 87, 219, 222 Gram-negative, 212, 219 Granulocytes, 219, 229, 255, 266 Granulomas, 122, 219 Gravidity, 219, 241 Growth factors, 17, 33, 48, 53, 219, 234 Guanylate Cyclase, 219, 238
H Haemopoietic, 80, 219 Handwashing, 156, 219 Haploid, 219, 244 Headache, 152, 155, 219, 225 Headache Disorders, 219 Health Policy, 19, 220 Health Promotion, 158, 220 Health Services, 16, 19, 167, 220 Heart failure, 23, 117, 124, 131, 164, 167, 220 Heartbeat, 220, 258 Hematology, 75, 122, 220, 243 Heme, 196, 206, 220, 245 Hemochromatosis, 23, 69, 78, 91, 123, 124, 162, 220 Hemodiafiltration, 19, 103, 220, 263 Hemodialysis, 6, 81, 174, 208, 220, 228, 263 Hemodynamics, 96, 220 Hemofiltration, 68, 220, 263 Hemoglobin, 190, 213, 220 Hemoglobinopathies, 217, 220 Hemoglobinuria, 148, 220 Hemolytic, 92, 220 Hemophilia, 14, 24, 75, 149, 221 Hemorrhage, 15, 206, 211, 219, 221, 250, 258 Hemostasis, 97, 221, 255 Heparin, 19, 221 Hepatic Artery, 122, 221 Hepatic Encephalopathy, 4, 6, 18, 25, 56, 83, 94, 122, 123, 124, 126, 127, 157, 221 Hepatitis A, 45, 75, 78, 81, 90, 92, 95, 115, 123, 125, 131, 156, 159, 221 Hepatitis C, 15, 20, 21, 37, 59, 124, 130, 152, 153, 155, 156, 158, 159, 160, 161, 170, 171, 221 Hepatitis D, 21, 115, 221 Hepatitis Delta Virus, 21, 221 Hepatitis Viruses, 35, 125, 173, 221 Hepatoblastoma, 114, 221 Hepatocellular, 5, 15, 20, 26, 36, 41, 43, 45, 48, 51, 53, 69, 95, 109, 122, 125, 221 Hepatocellular carcinoma, 15, 20, 41, 43, 45, 48, 95, 125, 221 Hepatocyte, 4, 13, 17, 23, 25, 27, 28, 30, 31, 33, 34, 36, 38, 45, 48, 50, 51, 52, 69, 74, 79, 80, 89, 127, 201, 221 Hepatocyte Growth Factor, 79, 221 Hepatoma, 23, 221 Hepatorenal Syndrome, 6, 122, 123, 124, 221
276
Liver Failure
Hepatotoxic, 31, 38, 222 Hepatotoxicity, 34, 36, 39, 74, 222 Hepatovirus, 221, 222 Hereditary, 23, 153, 221, 222, 253 Heredity, 217, 218, 222 Herpes, 85, 222 Herpes Zoster, 222 Heterogeneity, 24, 188, 222 Hirsutism, 76, 206, 222, 223 Histocompatibility, 23, 222 Homeostasis, 13, 35, 36, 41, 122, 222 Homologous, 189, 205, 206, 217, 222, 254, 259 Homotypic, 51, 222 Hormonal, 194, 205, 222 Hormone, 39, 63, 135, 189, 205, 206, 211, 213, 217, 222, 226, 233, 240, 247, 253, 255, 259, 261 Hospitals, Public, 222, 224 Host, 9, 26, 29, 34, 38, 39, 44, 46, 78, 157, 195, 198, 199, 222, 224, 229, 258, 264, 265 Human growth hormone, 136, 222 Humoral, 222, 260 Hybrid, 16, 202, 222 Hybridization, 24, 27, 222 Hydrogen, 92, 187, 189, 195, 198, 208, 214, 218, 222, 223, 230, 235, 238, 240, 249, 266 Hydrogen Peroxide, 92, 218, 223, 230 Hydrolysis, 202, 223, 243, 248, 262 Hydroxylysine, 203, 223 Hydroxyproline, 190, 203, 223 Hyperammonemia, 13, 57, 223 Hyperbilirubinemia, 223, 228 Hypercholesterolemia, 210, 223 Hyperlipidemia, 210, 223 Hypersensitivity, 223, 229, 253 Hypertension, 16, 84, 116, 117, 124, 170, 223, 227, 245, 263 Hypertrichosis, 222, 223 Hypertriglyceridemia, 210, 223 Hypoglycemia, 4, 39, 223 Hypotension, 127, 192, 223 Hypotensive, 117, 118, 223 Hypothermia, 27, 81, 89, 90, 223 I Ibuprofen, 93, 223 Idiopathic, 82, 223 Ileostomy, 223, 236 Ileum, 53, 223 Immune Complex Diseases, 192, 223, 244 Immune Sera, 224
Immune system, 4, 21, 22, 26, 34, 155, 192, 195, 196, 224, 229, 231, 235, 264, 266 Immunity, 12, 14, 34, 46, 224, 262 Immunization, 81, 82, 130, 154, 155, 169, 224 Immunization Programs, 131, 224 Immunocompromised, 125, 224 Immunocompromised Host, 125, 224 Immunodeficiency, 12, 24, 46, 55, 75, 88, 148, 157, 163, 172, 224 Immunogenic, 224, 230 Immunoglobulin, 191, 224, 235 Immunologic, 29, 54, 201, 224, 250 Immunology, 15, 34, 45, 62, 70, 188, 216, 224 Immunosuppressant, 136, 216, 224 Immunosuppressive, 14, 33, 54, 218, 224 Impairment, 121, 194, 201, 224, 233 Implant radiation, 224, 226, 227, 250, 266 In situ, 49, 224 In vitro, 13, 15, 17, 21, 24, 25, 28, 32, 33, 38, 39, 44, 46, 48, 51, 58, 217, 224, 245, 258, 261 In vivo, 10, 16, 17, 21, 24, 25, 28, 32, 34, 36, 38, 41, 44, 48, 57, 82, 117, 217, 221, 224, 260 Incision, 224, 227, 229 Incubation, 29, 225 Indicative, 125, 225, 241, 264 Indolent, 53, 225 Induction, 25, 32, 36, 49, 62, 190, 192, 225, 250 Infancy, 90, 122, 135, 153, 225 Infarction, 77, 225, 244, 252 Infiltration, 61, 79, 225, 247, 267 Influenza, 162, 225 Information Systems, 19, 225 Infusion, 49, 69, 72, 96, 106, 110, 225, 262 Ingestion, 4, 10, 36, 225, 236, 244, 259 Inhalation, 225, 244 Initiation, 24, 36, 225, 261 Inorganic, 202, 225 Inositol, 26, 77, 225 Insecticides, 225, 266 Insight, 23, 225 Insulator, 226, 235 Insulin, 31, 42, 83, 226, 228, 263 Insulin-dependent diabetes mellitus, 226 Intensive Care, 4, 127, 226 Intercellular Junctions, 33, 226 Interferon, 14, 20, 21, 24, 37, 48, 76, 157, 226, 231
Index 277
Interferon-alpha, 226 Interleukin-1, 14, 226 Interleukin-10, 14, 226 Interleukin-2, 226 Intermittent, 226, 231 Internal Medicine, 5, 7, 15, 22, 24, 39, 61, 85, 91, 97, 98, 100, 106, 220, 226 Internal radiation, 226, 227, 250, 266 Interstitial, 197, 214, 226, 227, 252, 266 Intestinal, 52, 54, 83, 136, 166, 199, 201, 212, 226, 231 Intestinal Mucosa, 199, 212, 226 Intracellular, 10, 12, 13, 15, 23, 37, 70, 225, 227, 233, 238, 246, 248, 251, 255 Intracellular Membranes, 227, 233 Intracranial Hypertension, 81, 89, 219, 227 Intracranial Pressure, 65, 69, 90, 100, 227, 249 Intraductal carcinoma, 210, 227 Intrahepatic, 14, 16, 42, 53, 55, 56, 227 Intramuscular, 23, 227, 240 Intramuscular injection, 23, 227 Intraocular, 227, 239 Intraocular pressure, 227, 239 Intraperitoneal, 106, 227 Intravascular, 70, 227 Intravenous, 23, 110, 131, 152, 225, 227, 240 Invasive, 54, 58, 76, 174, 224, 227, 231 Involuntary, 195, 213, 227, 236, 256 Ion Channels, 194, 227, 243 Ions, 195, 211, 217, 223, 227, 248 Iris, 193, 202, 205, 227 Irradiation, 116, 227, 252, 266 Ischemia, 9, 13, 28, 44, 194, 227, 252 Isoniazid, 36, 60, 69, 228 J Jaundice, 5, 84, 122, 123, 124, 126, 130, 155, 158, 161, 221, 223, 228 Joint, 45, 152, 168, 193, 228, 239, 259 K Kava, 18, 60, 228 Kb, 144, 228 Keto, 116, 228, 261 Ketoconazole, 75, 228 Ketone Bodies, 39, 187, 228 Kidney Disease, 34, 109, 110, 111, 136, 144, 149, 171, 228 Kidney Failure, 28, 127, 131, 158, 212, 228 Kidney Failure, Acute, 228 Kidney Failure, Chronic, 228 Kidney Transplantation, 136, 228
Killer Cells, 228 Kinetic, 24, 228, 242 L Labile, 203, 229 Laminin, 195, 214, 229 Lamivudine, 101, 110, 229 Laparoscopy, 169, 229 Laparotomy, 54, 229 Large Intestine, 203, 209, 226, 229, 251, 256, 266 Latent, 163, 229 Lectin, 229, 233 Leg Ulcer, 169, 229 Lethal, 13, 85, 195, 229, 236 Leucocyte, 189, 229, 231 Leukemia, 79, 148, 217, 229 Leukocytes, 197, 201, 219, 226, 229, 235, 263 Leukotrienes, 193, 211, 229 Library Services, 182, 229 Lidocaine, 16, 229 Life cycle, 21, 216, 229 Life Expectancy, 55, 229 Ligament, 229, 248 Ligands, 24, 49, 230 Ligation, 33, 44, 230 Lipid, 42, 201, 226, 228, 230, 235, 240, 262 Lipid A, 42, 230 Lipid Peroxidation, 230, 240 Lipopolysaccharide, 62, 106, 219, 230 Lipoprotein, 210, 219, 230, 231, 265 Liposomes, 29, 230 Lipoxygenase, 49, 193, 229, 230 Liver cancer, 56, 93, 131, 132, 153, 154, 155, 156, 157, 158, 159, 160, 162, 189, 230 Liver Circulation, 122, 230 Liver Cirrhosis, 95, 131, 132, 221, 230 Liver Enzyme Tests, 84, 230 Liver Regeneration, 32, 230 Lobe, 222, 230 Localization, 42, 51, 230 Localized, 190, 222, 223, 225, 229, 230, 244, 254 Locomotion, 230, 244 Longitudinal study, 47, 230 Long-Term Care, 16, 231 Low-density lipoprotein, 210, 230, 231 Lymph, 12, 202, 212, 231 Lymph node, 12, 231 Lymphatic, 212, 225, 231, 256, 257, 260 Lymphatic system, 231, 256, 257, 260 Lymphoblastic, 231
278
Liver Failure
Lymphoblasts, 187, 231 Lymphocyte, 14, 192, 228, 231, 232 Lymphocytic, 231 Lymphoid, 41, 191, 229, 231 Lymphoma, 68, 75, 77, 79, 93, 102, 148, 231 Lymphoproliferative, 136, 231 Lysine, 223, 231, 262 M Macrophage, 226, 231 Magnetic Resonance Imaging, 122, 231, 254 Magnetic Resonance Spectroscopy, 103, 231 Malabsorption, 148, 199, 231, 255 Malabsorption syndrome, 231, 255 Malaria, 102, 232 Malaria, Falciparum, 232 Malaria, Vivax, 232 Malignancy, 25, 232 Malignant, 37, 65, 76, 91, 122, 123, 148, 188, 192, 199, 230, 232, 237, 247, 250 Malignant tumor, 123, 199, 232 Malnutrition, 131, 135, 188, 194, 232, 236 Manic, 192, 196, 232 Man-made, 199, 232 Matrix metalloproteinase, 40, 232 Mediate, 15, 49, 209, 228, 232 Mediator, 37, 226, 232, 255 Medical Records, 232, 253 Medication Errors, 166, 232 MEDLINE, 145, 147, 149, 232 Megakaryocytes, 197, 232, 260 Melanin, 227, 232, 243, 263 Melanocytes, 232, 233 Melanoma, 148, 233 Membrane Proteins, 41, 230, 233 Memory, 208, 233 Menarche, 22, 233, 252 Meninges, 200, 206, 233 Menopause, 22, 233, 252 Menstruation, 207, 233, 252 Mental, iv, 7, 111, 131, 144, 146, 150, 158, 200, 201, 203, 208, 214, 233, 249, 263, 264 Mental Disorders, 111, 233, 249 Mental Health, iv, 7, 111, 144, 146, 233, 249 Mentors, 25, 31, 56, 233 Mercuric Chloride, 28, 233 Mercury, 215, 233 Mesenteric, 12, 106, 233, 245 Mesentery, 233, 242, 257 Mesoderm, 25, 233, 262
Metabolic disorder, 4, 13, 125, 223, 233 Metabolite, 26, 35, 39, 117, 118, 233, 247 Metastasis, 165, 232, 233, 234, 237 Metastatic, 98, 234, 254 MI, 62, 76, 86, 92, 156, 185, 234 Microbe, 234, 261 Microbiology, 45, 90, 188, 234 Microcirculation, 118, 230, 234 Microglia, 194, 234 Microorganism, 203, 234, 241, 265 Micro-organism, 22, 234 Microscopy, 10, 25, 195, 234 Migration, 44, 234 Mineralocorticoids, 188, 205, 234 Mitosis, 193, 234 Mobility, 29, 234 Modeling, 12, 19, 41, 47, 210, 234 Modification, 27, 190, 218, 234, 250, 266 Modulator, 21, 234 Monitor, 80, 157, 198, 206, 235, 238 Monoclonal, 40, 227, 235, 250, 266 Monoclonal antibodies, 40, 235 Monocytes, 226, 229, 235 Monogenic, 23, 235 Mononuclear, 14, 235, 263 Morphogenesis, 15, 235 Morphological, 57, 211, 216, 232, 235 Morphology, 220, 235 Morula, 196, 235 Motility, 217, 235, 255 Motion Sickness, 235, 236 Mucins, 235, 253 Mucolytic, 187, 197, 235 Mucositis, 235, 260 Multiple Organ Failure, 19, 235 Multiple sclerosis, 76, 235 Muscle Fibers, 235, 236 Muscle Relaxation, 235, 237 Muscular Atrophy, 148, 236 Muscular Diseases, 214, 236 Muscular Dystrophies, 210, 236 Mushroom Poisoning, 4, 236 Mustard Gas, 236 Mutagen, 21, 236 Myalgia, 225, 236 Myelin, 235, 236 Myocardial infarction, 18, 68, 164, 205, 234, 236 Myocardium, 234, 236 Myopathy, 39, 236 Myotonic Dystrophy, 148, 236
Index 279
N Narcolepsy, 173, 236 Nasal Mucosa, 225, 236 Natural killer cells, 34, 236 Nausea, 155, 156, 159, 191, 192, 236, 249, 263 NCI, 1, 24, 111, 143, 236 Necrotizing Enterocolitis, 52, 236 Neonatal, 55, 69, 91, 167, 236 Neoplasia, 148, 237 Neoplasms, 192, 198, 237, 250, 260 Neoplastic, 231, 237 Nephropathy, 18, 228, 237 Nephrosis, 222, 237 Nephrotoxic, 6, 237 Nerve, 13, 191, 194, 201, 208, 214, 217, 232, 235, 237, 246, 247, 249, 253, 254, 257, 262, 266 Nervous System, 82, 148, 187, 190, 195, 200, 203, 217, 218, 229, 232, 234, 235, 237, 241, 242, 245, 255, 259 Neural, 57, 215, 222, 234, 237 Neuroleptic, 76, 91, 192, 237 Neurologic, 26, 94, 237 Neurology, 76, 100, 103, 237 Neuromuscular, 158, 167, 187, 214, 237, 263 Neuromuscular Blockade, 167, 237 Neuromuscular Junction, 187, 237 Neuronal, 35, 237 Neurons, 13, 35, 203, 208, 216, 237, 259 Neuropsychological Tests, 26, 56, 237 Neurotoxicity, 57, 237 Neurotoxin, 57, 237 Neurotransmitter, 13, 56, 57, 187, 188, 190, 197, 209, 218, 227, 237, 238, 255, 258 Neutrons, 189, 227, 238, 250 Neutrophil, 23, 44, 92, 238 Neutrophil Activation, 44, 238 Nitric Oxide, 10, 50, 57, 104, 122, 238 Nitrogen, 126, 189, 190, 214, 218, 228, 238, 262 Nonoxynol, 152, 238 Norepinephrine, 209, 238 Nuclear, 37, 39, 49, 195, 204, 216, 217, 232, 238, 247, 250 Nuclei, 32, 189, 204, 214, 217, 218, 231, 234, 238, 249 Nucleic acid, 12, 198, 217, 222, 238, 250, 253, 266 Nucleic Acid Hybridization, 222, 238 Nucleoprotein, 221, 238
Nucleus, 193, 195, 201, 206, 207, 208, 211, 216, 235, 238, 239, 249, 257, 260 Nursing Care, 239, 241 Nutritional Status, 165, 239 O Occult, 5, 239 Occupational Exposure, 22, 239 Ocular, 116, 117, 118, 239 Ocular Hypertension, 116, 117, 118, 239 Oliguria, 228, 239 Omentum, 221, 239 Oncogene, 148, 221, 239, 257 Oncogenic, 46, 239 Organ Culture, 239, 261 Organ Transplantation, 13, 19, 87, 239 Organogenesis, 114, 239 Osmolality, 63, 239 Osmoles, 239 Osmosis, 239 Osmotic, 13, 35, 188, 239 Osteoarthritis, 174, 239 Ovalbumin, 12, 239 Overdose, 3, 4, 52, 83, 126, 134, 216, 240 Ovum, 207, 218, 229, 235, 240, 247, 262, 266 Oxidation, 36, 39, 187, 192, 193, 206, 218, 230, 240 Oxidative Stress, 32, 57, 240 Oxygen Consumption, 79, 240, 252 Oxygenation, 27, 81, 117, 240 Oxygenator, 19, 240 P Palliative, 172, 206, 240, 260 Pancreas, 122, 123, 187, 209, 220, 221, 226, 240, 257, 262, 263 Pancreatic, 148, 240 Pancreatic cancer, 148, 240 Pancreatitis, 77, 240 Paracentesis, 122, 240 Paradoxical, 14, 240 Parasite, 13, 240 Parathyroid, 116, 240, 259 Parathyroid Glands, 240 Parenteral, 14, 52, 65, 136, 166, 240, 241 Parenteral Nutrition, 52, 136, 166, 241 Paresis, 214, 241 Parietal, 26, 241, 242 Parietal Lobe, 26, 241 Parity, 22, 241 Paroxysmal, 148, 220, 241 Pathogen, 225, 241, 258
280
Liver Failure
Pathogenesis, 13, 21, 29, 34, 39, 40, 45, 50, 53, 55, 57, 94, 121, 126, 127, 158, 241 Pathologic, 31, 94, 187, 193, 196, 198, 205, 223, 241 Pathologic Processes, 193, 241 Pathophysiology, 10, 13, 15, 26, 50, 67, 83, 241 Patient Care Management, 157, 241 Patient Education, 152, 157, 160, 161, 180, 182, 185, 241 Patient Selection, 157, 241 Pelvic, 157, 241, 248 Pelvic inflammatory disease, 157, 241 Pelvis, 187, 241 Pemoline, 82, 241 Penicillamine, 71, 241 Penicillin, 241, 264 Penis, 204, 211, 241 Peptide, 37, 122, 190, 202, 212, 242, 248 Peptide Chain Elongation, 202, 242 Percutaneous, 165, 242 Perforation, 54, 242, 266 Perfusion, 19, 27, 30, 49, 73, 74, 97, 106, 114, 117, 196, 242 Perinatal, 56, 117, 174, 242 Perioperative, 164, 242 Peripheral blood, 55, 189, 226, 242 Peripheral Nervous System, 212, 237, 242, 258 Peristalsis, 117, 118, 242 Peritoneal, 54, 194, 227, 242 Peritoneal Cavity, 194, 227, 242 Peritoneum, 233, 239, 242 Peritonitis, 15, 99, 122, 123, 124, 242, 266 Pharmacokinetics, 210, 242 Pharmacologic, 42, 51, 191, 242, 261 Pharmacotherapy, 76, 93, 242 Pharynx, 225, 243 Phenotype, 17, 32, 39, 243 Phenprocoumon, 81, 243 Phenylalanine, 243, 263 Phenytoin, 198, 243 Phlebotomy, 162, 243 Phospholipases, 243, 255 Phospholipids, 214, 225, 230, 243 Phosphorus, 94, 103, 116, 198, 240, 243 Phosphorylation, 206, 207, 243 Photocoagulation, 202, 243 Physiologic, 14, 19, 20, 32, 49, 64, 188, 233, 243, 247, 251 Physiology, 13, 106, 122, 211, 220, 243, 258 Pilot study, 7, 40, 43, 46, 78, 243
Pituitary Gland, 205, 243 Placenta, 117, 215, 243, 247 Plants, 115, 189, 198, 201, 203, 218, 219, 229, 235, 238, 244, 253, 261 Plasma cells, 191, 244 Plasma Exchange, 64, 81, 96, 103, 244 Plasma protein, 38, 188, 244, 248 Plasmapheresis, 71, 79, 244 Plasticity, 48, 244 Platelet Activation, 244, 255 Platelet Aggregation, 189, 190, 238, 244, 248, 260 Platelets, 238, 244, 260 Platinum, 202, 244 Pneumonia, 167, 173, 205, 244, 262 Poisoning, 52, 210, 216, 233, 236, 244 Polyarteritis Nodosa, 100, 224, 244 Polycystic, 149, 244 Polymerase, 5, 21, 43, 192, 245 Polymerase Chain Reaction, 5, 43, 245 Polymorphism, 101, 245 Polyposis, 203, 245 Polysaccharide, 191, 200, 245, 248 Pons, 214, 245 Population Dynamics, 41, 245 Porphyria, 243, 245 Porphyria Cutanea Tarda, 243, 245 Portal Hypertension, 16, 45, 71, 75, 122, 123, 124, 161, 245 Portal System, 42, 245 Portal Vein, 77, 125, 245 Portosystemic Shunt, 56, 245 Posterior, 190, 193, 194, 227, 240, 245 Postnatal, 245, 257 Postoperative, 55, 64, 70, 72, 79, 85, 95, 96, 101, 106, 122, 124, 136, 235, 246 Postsynaptic, 246, 255 Potassium, 189, 234, 246 Potentiates, 10, 226, 246 Potentiation, 10, 246, 255 Practice Guidelines, 146, 162, 163, 164, 167, 175, 246 Preceptorship, 20, 246 Precipitating Factors, 158, 199, 220, 246 Precipitation, 56, 246 Preclinical, 12, 246 Precursor, 191, 193, 201, 209, 210, 212, 238, 243, 246, 247, 248, 262, 263, 264 Predictive factor, 94, 246 Prednisolone, 246 Prednisone, 135, 246 Preoperative, 9, 79, 127, 162, 246
Index 281
Presynaptic, 237, 246 Prevalence, 5, 31, 57, 130, 246 Primary Biliary Cirrhosis, 122, 124, 161, 171, 246 Primary Sclerosing Cholangitis, 43, 124, 161, 246 Procaine, 229, 247 Prodrug, 116, 247 Progeny, 52, 204, 247 Progesterone, 247, 257 Prognostic factor, 4, 16, 62, 130, 247 Progression, 10, 12, 14, 24, 33, 34, 43, 46, 55, 58, 83, 162, 191, 206, 247, 263 Proliferating Cell Nuclear Antigen, 32, 247 Proline, 203, 223, 247 Promoter, 5, 24, 37, 48, 247 Prophylaxis, 122, 172, 173, 192, 247, 253, 264 Proportional, 239, 247 Prospective study, 97, 230, 247 Prostaglandin, 72, 96, 106, 117, 118, 247, 248, 260 Prostaglandin Endoperoxides, 248, 260 Prostaglandins A, 117, 118, 247, 248 Prostaglandins D, 248 Prostaglandins H, 118, 248 Prostate, 148, 248, 263 Prostheses and Implants, 194, 248 Protease, 23, 248 Protein C, 188, 190, 195, 230, 248, 263, 265 Protein S, 21, 149, 193, 196, 202, 213, 217, 222, 248, 253 Proteoglycans, 195, 214, 248 Proteolytic, 38, 189, 203, 212, 215, 248 Prothrombin, 6, 32, 248, 260 Prothrombin Time, 6, 32, 248 Protocol, 14, 249 Protons, 189, 207, 223, 231, 249, 250 Protozoa, 204, 234, 249 Protozoan, 200, 232, 249 Proximal, 49, 209, 246, 249 Pruritus, 54, 249, 263 Pseudotumor Cerebri, 227, 249 Psychiatric, 11, 47, 173, 233, 249 Psychiatry, 10, 47, 60, 249 Psychic, 233, 249, 254 Psychomotor, 198, 237, 249 Public Health, 20, 31, 47, 146, 172, 174, 249 Public Policy, 145, 249 Pulmonary, 19, 23, 38, 49, 97, 117, 197, 205, 210, 220, 228, 229, 249, 259, 265
Pulmonary Artery, 197, 210, 249, 265 Pulmonary Circulation, 117, 249 Pulmonary Edema, 228, 249 Pulmonary Emphysema, 23, 249 Pulse, 74, 235, 249 Purines, 249, 255 Purpura, 100, 250 Putrefaction, 217, 250 Pyrazinamide, 69, 250 Pyridoxal, 250, 261 Pyrimidines, 250, 255 Q Quality of Life, 16, 42, 43, 55, 162, 250 Quiescent, 32, 50, 250 R Race, 8, 19, 22, 234, 250 Radiation, 162, 187, 211, 212, 214, 215, 216, 224, 226, 227, 232, 250, 254, 266 Radiation therapy, 187, 214, 226, 227, 250, 266 Radioactive, 223, 224, 226, 227, 232, 235, 238, 239, 250, 254, 263, 266 Radioactivity, 250 Radiofrequency ablation, 162, 250 Radiolabeled, 227, 250, 266 Radiological, 242, 250 Radiology, 25, 122, 165, 174, 250 Radionuclide scanning, 71, 250 Radiotherapy, 197, 227, 250, 266 Raffinose, 29, 251 Raltitrexed, 74, 251 Randomized, 4, 6, 7, 11, 15, 18, 42, 43, 48, 55, 110, 211, 251 Randomized clinical trial, 15, 18, 42, 251 Reactivation, 80, 251 Reactive Oxygen Species, 50, 57, 251 Reagent, 21, 251 Receptor, 15, 23, 36, 39, 44, 52, 56, 116, 117, 118, 188, 192, 202, 209, 215, 221, 251, 255 Receptors, Serotonin, 251, 255 Recombinant, 15, 23, 25, 33, 82, 97, 136, 157, 196, 251, 265 Recombination, 14, 204, 217, 251 Reconstitution, 14, 251 Rectum, 193, 197, 203, 209, 215, 217, 229, 248, 251 Recurrence, 110, 136, 196, 251 Red blood cells, 213, 220, 245, 251, 254 Red Nucleus, 194, 251 Reductase, 69, 90, 251 Refer, 1, 203, 209, 212, 216, 222, 230, 237, 238, 251, 261
282
Liver Failure
Refraction, 251, 256 Refractory, 16, 37, 122, 211, 252 Regeneration, 4, 9, 52, 78, 127, 251, 252 Regimen, 11, 210, 242, 252 Relapse, 47, 48, 252 Remission, 196, 251, 252 Renal Circulation, 122, 252 Renal failure, 6, 116, 122, 221, 252 Renin, 122, 127, 191, 252 Reperfusion, 9, 44, 252 Reperfusion Injury, 252 Replicon, 21, 252 Repopulation, 34, 252 Reproductive History, 22, 252 Resection, 32, 49, 52, 54, 95, 123, 252, 255 Residential Facilities, 131, 252 Respiration, 198, 235, 252, 253 Response rate, 24, 252 Restoration, 251, 252, 253, 266 Resuscitation, 44, 253 Retinal, 209, 253 Retinoblastoma, 148, 253 Retinoids, 253, 265 Retrospective, 8, 24, 39, 46, 80, 253 Retrospective study, 80, 253 Retroviral vector, 217, 253 Rheumatism, 223, 253 Rheumatoid, 167, 171, 253 Rheumatoid arthritis, 167, 171, 253 Ribavirin, 14, 20, 21, 24, 253 Ribosome, 253, 262 Rigidity, 227, 244, 253 Risk factor, 9, 39, 46, 89, 95, 127, 130, 131, 132, 156, 157, 159, 199, 247, 253 Risk patient, 42, 253 Rod, 195, 212, 253 S Saliva, 156, 253 Salivary, 207, 209, 240, 253 Salivary glands, 207, 209, 253 Saphenous, 117, 118, 253 Saphenous Vein, 117, 118, 253 Saponins, 253, 257 Satellite, 221, 254 Scans, 250, 254 Scleroderma, 54, 254 Sclerosis, 148, 235, 254 Screening, 24, 43, 157, 170, 202, 254 Secondary tumor, 233, 254 Secretion, 14, 23, 49, 63, 83, 117, 118, 206, 226, 234, 235, 254 Secretory, 52, 114, 254
Sedative, 215, 228, 254 Segregation, 251, 254 Seizures, 13, 198, 241, 243, 254 Semen, 41, 154, 156, 158, 159, 211, 248, 254 Semisynthetic, 202, 254 Senile, 131, 254 Sensor, 117, 254 Sepsis, 4, 19, 31, 44, 49, 254 Septic, 4, 50, 68, 167, 194, 255 Sequencing, 24, 245, 255 Serine, 23, 255, 262 Serotonin, 56, 192, 238, 242, 251, 255, 262 Serous, 194, 212, 255 Sex Determination, 149, 255 Sex Education, 157, 255 Sexual Partners, 131, 155, 255 Sexually Transmitted Diseases, 153, 157, 255 Shock, 4, 9, 44, 50, 68, 87, 106, 167, 212, 255, 262 Short Bowel Syndrome, 70, 75, 166, 255 Shunt, 16, 42, 56, 255 Side effect, 18, 21, 28, 124, 130, 137, 139, 157, 188, 192, 196, 255, 261, 266 Signal Transduction, 33, 35, 37, 225, 255 Signs and Symptoms, 157, 244, 252, 255, 263 Skeletal, 23, 39, 190, 236, 255 Skeleton, 187, 228, 247, 255, 256 Skin test, 256, 263 Skull, 206, 227, 256, 259 Small intestine, 136, 201, 210, 222, 223, 226, 256, 262 Smooth muscle, 117, 118, 189, 190, 236, 248, 256, 258 Sneezing, 159, 160, 256 Social Environment, 250, 256 Sodium, 100, 189, 208, 234, 256 Soft tissue, 197, 256 Solid tumor, 191, 256 Solvent, 116, 187, 213, 239, 256 Soma, 256 Somatic, 53, 211, 222, 234, 239, 242, 256 Spatial disorientation, 209, 256 Specialist, 4, 177, 209, 256 Specificity, 18, 24, 49, 188, 193, 256 Spectrum, 9, 123, 157, 228, 234, 256 Sperm, 160, 161, 190, 201, 257 Spinal cord, 194, 200, 201, 217, 233, 237, 242, 257, 259 Spirochete, 257, 259 Splanchnic Circulation, 122, 257
Index 283
Spleen, 153, 190, 207, 231, 257 Splenic Vein, 245, 257 Sporadic, 36, 157, 245, 253, 257 Sprue, 165, 257 Stasis, 28, 257 Steatosis, 31, 215, 257 Stellate, 32, 50, 257 Stem Cell Factor, 52, 202, 257 Stem Cells, 17, 25, 38, 48, 52, 257 Stenosis, 257, 258 Sterile, 194, 240, 257, 262 Sterility, 14, 157, 257 Steroid, 134, 196, 206, 253, 257 Stimulant, 241, 257, 264 Stimulus, 33, 205, 213, 227, 257, 260 Stomach, 155, 187, 194, 209, 213, 217, 221, 222, 236, 239, 242, 243, 256, 257, 266 Stool, 203, 229, 257 Strand, 21, 245, 257 Street Drugs, 153, 160, 257 Streptococcal, 76, 258 Streptococcus, 258 Stress, 27, 31, 37, 195, 199, 206, 236, 240, 253, 258 Stricture, 122, 257, 258 Stroke, 18, 35, 111, 144, 258 Stromal, 197, 258 Stromal Cells, 197, 258 Subacute, 56, 75, 80, 81, 92, 93, 97, 99, 225, 258 Subarachnoid, 219, 258 Subclinical, 225, 254, 258 Subcutaneous, 210, 240, 258 Subspecies, 256, 258 Substance P, 213, 233, 251, 254, 258 Substrate, 36, 212, 258 Sudden death, 40, 258 Sulfur, 214, 229, 258 Superinfection, 76, 258 Superoxide, 10, 92, 258 Supplementation, 78, 258 Suppression, 27, 157, 206, 258, 259 Suppressive, 117, 118, 259 Surfactant, 238, 259, 266 Survival Rate, 32, 259 Sympathetic Nervous System, 122, 127, 195, 259 Symphysis, 201, 248, 259 Symptomatic, 24, 240, 259 Synaptic, 238, 255, 259 Syphilis, 163, 259 Systemic disease, 122, 124, 259
Systolic, 223, 259 T Taurine, 35, 196, 201, 259 Tegafur, 67, 259 Telangiectasia, 149, 259 Telencephalon, 195, 200, 259 Temporal, 5, 10, 30, 219, 259 Testosterone, 251, 259 Tetany, 240, 259 Thalamic, 194, 260 Thalamic Diseases, 194, 260 Therapeutics, 3, 5, 98, 99, 138, 260 Thermal, 238, 245, 260 Thorax, 187, 260 Threonine, 255, 260 Threshold, 223, 260 Thrombin, 215, 244, 248, 260 Thrombocytopenia, 19, 260 Thromboembolism, 173, 260 Thromboplastin, 248, 260 Thrombopoietin, 79, 260 Thrombosis, 19, 77, 248, 258, 260 Thromboxanes, 193, 211, 248, 260 Thrombus, 205, 225, 244, 260 Thrush, 198, 260 Thymidine, 85, 260 Thymidine Kinase, 85, 260 Thymus, 117, 118, 224, 231, 260 Thyroid, 74, 131, 164, 240, 261, 263 Thyroid Gland, 240, 261 Thyroiditis, 54, 261 Thyroxine, 188, 243, 261 Tissue, 7, 9, 13, 20, 24, 25, 27, 29, 32, 38, 39, 41, 43, 49, 51, 52, 53, 127, 160, 161, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 198, 201, 202, 205, 208, 210, 211, 214, 215, 216, 217, 219, 223, 224, 225, 226, 229, 230, 231, 232, 233, 235, 236, 237, 239, 240, 241, 242, 243, 244, 245, 248, 250, 252, 255, 256, 257, 258, 259, 261, 262, 264, 266 Tissue Culture, 27, 261 Tolerance, 25, 62, 188, 218, 261 Tomography, 56, 204, 231, 254, 261 Tooth Preparation, 188, 261 Topical, 194, 213, 223, 233, 261 Torsion, 225, 261 Toxic, iv, 4, 10, 13, 32, 36, 51, 124, 125, 204, 207, 212, 222, 224, 233, 236, 237, 242, 261, 266 Toxicity, 7, 36, 38, 39, 52, 84, 124, 210, 233, 258, 261
284
Liver Failure
Toxicology, 44, 66, 146, 261 Toxin, 39, 212, 261 Trachea, 214, 243, 261 Track and Field, 129, 261 Transaminase, 34, 261 Transcriptase, 229, 261, 266 Transcription Factors, 32, 37, 39, 49, 261 Transduction, 23, 255, 262 Transfection, 33, 39, 49, 196, 217, 262 Transfer Factor, 224, 262 Transfusion, 10, 96, 102, 221, 262 Translation, 27, 32, 190, 213, 262 Translational, 45, 53, 262 Translocation, 49, 202, 213, 262 Transmitter, 187, 194, 209, 227, 232, 238, 262 Trauma, 9, 13, 122, 123, 240, 262 Treatment Failure, 48, 262 Trifluoperazine, 58, 262 Triglyceride, 42, 223, 262 Trimethoprim-sulfamethoxazole, 99, 262 Troglitazone, 82, 262 Trophoblast, 196, 262 Trypsin, 23, 212, 262 Tryptophan, 203, 255, 262 Tubercle, 262, 263 Tuberculin, 163, 262, 263 Tuberculin Test, 163, 263 Tuberculostatic, 228, 263 Tuberous Sclerosis, 149, 263 Tumor marker, 163, 263 Tumor model, 46, 263 Tumor Necrosis Factor, 14, 263 Tumorigenic, 14, 263 Type 2 diabetes, 171, 175, 263 Tyrosine, 36, 209, 263 U Ulcerative colitis, 247, 263 Ultrafiltration, 220, 263 Unconscious, 223, 263 Uraemia, 240, 263 Urea, 16, 71, 228, 263 Uremia, 228, 252, 263 Ureters, 264 Urethra, 241, 248, 264 Urinary, 22, 239, 263, 264 Urinary tract, 22, 264 Urinary tract infection, 22, 264 Urine, 11, 39, 130, 155, 156, 191, 193, 196, 206, 220, 228, 239, 264 Ursodeoxycholic Acid, 43, 54, 264
V Vaccination, 131, 153, 160, 264 Vaccine, 15, 29, 123, 125, 156, 159, 161, 176, 249, 264 Vagina, 198, 233, 264 Vaginal, 152, 154, 156, 158, 159, 168, 238, 264 Vaginal Discharge, 168, 264 Vaginitis, 198, 264 Valine, 241, 264 Varicella, 92, 103, 264 Varices, 15, 43, 161, 264 Varicose, 229, 264 Varicose Ulcer, 229, 264 Vascular Resistance, 49, 264 Vasculitis, 240, 244, 264 Vasoconstriction, 50, 127, 213, 264 Vasodilation, 122, 264 Vasodilator, 189, 197, 210, 264 VE, 10, 265 Vector, 15, 23, 262, 265 Vein, 85, 117, 118, 122, 191, 193, 227, 238, 243, 245, 253, 254, 257, 265 Venereal, 259, 265 Venous, 24, 63, 118, 122, 173, 193, 207, 229, 248, 264, 265 Ventricle, 249, 259, 265 Venules, 44, 197, 198, 234, 265 Veterinary Medicine, 145, 265 Villous, 199, 265 Vinca Alkaloids, 265 Vinorelbine, 98, 265 Viral Load, 43, 110, 265 Viral vector, 32, 265 Viremia, 30, 265 Virion, 15, 221, 265 Virulence, 258, 261, 265 Virus Diseases, 192, 265 Viscosity, 187, 265 Vitamin A, 154, 225, 265 Vitro, 15, 17, 25, 32, 38, 44, 48, 221, 265 Vivo, 10, 17, 25, 29, 38, 41, 44, 49, 58, 67, 106, 266 Voluntary Health Agencies, 224, 266 Volvulus, 52, 266 Voriconazole, 86, 266 W Waiting Lists, 28, 266 Weight Gain, 153, 266 Wetting Agents, 238, 266 White blood cell, 157, 187, 191, 201, 229, 231, 236, 238, 244, 266
Index 285
Windpipe, 243, 261, 266 Womb, 117, 118, 266 Wound Healing, 232, 266 X Xenobiotics, 22, 266 Xenograft, 95, 191, 263, 266 X-ray, 204, 215, 216, 227, 232, 236, 238, 250, 254, 266
X-ray therapy, 227, 266 Y Yeasts, 198, 216, 243, 266 Z Zalcitabine, 229, 266 Zoster, 92, 103, 266 Zygote, 204, 267
286
Liver Failure
Index 287
288
Liver Failure
