LIVER DAMAGE 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 Damage: 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: 0-597-84517-4 1. Liver Damage-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 damage. 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 DAMAGE ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Liver Damage................................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 37 The National Library of Medicine: PubMed ................................................................................ 38 CHAPTER 2. NUTRITION AND LIVER DAMAGE............................................................................... 83 Overview...................................................................................................................................... 83 Finding Nutrition Studies on Liver Damage............................................................................... 83 Federal Resources on Nutrition ................................................................................................... 85 Additional Web Resources ........................................................................................................... 86 CHAPTER 3. ALTERNATIVE MEDICINE AND LIVER DAMAGE ........................................................ 89 Overview...................................................................................................................................... 89 The Combined Health Information Database............................................................................... 89 National Center for Complementary and Alternative Medicine.................................................. 90 Additional Web Resources ........................................................................................................... 95 General References ..................................................................................................................... 101 CHAPTER 4. CLINICAL TRIALS AND LIVER DAMAGE ................................................................... 103 Overview.................................................................................................................................... 103 Recent Trials on Liver Damage.................................................................................................. 103 Keeping Current on Clinical Trials ........................................................................................... 104 CHAPTER 5. PATENTS ON LIVER DAMAGE ................................................................................... 107 Overview.................................................................................................................................... 107 Patents on Liver Damage........................................................................................................... 107 Patent Applications on Liver Damage ....................................................................................... 113 Keeping Current ........................................................................................................................ 118 CHAPTER 6. BOOKS ON LIVER DAMAGE ....................................................................................... 121 Overview.................................................................................................................................... 121 Book Summaries: Federal Agencies............................................................................................ 121 Chapters on Liver Damage......................................................................................................... 122 CHAPTER 7. MULTIMEDIA ON LIVER DAMAGE ............................................................................ 129 Overview.................................................................................................................................... 129 Video Recordings ....................................................................................................................... 129 Audio Recordings....................................................................................................................... 130 CHAPTER 8. PERIODICALS AND NEWS ON LIVER DAMAGE ......................................................... 133 Overview.................................................................................................................................... 133 News Services and Press Releases.............................................................................................. 133 Newsletter Articles .................................................................................................................... 135 Academic Periodicals covering Liver Damage ........................................................................... 137 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 139 Overview.................................................................................................................................... 139 U.S. Pharmacopeia..................................................................................................................... 139 Commercial Databases ............................................................................................................... 141 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 145 Overview.................................................................................................................................... 145 NIH Guidelines.......................................................................................................................... 145 NIH Databases........................................................................................................................... 147 Other Commercial Databases..................................................................................................... 149 APPENDIX B. PATIENT RESOURCES ............................................................................................... 151 Overview.................................................................................................................................... 151
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Patient Guideline Sources.......................................................................................................... 151 Finding Associations.................................................................................................................. 171 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 173 Overview.................................................................................................................................... 173 Preparation................................................................................................................................. 173 Finding a Local Medical Library................................................................................................ 173 Medical Libraries in the U.S. and Canada ................................................................................. 173 ONLINE GLOSSARIES................................................................................................................ 179 Online Dictionary Directories ................................................................................................... 179 LIVER DAMAGE DICTIONARY............................................................................................... 181 INDEX .............................................................................................................................................. 255
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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 damage 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 damage, 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 damage, 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 damage. 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 damage, 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 damage. 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 DAMAGE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on liver damage.
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 damage, 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 damage” (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: •
Drinking Habits as Cofactors of Risk for Alcohol Induced Liver Damage Source: Gut. 41(6): 845-850. December 1997. Contact: Available from BMJ Publishing Group. P.O. Box 590A, Kennebunkport, ME 04046. Summary: The Dionysos Study is a cohort study of the prevalence of chronic liver disease in the general population of 2 northern Italian communities. It included 6,917 subjects, aged 12 to 65 years (69 percent of the total population). This article reports on a part of the study in which the authors examine the relationship between daily alcohol intake, type of alcoholic beverage consumed, and drinking patterns and the presence of alcohol induced liver damage in an open population. The study included 6,534 subjects, free of virus related chronic liver disease, and participating in the first cross sectional
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part of the study. Each subject provided a medical history and underwent physical examination, evaluation of alcohol intake using an illustrated dietary questionnaire, and routine blood tests. More invasive diagnostic procedures were performed when indicated. Multivariate analysis showed that the risk threshold for developing either cirrhosis or noncirrhotic liver damage (NCLD) in both sexes was ingesting more than 30 grams alcohol per day. Using this definition, 1,349 individuals (21 percent of the population studied) were at risk. Of these, only 74 (5.5 percent of the individuals at risk) showed signs of liver damage. After 50 years of age, the cumulative risk of developing both NCLD and cirrhosis was significantly higher for those who regularly drank alcohol both with and without food than for those who drank only at mealtimes. The authors conclude that in an open population the risk threshold for developing cirrhosis and NCLD is 30 grams of ethanol per day, and this risk increases with increasing daily intake. A commentary article on this research is published in the same issue. •
Liver Damage in Pharmaceutical Industry Workers Source: Environmental Health. 50(4): 293-297. July-August 1995. Contact: Available from Heldref Publications. 1319 18th Street NW, Washington, DC 20036-1802. (202) 296-6267. Summary: This article reports on a study of liver damage in a group of workers at a pharmaceutical manufacturing company and who participated in the entire production cycle. Numerous substances, including iodo-chloro-oxyquinoline, erythromycin, disinfectants, small amounts of cortisones, and preserving agents (prevan and parabenzoates), were used in the manufacturing process. A control group comprised individuals who were not exposed to hepatotoxic substances. The investigation was designed to determine the risk of hepatotoxicity in the pharmaceutical industry, and a protocol was used that allowed for ease of screening. In the presence of a physician, all subjects completed a clinical history questionnaire. They all underwent a general clinical examination, and specific blood chemistry tests were performed. Certain liver indices that were correlated with cytotoxicity were significantly higher in the pharmaceutical workers than among the controls. The findings confirmed that there was a problem of hepatic involvement among workers in this sector and that the clinical-biohumoral screening protocol used in this study is valid for identifying subjects at risk of hepatotoxicity. 4 figures. 2 tables. 18 references. (AA-M).
Federally Funded Research on Liver Damage The U.S. Government supports a variety of research studies relating to liver damage. 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 damage. 2
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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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 damage. The following is typical of the type of information found when searching the CRISP database for liver damage: •
Project Title: ALCOHOL METABOLISM GENES IN TRANSGENIC MICE Principal Investigator & Institution: Felder, Michael R.; Professor of Biological Sciences; Biological Sciences; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2003; Project Start 01-APR-1998; Project End 29-FEB-2008 Summary: (provided by applicant): Alcohol-induced liver damage and disease is an important health problem At least three enzyme activities in liver are capable of converting ethanol to acetaldehyde, alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase Although CYP2E1 is inducible by chronic alcohol exposure, results using naturally occurring and induced ADH-deficient animals suggest class I ADH plays a major role in ethanol metabolism and class IV plays a significant role. Class I ADH is expressed at high levels in the liver of mammals A single gene, Adh1, encodes class I ADH in mice while three genes, ADH1A, ADH1B and ADH1C, encode class I polypeptides in humans The overall goals are to identify distal genomic dements that control the expression phenotype of members of the mouse Adh complex, and to genetically manipulate by gene copy-number the ratio of ADH1/CYP2E1 in liver to explore the role of this ratio in alcohol-induced liver damage Distal cis-linked sequence in a BAC clone will direct expression of Adh1 in liver and Adh4 in stomach No sequence directing liver expression of any human class I ADH gene is known. Genetic approaches will define the important distal control element(s) for the Adh1 gene, and construct and use mouse strains on a constant C57BL/6 background with varying ADH1/CYP2E1 ratios to explore the role of each in alcohol induced liver injury The specific aims are (1) experimentally delineate the location of the distal sequence(s) controlling expression of Adh1 in liver, intestine and adrenal using transgenic expression assays, (2) determine if chromatin alterations occur in the expressed Adh1 region, (3) generally define the cis-linked sequence that promotes Adh4 proper expression phenotype, (4) genetically construct mouse strains (a) having ADH1/CYP2E1 ratio varying 8- fold using available knockouts and transgenics, (b) overexpressing ADH in lung, testes, seminal vesicle, and epididiymis in the absence of ADH in liver (a "conditional knockout"), (c) harboring a human CYP2E1 BAC for overexpression, and (5) explore pathology promoted by ethanol in these genetic strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALCOHOL REDUCTION IN MEDICAL ILLNESSES:HCV AS PROTOTYPE Principal Investigator & Institution: Dawson, Neal V.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Alcohol use is discouraged or contraindicated for patients with a variety of medical illnesses. For many diseases directly caused by alcohol, the use of alcohol may be associated with recurrent symptoms shortly after its consumption, e.g., pancreatitis or gastritis, and the prohibition against alcohol is straightforward. However, for many chronic diseases, the use of alcohol is not associated with any short-term symptoms or sequelae. The course of these chronic
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Liver Damage
diseases (or their treatments) among non-abusing/nondependent patients can be adversely affected by even moderate alcohol use, e.g., chronic hepatitis, (nonalcoholic) cirrhosis, severe diabetes, or the use of the 'blood thinner', warfarin. Chronic Hepatitis C virus (HCV) infection is a prototypical example of a disease in which alcohol use tends to cause no symptoms. Even moderate chronic alcohol use can be associated with an increased likelihood of cirrhosis and liver cancer. HCV infection rates and prognosis are related to alcohol use in multiple ways. Alcohol use during HCV treatment is associated with a decreased likelihood of viral clearance. Long-term alcohol use may increase the proliferation of HCV and the associated liver damage even with moderate alcohol consumption. Greatly reducing or eliminating alcohol use may importantly enhance the prognoses of patients, even if they are not candidates for specific HCV treatments. Despite having diagnoses that warrant abstinence from alcohol, many patients continue to drink alcohol. Little is known about why patients continue to consume alcohol in the face of diagnoses that warrant a reduction in use or abstinence. The current study is designed to determine factors that lead to continuing alcohol intake among alcohol nonabusing/nondependent patients who are advised to stop drinking by health care providers. In Phase 1, focus groups (patients and providers) will be used to discover issues that may be associated with continued drinking. In Phase 2, questionnaire items will be developed based on the data gleaned from Phase 1. The potential pool of items will be administered to 10 patients per item and factor analyzed. In Phase 3, the items retained from the pool of potential items will be used to create a questionnaire that will be tested for its ability to predict alcohol reduction or cessation. Since alcohol use is common in the U.S. and since most patients who currently have HCV are not candidates for treatment, abstinence from alcohol use represents a major opportunity to prevent a decline in the health and quality of life of patients with HCV and similar diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL, INOS UPREGULATION, LEAKY GUT & LIVER DISEASE Principal Investigator & Institution: Keshavarzian, Ali; Professor of Pharmacology & Molecular Bi; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Clinically significant alcoholic (A) liver damage (LD), secondary to a hepatic necroinflammatory cascade (HNIC), occurs only in a subset of alcoholics. Hence, factors other than ethanol (E) must be involved. Hypothesis: The key cofactor for ALD is a breakdown of gut barrier integrity ("leaky gut") due to chronic E use, which allows intestinal endotoxin to reach the liver & initiate a HNIC; this leakiness is due to cytoskeletal instability caused by oxidation of cytoskeletal proteins which is elicited by E-induced gut iNOS upregulation & nitric oxide (NO) overproduction. We found: 1} in man, gut leakiness in alcoholics with LD but not in those without LD or in nonalcoholics with LD; 2} in rats, E-induced leaky gut is associated with LD; reversal of gut leakiness attenuates LD; 3} in intestinal monolayers, E-induced iNOS upregulation causes cytoskeletal & barrier disruption. We will continue to use this successful translational approach (monolayers, rats & man) to test our current hypotheses. Aims: (1) To see if, in a larger sample, a leaky gut: a) occurs only in alcoholics with LD & precedes cirrhosis b) persists during abstinence & after liver transplant for ALD, c) correlates quantitatively with LD severity, d) is associated with NO overproduction & HNIC, e) is more pronounced in females. We predict that gut leakiness (excess urinary lactulose, mannitol & sucralose levels after oral sugar load): i) is seen only in alcoholics with LD, precedes cirrhosis; ii) correlates with severity of LD (clinical parameters, liver enzymes); iii) is associated with NO overproduction (gut
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mucosal NO), serum endotoxin & HNIC (high neopterin/cytokines). (2) To see if, in rats, prevention of E-induced leaky gut also prevents E-induced LD & if a hyperactive, NO pathway is involved. We predict that in E-fed rats with LD: i) leaky gut, endotoxemia, HNIC, upregulation of intestinal iNOS, NO overproduction & oxidation of actin & tubulin occurs; ii) preventing gut leakiness (by oats, iNOS inhibitors or Arginine) prevents LD. (3) To see, using monolayers of wild type ((inhibitors) & transfected cells, if E-induced iNOS upregulation & its consequences (assessed by cytoskeletal oxidation/disarray & barrier disruption) are mediated by NF-kappaB activation. We predict i) E activates NF-kappaB by degrading IkappaBalpha; ii) preventing NF-kappaB activation prevents E-induced iNOS upregulation & its consequences. Significance: Showing that ALD requires a leaky gut, & that NO & cytoskeletal pathways are involved, could 1) identify drinkers at risk for LD (sugar test); 2) lead to therapies to prevent LD in those drinkers unable to abstain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL/CELLULAR IMMUNITY IN HCV AND HIV INFECTION Principal Investigator & Institution: Chang, Kyong-Mi M.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 28-SEP-2000; Project End 31-JUL-2005 Summary: Up to 3% of the world population is infected with hepatitis C virus (HCV), a hepatotropic RNA virus that causes acute and chronic hepatitis as well as cirrhosis and hepatocellular carcinoma. HCV infection results in chronicity in most cases (85%) despite detectable antiviral immune response, and recent studies suggest that virusspecific T cells play an important role in the outcome of HCV infection. Interestingly, HCV infection is up to 7 fold more prevalent in alcoholic individuals than in the general population, and chronic alcohol use in HCV-infected patients is associated with accelerated liver disease progression and development of liver cancer. While alcohol is known to suppress cellular immune response, little is known about the effect of alcohol on HCV-specific T cell response in HCV-infected patients. Therefore, the primary aim of this application is to determine if chronic alcohol use results in a pathogenetic HCVspecific T cell response that promotes further liver damage than virus control. In addition, we will determine the extent to which this may be reversed upon alcohol cessation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIGEN-INDEPENDENT CD8 T CELL-INDUCED HEPATITIS Principal Investigator & Institution: Pierce, Robert H.; Pathology and Lab Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): This proposal outlines a career development program with the goal of developing a successful academic career in Pathology. The principal investigator (PI) is an Assistant Professor with a tenuretrack appointment in Pathology at the University of Rochester School of Medicine (UR). He is a diplomat of the American Board of Pathology and possesses significant clinical and teaching experience. This Mentored Clinical Scientist Award (KO8) proposal will facilitate the acquisition of basic research expertise in the area of liver immuno- pathology through a 5 year educational and research program focusing on the mechanism of antigenindependent CD8 T cell -induced liver damage. The liver appears to play a unique role in the elimination of CD8 T lymphocytes undergoing activation-induced apoptosis. Our
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current understanding of this mechanism of T cell clearance is based largely on the work of Dr. Crispe, the PI's Mentor, using mouse models expressing transgenic T cell receptors (TCR). Binding of target peptide to these transgenic T cells causes a clonal expansion, resulting in their selective uptake by the liver and subsequent death. As a consequence of this ongoing lymphocyte apoptosis in the liver, serum transaminase levels increase, indicating hepatocyte injury in the absence of hepatocyte expression of target antigen. Recent work in the PI's laboratory has demonstrated hepatitis, consisting of cellular infiltrates containing both CD8 T celland Kupffer cells both in the transgenic TCR model as well as in influenza infection. These data suggest that this phenomenon may represent a general response to expanded CD8 T cell populations and a common pathway of liver injury, which may have significant clinical implications. This study will investigate the mechanism of this novel antigen-independent CD8 T cell-induced hepatitis. Dr. Crispe is one of the leaders in the emerging area of liver-specific immunobiology and has an excellent track record as a mentor. In addition, a career development advisory committee consisting of 3 additional senior scientists will provide advice and guidance to the PI. Overall, the UR provides an outstanding setting by providing both excellent facilities and by fostering an atmosphere of support and collaboration. This structured and mentored program will facilitate the PI's evolution to independence as an investigator, culminating in a future RO1 application in the area of liver immunopathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOENERGETICS PATHOGENESIS
AND
ALCOHOLIC
LIVER
DISEASE
Principal Investigator & Institution: Diehl, Anna M.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: (Adapted from the Investigator's Abstract): Chronic ethyl alcohol (EtOH) consumption causes fatty liver (steatosis), but does not usually result in cirrhosis unless fatty liver hepatitis (steatohepatitis) develops. Thus, the transition from steatosis to steatohepatitis may be a rate-limiting step in the evolution of cirrhosis. Factors that induce TNFalpha or enhance hepatocyte vulnerability to its lethality potentiate progression to steatohepatitis. However, the mechanisms involved are not understood. Obesity is a risk factor for EtOH-related cirrhosis and, even in non-drinkers, is often associated with fatty liver. There are similarities between genetically obese, ob/ob mice with fatty livers and mice EtOH-induced fatty livers-both develop severe liver damage when challenged by small amounts of endotoxin or transient hypoxia. The investigator's preliminary data suggest that obesity actually potentiates the hepatotoxicity of EtOH because, unlike lean mice, ob/ob mice develop steatohepatitis when drinking EtOH chronically. Thus, the ob/ob mouse is a novel small animal model that can be used to characterize mechanisms that mediate the transition from steatosis to steatohepatitis. The purpose of this project is to use this model to evaluate the individual, and combined, effects of obesity and Et-OH-exposure on hepatic mitochondria. Mitochondria regulate cell viability by controlling ATP production and the release of noxious substances, including reactive oxygen species and pro-apoptotic factors. The mitochondrial uncoupling protein, UCP2, limits both ATP and ROS production during mitochondrial respiration and, thus, might modulate susceptibility to necrosis and/or apoptosis. The investigators have new evidence that obesity, and other factors that potentiate EtOH-related hepatotoxicity, up-regulate the expression of UCP2 in hepatocytes. This project will evaluate the HYPOTHESIS that hepatocytes that have
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already adapted to obesity by up-regulating UCP2 are particularly prone to develop lethal mitochondrial dysfunction when exposed to EtOH. Pair feeding studies in ob/ob and learn mice and experiments in cultured hepatocytes will address three Specific Aims: 1) to characterize the effects of EtOH, obesity, and EtOH + obesity on hepatic UCP2 expression, vital mitochondrial parameters (e.g., glutathione levels, cytochrome c release, ROS and ATP production), and liver damage; 2) to determine if UCP2 induction potentiates mitochondrial membrane depolarization by EtOH or other factors (e.g., TNFalpha) that promote EtOH-hepatotoxicity; and 3) to determine if increased ROS production induces UCP2 and, thus, if inhibiting ROS by antioxidant therapy will prevent UCP2 induction, mitochondrial dysfunction, and liver damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHANGES IN CA2+ DEPENDENT SIGNAL TRANSDUCTION AFTER CHRONIC ALCOHOL EXPOSURE Principal Investigator & Institution: Hoek, Joannes B.; Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002 Summary: Chronic alcohol treatment is associated with alterations in the regulation of specific steps in the complex network of intracellular signal transduction processes that are triggered by the activation of receptors in the plasma membrane. This proposal is focused on G protein-coupled signaling processes in the liver that are mediated by phosphoinositide- specific phospholipase C and that result in the activation of protein kinase C and the elevation of cytosolic free Ca2+ concentrations ([Ca2+]i). Previous studies from our laboratory identified multiple steps that are affected by chronic ethanol intake. One of the sites affected is the inositol 1,4,5-trisphosphate (InsP3) receptor that mediates Ca2+ release from intracellular Ca2+ stores. Another site involves the feedback desensitization mechanisms that control receptor activation of phospholipase C. This feedback process appears to be involved in the development of tolerance to the effects of acute ethanol treatment, which inhibits this signaling system. One specific aim is devoted to the analysis of the control of the InsP3 receptor by Cab and other divalent cations. We will study the InsP3 binding to the receptor and opening of the receptor cation channel and determine ligand induced InsP3 receptor desensitization. We will also analyze the role of immunophilins and receptor phosphorylation in the changes in InsP3 receptor function induced by chronic ethanol feeding. Additionally, we will determine if chronic ethanol treatment causes changes in the endoplasmic reticular Ca2+ pump activity and the Ca2+ leak pathway and assess the contribution of mitochondrial Ca2+ fluxes to the activity of the InsP3 receptor. The second specific aim is designed to analyze the consequences of the changes in Ca2+ signaling responses for the integration of liver metabolism. We have found that changes occur in the patterns by which hormonally-induced translobular Ca2+ waves occur at low concentrations of vasopressin or other hormones. We plan to analyze the mechanistic basis of the changes in Ca2+ waves across the liver lobule and determine to what extent intercellular transfer of Ca2+ signals is a consequence of the altered cellular response after chronic ethanol feeding or involves changes in cell-cell interaction thrOugh gap junctions. We will also investigate the consequences of altered translobular Ca2+ signaling patterns for bile secretion in chronic alcoholism. Finally, we will determine if the changes in Ca2+ signaling patterns affect mitochondrial Ca2+-dependent oxidative metabolism in a heterogeneous manner across the liver lobule. Changes in hormone-induced translobular Ca2+ signaling may contribute to the liver damage associated with chronic alcohol intake.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIETARY RESTRICTION INFLAMMATORY RESPONSE
AND
ATTENUATION
OF
Principal Investigator & Institution: Nolan, Colleen J.; St. Mary's University 1 Camino Santa Maria San Antonio, Tx 78284 Timing: Fiscal Year 2002 Summary: Dietary restriction (DR) has been demonstrated to prolong the lifespan of a number of organisms. Fischer 344 rats demonstrate a two-fold increase in plasma corticosterone (B) in response to DR which is maintained during the life span of the animal. This increase in B is related to physiological changes associated with life extension: decreased cell division, alterations in other hormones associated with nutrient allocation and endocrine regulation, and a attenuation of the inflammatory response. Together these physiological changes may be indicators of the role of B as a mediator of the ability of DR to prolong life span. The objective of this pilot proposal is to test the hypothesis that the mechanism by which DR attenuates inflammation through elevated B is to alter the secretion of B and the expression of specific genes involved in the inflammatory process. This hypothesis will be tested using the male Fischer 344 rats, an animal model commonly used in aging studies. The specific aim of this pilot project is to examine the time course of the inflammatory response in young ad libitum fed (AL) and DR rats in response to lipopolysaccharide (LPS; an inflammatory agent). The response to LPS will be measured by examining the LPS-induced rise in adrenocorticotropin (ACTH) and in the plasma. Additionally, the ability of LPS to induce the expression of genes known to be involved in the inflammatory response (inducible nitric oxide synthase and cytokines) and liver damage (as indicated by the presence of specific hepatic enzymes) will be measured. It is hypothesized that if DR does indeed prolong life span by suppressing the immune response and/or by altering the sensitivity of animals to an inflammatory agent, then the LPS-induced rises in ACTH and B, expression of genes involved in the inflammatory response and the concentration of liver specific enzymes will be decreased in DR compared to AL rats. This pilot project will provide the foundation research necessary to further explore one particular aspect through which DR prolongs provide the foundational research necessary to further explore one particular aspect through which DR prolongs life span, the role of the hypothalamic-hypophyseal-adrenal axis (HPA) in mediating the response to inflammatory challenge. If such a role is indeed elucidate, then it would add further support to the theory that dietary induced hypercorticosteronism is a key mediator of life extension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIPHTHERIA FUSION PROTEIN THERAPY OF AML Principal Investigator & Institution: Frankel, Arthur E.; Professor of Cancer Biology and Medicine; Cancer Biology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 12-DEC-1997; Project End 31-DEC-2006 Summary: Ten thousand people in the U.S. develop acute myeloid leukemia (AML) each year. While many patients achieve remissions with combination chemotherapy, most relapse and die with drug resistant disease. We have produced a diphtheria fusion protein (DT388GMCSF) consisting of the catalytic and translocation domains of diphtheria toxin fused to human granulocyte-macrophage colony- stimulating factor.
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We initiated a phase I single-arm, inter-patient dose escalation clinical trial of five daily intravenous infusions for patients with relapsed or refractory AML. To date, we have observed dose- related transient elevations in liver enzymes and circulating inflammatory cytokines. Half of the patients were found to have pre- treatment antibodies to DT388GMCSF >2mu g/mL associated with reductions in the peak blood concentrations of DT388GMCSF. Clinical remissions have been observed at the higher dose levels. In the next funding period, we propose to better define the potential role for DT388GMCSF in the care of AML patients. We will complete the on- going phase I study and expand the cohort of patients at the maximal tolerated dose to better estimate the preliminary response rate and side effects. Further, we propose three areas of laboratory studies to be carried out to facilitate our understanding of the molecular pharmacology of DT388GMCSF in these patients. In Specific Aim 1, the molecular mechanism for the liver damage and cytokine release will be investigated. The amount and types of cytokines released into the blood will be measured. Patient cytokine gene polymorphisms will be determined. A rat model will be used to determine whether the cytokines induce the liver injury. Methods of prevention of the cytokine release and liver injury in the rat will be tested. If successful, such measures may be tested in patients. In Specific Aim 2, anti- DT388GMCSF antibody formation and DT388GMCSF serum levels will continue to be measured and correlated with toxicity and response. In Specific Aim 3, pre-treatment blast proliferation sensitivity to DT388GMCSF will be measured and correlated with clinical response. These studies should lead to the design of pivotal phase II clinical trials to determine the role of this therapeutic in AML management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EDG ACTIVATION
RECEPTOR
SIGNALING
IN
HEPATIC
STEM
CELL
Principal Investigator & Institution: Svetlov, Stansilav I.; Pathology, Immunol & Lab Med; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Proliferation and differentiation of hepatic oval (stem) cells are regulated by a variety of factors, yet not completely understood. Lysophosphatidic acid (LPA) and sphingosine-l-phosphate (S1P) are {phospholipid growth factors}, which regulate cell proliferation and differentiation, increase motility, and even enhance survival in several cell types. Cellular effects of LPA and S1P are mediated mainly via G-protein coupled receptors encoded by Endothelial Differentiation Genes (EDG). We have found that induction of oval cell proliferation during liver damage was associated with the expression of several types of EDG receptors, predominantly in small oval cells. We, therefore, hypothesize that the EDG expression profiles and the corresponding cellular responses to EDG receptor ligands LPA and S1P are specific for hepatic stem cells at various stages of differentiation {to mature hepatocytes/cholangiocytes}. Moreover, we propose that differential expression of EDG receptors may be a necessary part of the mechanism responsible for the activation of hepatic stem cells. The goals of this project are to explore hepatic EDG receptor profiles {during liver injury in vivo}, and {determine oval cell responses and EDG-mediated signaling by LPA/S1P in vitro}. These goals will be achieved by pursuing two Specific Aims: (1) to characterize the pattern of hepatic EDG receptors at different stages of mouse chronic liver injury accompanied by proliferation of hepatic oval cells; and (2) To identify how EDG-mediated cell signaling by LPA/S1P will regulate hepatic oval cell activation, proliferation and differentiation in culture. The
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Liver Damage
results will establish the expression profiles and localization of EDG receptors during hepatic oval cell proliferation and differentiation, and will determine intracellular signaling pathways of oval cell activation by LPA/S1P. Successful accomplishment of the project will provide novel information exploring lipid mediator signaling in stem cells, which will have a great value to develop new insights in stem cell biology. Finally, we believe that the data produced in the field of lipid signaling mechanisms during proliferation and differentiation of stem cells can be used to generate an R01, which will further expand our understanding of stem cell biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF HEPATOTOXINS & ADOMET ON LIVER GENE EXPRESSION Principal Investigator & Institution: Kruger, Warren D.; Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Chronic liver disease such as cirrhosis, hepatitis, fibrosis, and fatty liver, is associated with reduced levels of S-Adenosylmethionine (AdoMet) in the liver. AdoMct affects a variety of metabolic pathways including methylation, anti-oxidant defense and polyamine production. Evidence from a variety of model systems suggest that dietary supplementation with AdoMet can attenuate liver damage and improve liver function. Despite these intriguing observations, little is known about the effect of AdoMet supplementation at the molecular level. In this R21 exploratory proposal we will examine the effects of AdoMet supplementation at the level of gene expression on a global scale using a rodent model. We will test the hypothesis that hepatotoxins, such as alcohol, have discreet effects on gene expression and that AdoMet supplementation can reverse at least some of these effects. Our experimental approach will use Wistar rats that are assigned to one of six groups: untreated AdoMet treated, alcohol treated, alcohol+AdoMet treated, CCI_ treated, and CC14+AdoMet treated. Using DNA microarrays we will compare global gene expression patterns in each of these groups and determine what! genes and biological pathways are affected by various hepatotoxins and AdoMet supplementation. In addition, we will measure various AdoMet metabolites in the liver to determine the effect of these treatments on AdoMet metabolism. From these studies we will determine how liver hepatotoxins and AdoMet affect gene expression profiles. This information should be informative as to what types of biological pathways are perturbed by these treatments. This knowledge will be useful in understanding the molecular changes that characterized liver disease and the molecular basis for clinical improvement with AdoMet in liver disease. This work may also be useful in the identification of biological pathways affected in chronic liver disease that are not affected by AdoMet supplementation, which may represent other correctable targets in chronic liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF POLYUNSATURATED LECITHIN ON LIVER FIBROSIS Principal Investigator & Institution: Schenker, Steven; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002 Summary: This is a multicenter, placebo-controlled, parallel study of polyunsaturated lecithin on the progression of fibrosis to cirrhosis in patients with alcoholic liver damage. Its objective is to evaluate the preventive effect of polyunsaturated lecithin and
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to assess the corresponding changes in hepatic collagen measured directly (by liver biopsy) and indirectly (by propeptide changes in the blood). The effect of lecithin on histologic parameters of steatosis, inflammation, and necrosis will also be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENZYME DEFECTS IN DISORDERS OF PROTOPORPHYRIN METABOLISM Principal Investigator & Institution: Bloomer, Joseph R.; Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-JUL-1979; Project End 31-MAY-2006 Summary: (provided by applicant): Protoporphyria (EPP) is a genetic disorder in which deficient activity of the mitochondrial enzyme ferrochelatase (FECH) causes excessive accumulation of protoporphyrin. As a consequence patients have photosensitivity which is variable in degree, and some develop liver disease. Molecular studies from this and other laboratories have shown that most patients are heterozygous for FECH gene mutations which do not explain the phenotypic variation. The major objective of this proposal is to examine the hypothesis that the level of expression of the FECH allele which encodes normal protein (nonmutant allele), is also a critical factor. In the first specific aim families in which members have different phenotypic expression of EPP will be studied to determine whether inheritance of a low-expressing nonmutant FECH "allele, together with the mutant FECH allele, has occurred in those with symptomatic EPP. Haplotype analysis will distinguish mutant from nonmutant alleles, and the level of normal FECH mRNA will be specifically assessed in cultured lymphoblasts. The presence of an intron polymorphism associated with aberrantly spliced FECH mRNA that is rapidly degraded will be examined for in the nonmutant allele. The promoter region and more extended 5'- untranslated region of the nonmutant FECH allele will also be sequenced and expressed in an in vitro system. In the second specific aim, a mouse model of EPP in which there is a heterozygous deletion of exon 10 will be backcrossed with inbred strains of mice which are selected for different levels of FECH gene expression on the basis of FECH activity and FECH mRNA levels in liver and bone marrow. It is anticipated that the level of FECH activity, and hence degree of protoporphyrin accumulation, will vary in heterozygous offspring according to the level of FECH gene expression in the wild-type parent. Liver and bone marrow will be assessed for FECH activity, FECH mRNA, and levels of normal and mutant FECH proteins. Liver mitochondria will be examined for the presence of heterodimers consisting of the normal and mutant FECH proteins. Phenotype will be assessed by the protoporphyrin levels, and degree of photosensitivity and liver damage. The proposal thus is designed to define a critical relationship between FECH gene expression and phenotype in EPP which will lead to better genetic counseling and therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY OF HEPATOCELLULAR HEPATITIS B VIRUS IN 3 POPULATIONS
CARCINOMA
&
Principal Investigator & Institution: London, W T.; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002 Summary: (Applicant's Description) Prospective studies of 60,984 men in Haimen City, China and 19,469 men in Senegal, west Africa revealed a 14-fold greater death rate from hepatocellular carcinoma (HCC) among the Haimen (168 per 100,000) than the
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Liver Damage
Senegalese cohort (12 per 100,000). Even though chronic infection with hepatitis B virus (HBV) is the major risk factor for HCC in both populations, the age-adjusted prevalence of chronic infection is about 20% in both cohorts. Exposure to aflatoxin, a postulated major risk factor for HCC, is also similar or greater in the Senegalese population. The prevalence of viremia (HBV DNA in serum) among HBV carriers throughout adult life, however, is much higher among the Chinese than the Senegalese population. Nevertheless, within the Chinese cohort, viremia at study entry is not a risk factor for HCC after four years of follow-up. The aims of this project focus on factors that may account for variation in HCC risk in the Chinese and Senegalese cohorts and a cohort of Asian-American HBV carriers living in the Philadelphia area. Continued tracking of these three cohorts will test the hypothesis that with longer duration of follow-up, H B V v iremia and liver damage at study entry are associated with person-specific risks of HCC and that aflatoxin-B1 (AFB1)-albumin adducts are a s s ociated with development of HCC among viremic individuals and/or genotypically determined poor detoxifiers of AFB1 (in collaboration with Project 2). In close cooperation with the studies of WHV in woodchucks (Project 3), an intensive longitudinal study of 1000 male and female HBV carriers in these three populations will be conducted to: a) examine whether perturbations of the stability of HBV serum markers are associated with acute illnesses, aflatoxin exposure, and/or outgrowth of viral mutants; b) assay hepatocyte turnover and immune responses in liver biopsies; c) correlate these measures with viral load; d) examine the relationship of sex differences in changes in HBV serum markers over time to the lower HCC risk of female HBV carriers. Because present studies show that an episode of acute hepatitis in adulthood approximately doubles HCC risk among both HBV carriers and non-carriers, the causes and outcomes of 200 cases of acute hepatitis in Haimen City will be characterized. This research will lead to a new level of understanding of the factors that lead to HCC and to new strategies for the prevention of this lethal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL EFFECTS ON LIVER IN SELF-ADMINISTERING PRIMATES Principal Investigator & Institution: Cunningham, Carol C.; Professor; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Most protocols that employ animal models for studying the development of alcoholic liver disease utilize the rat that is being administered ethanol as part of the diet. These models have provided much of the information we presently have on the mechanisms that contribute to development of liver damage associated with alcohol abuse. To date there are no animal models where voluntary ethanol consumption has led to irreversible liver damage; i.e., damage past the fatty liver stage. The studies proposed in this application are designed to determine if non-human primates that are self-administering ethanol will demonstrate liver pathology predictive of the development of alcoholic hepatitis and fibrosis. Eleven Macaca fascicularis monkeys will be given free access to ethanol in drinking water for 1 year. These animals have been previously trained to drink ethanol voluntarily and some have consumed up to 4g/kg/day, which is equivalent to 16 drinks a day by a human. The heavier drinkers averaged blood ethanol concentrations of 170 mg/dl in a previous protocol. In the proposed studies, light, moderate and heavy drinkers will be included, which are comprised of 6 females and 5 males. Evidence for liver damage will be sought by analyses of blood samples, which will include measurements of y-
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glutamyltransferase, aspartate and alanine transaminases, bilirubin, albumin, globulin and other blood components. Urinary concentrations of isoprostanes will be measured to screen for ethanol-related oxidative stress. Liver needle biopsy samples, taken every 3 months, will be examined by light and electron microscopy for indices of liver damage, such as hepatocyte ballooning, Mallory body formation, inflammation and fibrosis. lmmunohistochemical analyses will be implemented to measure levels of inflammation, apoptosis and stellate cell activation. The objectives of this study are 1) to determine if the self-administering M. fascicularis will develop liver pathology past the fatty liver stage and 2) to evaluate the efficacy of using blood and urine samples to follow development of alcoholic liver disease in an animal model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXTREME AMMONIA TOLERANCE MECHANISMS: A MODEL VERTEBRATE Principal Investigator & Institution: Walsh, Patrick J.; Marine Biology and Fisheries; University of Miami Coral Gables Box 248293 Coral Gables, Fl 33134 Timing: Fiscal Year 2002; Project Start 08-FEB-2002; Project End 30-NOV-2004 Summary: (provided by applicant): Hepatic Encephalopathy (HE), and resultant elevated blood and tissue ammonia concentrations (i.e., hyperammonemia, HA), has profound central nervous system (CNS) effects, and can have environmental causes. In particular, liver damage due to exposure to toxicants such as carbon tetrachloride, toluene, DDT, heptachlor, etc., as well as chronic alcoholism and direct exposure to environmental ammonia, can elicit symptoms of HE/HA. However, there are such a wide variety of CNS effects produced in the disease in humans, and in rodent experimental models, that it is difficult to determine which disease biomarkers are the most critical indicators of disease progression. Furthermore, characteristics of the rodent model present several weaknesses in the study of HE/HA. Because of this gap in our knowledge, no practical and effective clinical intervention strategies are available to prevent or reverse biomarkers or symptoms of the disease. Recently, we have identified a vertebrate model, the gulf toadfish (Opsanus beta), which is both extremely tolerant of ammonia insult, and which, by virtue of its aquatic lifestyle, enables a line of experimentation not practical in mammalian models, namely rapid "ammonia washout" protocols. Therefore, we propose to test several hypotheses aimed at exploiting these and other characteristics of this new model to address the lack of biomarkers and intervention strategies for HE/HA. In particular, we will: (1) test the hypothesis that there are reversible vs. irreversible biomarkers of HE/HA, and that these can be readily identified and distinguished in an aquatic model like the toadfish; (2) test the hypotheses that extreme ammonia tolerance in the toadfish, relative to mammals, is due to an unusual aspect of its physiology, in particular, either to a more robust ammonia detoxification system in the brain, or to an inherent insensitivity of brain mitochondrial metabolism to ammonia insult. As a further test of this second hypothesis, we will also explore the possibility that the toadfish has higher levels of naturally occurring ammonia protectant compounds (e.g., carnitine, trimethylamine oxide, etc.) in its brain tissues than do mammals. In sum, these experiments will lead to information which is not readily obtainable from humans and existing mammalian models concerning the mechanisms of action of ammonia and cellular capacity for tolerance and recovery, and thus to a better understanding of the causes and mechanisms underlying HE/HA that could lead to therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAS/FASL INTERACTION IN LIVER DAMAGE Principal Investigator & Institution: Hahn, Young S.; Assistant Professor; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Hepatitis C virus (HCV) infection in humans is remarkably efficient in the establishment of persistent infection by evading host immune surveillance. HCV persistent infection is a major risk factor for the development of hepatocellular carcinoma and autoimmune disease. In our prior studies, we demonstrated that HCV core protein, a first protein produced during viral infection contains the immunomodulatory function to suppress anti-viral CTL activity through its interaction with Fas to increase the Fas-mediated apoptotic pathway. To dissect the molecular mechanism of immune modulation by HCV core and immunopathogenesis of liver damage, we have developed a murine model of CD2/core transgenic mice by directing the expression of HCV core protein in T cells because T cells support HCV infection and replication of virus. In these CD2/core transgenic mice, similar to chronic hepatitis C in humans, massive lymphocytic infiltration was notable in the portal tract of liver along with profound immune dysregulation. In addition, the expression of core protein in OVA-specific CD4+ T cells induces severe liver damage by facilitating recruitment of lymphocytes to liver in core-TCR mice upon OVA323-339 peptide injection. Based on these findings, we hypothesize that FasL of liver-infiltrating T cells may be responsible for inducing liver damage as a bystander killing mechanism by promoting FasL-mediated pro-apoptotic and inflammatory responses. In order to test this hypothesis and further investigate the molecular mechanism of hepatocyte damage by liver-infiltrating T cells, we will first explore the mechanism of hepatocyte damage by liver-infiltrating T lymphocytes. Secondly, we will characterize the status of T cell activation and differentiation of liver-infiltrating T cells in core-TCR mice. Lastly, we will analyze the regulation of hepatocyte inflammatory activation by liver-infiltrating T cells. The studies proposed here will provide new and useful information on the pathogenesis of liver damage by Fas/FasL-induced inflammatory response and will help to provide a basis for the rational design of novel therapeutic agents to liver damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC MODELS TO STUDY ALCOHOL TOXICITY Principal Investigator & Institution: Vasiliou, Vasilis; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The long-term goal of this project is to understand the role of CYP2E1, ALDH2, and ALDH1 genes which encode alcohol-metabolizing enzymes, in alcoholinduced oxidative stress and toxicity. Chronic alcohol abuse results in a variety of pathological effects, including liver fibrosis and cirrhosis. Some of the toxic effects of ethanol have now been linked to ethanol metabolism. Ethanol consumption causes a CYP2E1 induction, which is associated with increased levels of acetaldehyde, generation of reactive oxygen species (ROS), lipid peroxidation, mitochondrial GSH depletion, and increased collagen synthesis. Most of the toxic effects of ethanol are due to acetaldehyde and potential molecular targets include proteins, lipids and mitochondrial DNA. Genetic polymorphisms exist in human CYP2E1 and ALDH2 genes that may influence the risk for developing alcoholic liver disease. Interestingly, chronic ethanol
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consumption mimics the oxidative stress seen in aging animals, particularly in liver. Although the importance of oxidative stress in cellular damage is well appreciated, the molecular mechanisms by which alcohol induces oxidative stress and causes liver damage are still unknown. Our hypothesis predicts that chronic alcohol consumption induces oxidative stress and cellular injury that is associated with imbalances in the production/detoxification of intermediates (acetaldehyde) or reactants (ROS and lipid peroxidative products) of ethanol metabolism. To test this hypothesis, the role of Cyp2e1, Aldh2 and Aldh1 genes in ethanol metabolism and liver in injury will be investigated by using transgenic mouse lines having homozygous disruptions in these genes. For the 5-year period of this grant application, we therefore propose to: Specific Aim 1: Develop conventional, as well as inducible, Aldh2 and Aldh1 knockout transgenic mouse lines; Specific Aim 2: Use the Aldh2, Aldh1 and a Cyp2e1 knockout mouse lines to study the role of these genes in ethanol/acetaldehyde pharmacokinetics and metabolism; Specific Aim 3: Use the Cyp2e1 Aldh2 and Aldh1 knockout mouse lines to test the hypothesis that CYP2E1 (involved in ROS production), ALDH2 and ALDH1 I (involved in acetaldehyde detoxification) are involved in the alcohol-induced oxidative stress that leads to liver injury. Liver injury will be studied in parallel with: i) oxidative stress, ii) assessment of lipid peroxidation, iii) characterization of molecular targets of oxidative stress-mediated injury including mitochondrial DNA damage and genes involved in collagen synthesis and degradation. These studies will greatly enhance our understanding of genetic factors involved in alcohol toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HCV INFECTION--RISK FACTORS FOR PROGRESSION Principal Investigator & Institution: Stuver, Sherri O.; Assistant Professor; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): For individuals who are infected with hepatitis C virus (HCV), knowledge of co-factors affecting the occurrence of liver disease is crucial. However, the mechanisms of HCV-associated pathogenesis, particularly with regard to the role of the virus and the host immune response, remain unclear. The primary goal of the proposal is to elucidate the natural history of HCV infection with respect to progression to hepatocellular carcinoma (HCC) and other health outcomes in a Japanese community-based population in which infection with HCV is highly endemic. As part of an annual ultrasonographic tomography screening program in this population, nearly 1,000 adult residents with HCV have been under surveillance for liver cancer since 1994. The proposed study will extend the observation of this cohort, with the additional collection and analysis of virologic, epidemiologic, and clinical data. The specific aims of the research are: to determine the predictive value of markers of HCV infection in the development of liver damage and HCC; to estimate the effect of host-related factors, including heavy alcohol consumption, cigarette smoking, and diet, on HCV-induced liver disease progression and hepatocarcinogenesis; to examine the role of co-infection with hepatitis B virus and human T-lymphotropic virus type I in the natural history of HCV; to characterize the function of host immune status and response in the persistence of HCV infection as well as in the progression of liver disease and HCC among HCV carriers; to evaluate the utility of serologic markers of liver damage in predicting the development of HCC in individuals infected with HCV; to identify predictors of extrahepatic morbidity and mortality among HCV carriers. The uniqueness of the study population and the richness of the data parameters combined with the extensive
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experience of the assembled multi-disciplinary team provide an important opportunity to increase our understanding of the natural history of HCV and to contribute to our ability to identify and potentially treat those carriers who are at increased risk of an adverse outcome related to their HCV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATITIS C VIRUS NS5A PROTEIN AND PATHOGENESIS Principal Investigator & Institution: Ray, Ratna B.; Pathology; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Hepatitis C virus (HCV) often causes a prolonged and persistent infection. Association between hepatocellular carcinoma (HCC) and HCV infection has been noted. Immune evasion and quasi-species nature are prominent features of HCV. Understanding the molecular basis of viral pathogenesis is a major challenge to gain insight into HCV associated disease progression. The pathogenesis of liver damage is likely to be related to both viral and immune mediated factors. Recent experimental evidence using HCV cloned genomic regions suggests that the NS5A protein has many intriguing properties. These include the presence of an interferon sensitivity determining region (ISDR), direct repression of PKR, a regulatory role on important cellular promoters, and promotion of cellular transformation. Together these observations provide a compelling reason to focus and design studies to further our understanding of the molecular mechanism and cellular targets of HCV NS5A protein mediated biological functions. Available information suggests that during persistent infection NS5A protein may play a critical role in concert with cellular factors for virus mediated pathogenesis. This research proposal is designed to (1) Determine the role of HCV NS5A protein on cell cycle regulatory genes and map the transregulatory domain; (2) Investigation the interaction of HCV NS5A protein with cellular target protein(s); (3) Determine the role of HCV NS5A protein in cytokine mediated apoptosis; (4) Determine the transforming potential of HCV NS5A protein in primary human hepatocytes; and (5) Determine whether HCV NS5A protein expression promotes liver pathogenesis in transgenic mice. Results from this study will lead to a better understanding of the virus mediated pathogenesis. The long term goal of this study is to design effective strategies for the intervention of HCV mediated disease in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPATITIS C VIRUS, ALCOHOL AND HOST DEFENSE Principal Investigator & Institution: Szabo, Gyongyi; Associate Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Alcohol use accelerates the progression of liver disease in chronic hepatitis C (HCV) infection; however, the interactions between alcohol and HCV have not yet been explored. Chronic HCV infection is associated with reduced HCV-specific immune responses, and alcohol use suppresses antigen-specific T cell activation via inhibition of monocyte and dendritic cell (DC) antigen presentation. Both chronic alcohol consumption and chronic HCV infection are independently associated with activation of inflammatory pathways that mediate hepatocellular injury. Thus, we hypothesize that alcohol, HCV interacts to activate non-specific proinflammatory cascades in chronic HCV infection, and this process may contribute to
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progression of liver damage. Based on our preliminary results, we propose that the pattern recognition receptor, toll-like receptor 2 (TLR2), mediates cellular activation by HCV core and NS3 proteins. We further postulate that alcohol may increase inflammatory cell activation by interacting with TLR2-mediated pathways. Our preliminary results show that myeloid DC (dendritic cells), the most potent antigen presenting cell type, have reduced T-cell activation capacity in patients with chronic HCV infection and this can be further decreased by alcohol treatment of DCs. Thus, we propose that alcohol contributes to the persistence of chronic infection in HCV by inhibiting functional maturation of dendritic cells, thereby decreasing antigen-specific T cell activation and viral recognition. The Specific Aims of this proposal are: 1. To investigate interactions between HCV- and alcohol-induced inflammatory pathways at the protein and mRNA levels and on activation of the nuclear regulatory kB/Rel pathway in normal monocytes and in patients with chronic HCV infection with and without alcohol use or chronic in vitro alcohol treatment. 2. To investigate the pattern recognition receptor, TLR2, as a putative receptor in cell activation by HCV proteins. This will be accomplished by testing cellular activation by HCV proteins in TLR2transfected CHO and HEK cells and in macrophages of TLR2-deficient mice. The cooperation of TLR2 with other components of the TLR2 receptor complex required for successful transmission of HCV core and NS3 mediated cell activation will be identified by selectively investigating the roles of CD14, TLR 1, and TLR6. 3. To evaluate the interactions between alcohol and HCV proteins on TLR2-mediated cell activation pathways by determining the effects of acute and chronic alcohol treatment on TLR2 expression, gene activation, and TLR2-mediated monocyte activation from normal controls and chronic HCV infected patients. Investigation of downstream elements involved in TLR2-mediated intracellular signaling after stimulation with core and NS3 proteins and their modulation by alcohol will be tested. 4. To delineate the role of TLR2mediated signaling by HCV core and NS3 proteins in the reduced dendritic cell differentiation in HCV infected patients and to evaluate the effect of alcohol on TLR2mediated signals in DC development. Results from these studies should reveal molecular and cellular mechanisms by which alcohol interacts with HCV infection to accelerate disease persistence and progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERLIPIDEMIA: IMPLICATIONS IN LIVER FIBROSIS Principal Investigator & Institution: King, Kara C.; Biology; University of North Carolina Charlotte Office of Research Services Charlotte, Nc 282230001 Timing: Fiscal Year 2002; Project Start 01-FEB-2002 Summary: (provided by applicant): Hyperlipidemia is characterized by elevated levels of cholesterol and triglycerides and is increasingly prevalent as humans age. Hyperlipidemia has been strongly correlated with heart disease, but its role in other diseases has not been extensively studied. Recent data from our laboratory shows that liver damage develops with age in the hyperlipidemic environment of transgenic mice that overexpress the human apolipoprotein (apo) C-I gene. ApoC-I mice have hyperlipidemia due to impaired lipoprotein clearance, and chronically elevated lipoprotein levels have been associated with the onset of damage to the arterial walls in heart disease. The onset of liver damage seen in our mouse model may be initiated by this condition as well. It is hypothesized that impaired lipoprotein clearance caused by persistent hyperlipidemia leads to oxidative modification of the lipoproteins by reactive oxygen species (ROS). Oxidatively modified lipoproteins may initiate damage to the liver that gets progressively worse with age. It is also hypothesized that caloric
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restriction of hyperlipidemic mice will be effective in reducing lipid levels. This reduction will result in a substantial decrease in both the oxidative modification of lipoprotems and subsequent liver damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDUCTS
IDENTIFICATION
OF
SITES
OF
MDA-ACETALALDEHYDE
Principal Investigator & Institution: Kearley, Mark L.; Associate Professor and Chair; Chemistry; Sonoma State University 1801 E Cotati Ave Rohnert Park, Ca 94928 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): A common result of prolonged alcohol consumption is liver damage. There is a considerable body of evidence that implicates the first metabolite of ethanol oxidation, acetaldehyde (AA), and malondialdehyde (MDA), a byproduct of lipid peroxidation, as the precursors to hepatotoxicity. When proteins are incubated with MDA and AA, hybrid protein adducts, designated as MAA adducts, are generated. To date we have determined the structures of two MAA adducts. One adduct is the fluorescent 1,4-dihydopyridine 3,5-dicarboxaldehyde, formed by a Hantzsch reaction. The other is the nonfluorescent 2-formyl-3-alkylamino-butanal, which results from a Mannich reaction. Both adducts can form on a protein via the t-amino group of lysine or the N-terminus whereas the Mannich adduct can also form on a histidine residue. The research proposed here will focus on identifying the specific sites of MAA modifications on proteins. First, each adduct will be synthesized on model peptides and their mass spectra studied to determine the characteristic fragmentation patterns of each adduct. Next we will MAA-modify human alpha-calcitonin gene-related peptide, a 37 residue peptide that has 2 lysines and 1 histidine, and use mass spectrometry to identify the sites of MAA adduct formation. Finally, the proteins ribonuclease A (RNase A) and soybean trypsin inhibitor (STI) will be used in similar experiments. Both proteins have been extensively studied and their structures are well characterized. In addition, each protein has only 10 lysine residues and thus, mass spectrometry should be able to determine the sites of adduct formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE RESPONSES AND ACHOHOLIC LIVER DISEASE Principal Investigator & Institution: Jerrells, Thomas R.; Professor; Pathology and Microbiology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 07-AUG-2003 Summary: (Adapted from the Investigator's Abstract) Alcoholic liver disease (ALD) is a serious consequence of alcohol abuse and results in a great deal of morbidity and mortality in the United States. The mechanisms that lead to ALD are poorly understood, and it is not known what factors are involved in the susceptibility for the development of ALD. The prevailing opinion is that some factor initiates an inflammatory response in the liver that is uncontrolled and ultimately results in the characteristic fibrosis associated with this process. Data from this laboratory have shown that a condition that resembles the sequence of events in ALD can be initiated in ethanol (ETOH)-fed C57Bl/6 mice after activation of T-lymphocytes by specific antigen or concanavalin A. These activation stimuli induce steatosis and hepatitis only in ETOH-fed mice, which ultimately result in liver damage evidenced by elevated serum levels of ALT and AST. These data support our suggestion that at least one factor involved in initiation and development of ALD is a specific immune response in the liver. To test this hypothesis
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we propose to use these murine models of ALD and a model of viral hepatitis to define the mechanisms responsible for this immune - mediated liver damage. It is our specific hypothesis that initiation of the inflammatory process is the result of specific T cellmediated killing, either through direct cellular cytotoxicity or through the production of cytotoxic cytokines of the infected hepatocyte. Further, we hypothesize that corticosteroid production associated with ETOH consumption has a twofold effect in this system. First, the immune response is suppressed by corticosteroids to inhibit the ability to control the replication of the infectious agents, results in more inflammation. Second, corticosteroids sensitizes hepatocytes to enhance destruction of these cells by either direct T-cell-mediated lysis or lysis mediated by inflammatory cytokines such as tumor necrosis factor. The proposed research will also define the specific cells that initiate or mediate liver damage as well as the role of the inflammatory response and inflammatory cytokines in these models of experimental ALD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE RESPONSES TO ACETALDEHYDE ADDUCTS Principal Investigator & Institution: Klassen, Lynell W.; Stokes-Shachleford Professor and Vice-Ch; Internal Medicine; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-DEC-2003 Summary: Alcoholic liver disease remains a major worldwide health problem. This project will continue studies designed to investigate the hypothesis that metabolically derived aldehydes complex with liver cell proteins forming stable aldehyde adducts that may act as antigens to induce immune responses and play a role in alcohol related liver damage. Recent studies have shown that acetaldehyde and the lipid peroxidationderived aldehyde, malondialdehyde, can react together with proteins in a synergistic manner to form distinct hybrid adducts which have been designated as MAA adducts. MAA adducts have been found in the livers of ethanol-fed rats and are immunogenic with the production of highly specific antibodies in the absence of adjuvants. Additionally, dependent upon the immunizing protein modified, the antibodies can be either to MAA or to the unmodified protein. Experimental models have demonstrated that antibodies to both self and non-self proteins can be generated following adduct modification. Therefore, it is suggested that proteins are modified with MAA as a result of chronic ethanol consumption and thereby induce an unique immune response to the MAA-epitope, as well as to nonmodified epitopes on soluble carrier proteins. The ability of MAA-modified soluble proteins to induce immune responses is dependent on the unique features of antigen processing and presentation, and mechanisms of B- and Tcell immunoregulation. The mechanisms of MAA-induced protein immune responses will be addressed by the following specific aims: 1) Characterize the ability of soluble MAA-adducted non- self (HEL, OVA) and self (MSA) proteins to induce antibody responses in the absence of adjuvant to the MAA epitopes or to unmodified carrier protein epitopes; 2) Determine the T cell proliferative responses to MAA adducted nonself and self soluble proteins following immunization in the absence of adjuvants; 3) Determine the cell types that are involved in the uptake, processing, and presentation of MAA-adducted non-self and self proteins 4) Using an in vitro model of Class I antigen presentation, assess the ability of MAA adducted proteins to induce cytotoxic T cell responses to non-self and self-antigens 5) Identify self liver proteins modified with MAA; Determine the effects of chronic ethanol consumption on each of these processes. Using the assays defined above, assess the in vivo role of MAA in initiating these responses in the presence and absence of chronic ethanol consumption. Overall, these
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Liver Damage
studies will begin to develop the mechanisms by which MAA-modified proteins in the presence or absence of alcohol may induce antibody and T cell responses in the absence of adjuvants. Additionally, they should develop the techniques necessary to assess how endogenous MAA-proteins influence the immune system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIPID ALDEHYDES AND ETHANOL INDUCED LIVER DAMAGE Principal Investigator & Institution: Petersen, Dennis R.; Professor and Vice Chairman; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUN-1993; Project End 31-MAR-2006 Summary: (Adopted from the Applicant's Abstract): The long-range goal of this project is to establish the mechanistic role(s) of aldehydic products of lipid peroxidation (4hydroxynonenal [4-HNE] and malondialdehyde [MDA] in alcoholic liver disease (ALD). It is becoming more apparent that these chemically reactive aldehydes have the potential to interfere with a spectrum of cellular functions ranging from enzyme inhibition to initiation of gene expression. It is our hypothesis that when produced in excess as a result of alcohol-induced oxidative stress, 4-HNE and MDA interact with hepatocellular proteins resulting in altered protein function, impaired protein degradation and the dysfunctional expression of genes involved in various fibrotic processes. This hypothesis will be evaluated it three specific aims using liver tissue and cells obtained from rats and mice administered alcohol by intragastric infusion. In Specific Aim 1, we will continue our characterization of hepatic aldehyde-adducted proteins isolated from rats treated chronically with alcohol. For these studies, the proteins will be immunoisolated, and subjected to matrix assisted laser desorption ionization-time of flight (MALDI-TOF) analysis for amino acid sequence analysis and identification of specific adducted amino acid residues. Experiments proposed in Specific Aim 2 will investigate the potential of 4-HNE and MDA to diminish the transactivation of NFKB complex in hepatic stellate cells, resulting in down-regulation of IL-6 expression. The specific mechanistic events in NF-KB signaling pathway will be evaluated in isolated hepatocytes and stellate cells, including phosphorylation and proteolysis of 1KB proteins, phosphorylation of p65 and PKAc. We will also examine the role of IL-6 in ALD using transgenic IL-6 knockout mice. In Specific Aim 3 we will evaluate how the interactions of 4-HNE and MDA with proteins and the multicatalytic proteinase/proteosome (MCP) alters protein degradation. These experiments will also employ immunoprecipitation/immunoblotting procedures as well as MALDI-TOF analysis to investigate degradation of adducted model proteins using in vitro systems and to identify the molecular targets of adduction involved in impaired hepatic protein degradation by the MCP. These studies will greatly enhance our understanding of the mechanistic role(s) of 4-HNE and MDA in alcohol-induced liver damage. Identification of susceptible cellular targets and specific mechanisms could provide information leading to the development of effective therapeutic interventions for altering specific events involved in ALD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF ACTIVATION OF THE JNK PATHWAY BY BILE ACIDS Principal Investigator & Institution: Gupta, Seema; Microbiology and Immunology; Virginia Commonwealth University Richmond, Va 232980568
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Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): The studies in this proposal address the specific role that signaling pathways play in regulation of bile acid biosynthetic enzymes, specifically the enzyme cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the neutral pathway of bile acid biosynthesis. Recent findings from our laboratory provide strong evidence that activation of the c-Jun N-terminal Kinase (JNK) pathway by bile acids plays a pivotal role in regulation of CYP7A1 in primary rat hepatocytes. However, the molecular events by which bile acids activate this pathway have not yet been fully elucidated, but may have important implications in the pathogenesis of hypercholesterolemia and cholestatic liver diseases. It is proposed that interplay of ceramide and FAS within outer membrane lipid rafts is capable of regulating CYP7A1 through JNK activation. The objectives of this application are to (1) determine the mechanism(s) of activation of the JNK pathway by bile acids by defining the role of the FAS receptor in the activation of JNK in primary hepatocytes, (2) investigate the involvement of sphingomyelinases and ceramide in activation of the FAS receptor by bile acids, (3) determine whether the mechanism(s) of in vitro regulation of CYP7A1 by bile acids also apply in vivo, using FAS and acidic sphingomyelinase knock-out mice. An integrative approach combining kinase assays, ceramide measurements, fluorescence imaging, serum lipid analysis, and other molecular biology techniques will be applied to the proposed studies. Studies will be performed at Virginia Commonwealth University's-Medical College of Virginia Campus. The Department of Microbiology and Immunology and the Liver Centre at VCU are fully committed to support this research endeavor and to further develop the candidate's research career by providing the protected time, resources, and continuing research educational opportunities. This will enable the candidate to achieve her long term career goals of forming a fundamental understanding of bile acid-mediated signaling to serve as a basis for the development of effective therapies to reduce serum cholesterol levels and limit cholestasis-associated liver damage, and to develop an independent and successful research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF ENDOTHELIAL CELL DEATH IN ISCHEMIC LIVER Principal Investigator & Institution: Clavien, Pierre A.; Professor; University of Zurich 71 Ramistrasse Zurich, Timing: Fiscal Year 2002; Project Start 15-JUL-1999; Project End 30-APR-2004 Summary: Ischemic liver injury is a major clinical problem in shock, liver surgery and transplantation. Our initial results allow us to implicate apoptosis of sinusoidal endothelial cells (SEC) - an active process of cell suicide - as a central feature of reperfusion injury in rat models of hepatic ischemia. We have also discovered that calpains, a family of intracytoplasmic calcium dependent cysteine proteases, are activated during periods of ischemia and reperfusion (I/Rp) and in part mediate SEC apoptosis. We HYPOTHESIZE that ischemia sensitizes SEC to the effects of proapoptotic mediators released at the time of reperfusion, resulting in the apoptosis of SEC, even when the direct ischemic damage is reversible. The overall objective of this project is therefore to elucidate in vivo mechanisms of SEC apoptosis in rodent models of hepatic I/Rp, and design protective strategies to improve viability of the ischemic liver. The first objective is to characterize the temporal dynamics of SEC apoptosis in hepatic injury by monitoring characteristic microscopic, histomorphologic and biochemical markers of apoptotic cell death at successive time points during I/Rp.
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Liver Damage
Second, we will determine the cellular mechanisms of calpain- mediated SEC apoptosis by identifying tissue localization of calpain activity and the relationship between calpain activation and other possible calpain related cellular effectors of apoptosis (caspase and ceramide) in a hepatic I/Rp whole-organ model. Third, we will design protective strategies by inhibiting mediators of SEC apoptosis or by manipulations designed to favor anti-apoptotic activities. We have shown that calpain inhibition is effective in protecting SEC in normothermic I/Rp. Unfortunately, calpain inhibitors are not as effective in cold I/Rp injury, relevant for transplantation, and are not water soluble reagents, limiting their clinical applicability. Because many interacting pathways lead to apoptosis, we anticipate that interventions at multiple levels will be necessary. In addition to using new water soluble calpain inhibitors, we will block FAS and TNFalpha, well characterized extracellular pro-apoptotic mediators that may be active in the I/Rp-injured liver. A potential regulatory role for the Bcl-2 gene, whose product is inhibitory at various levels of the apoptotic process, will be investigated using transgenic mice overexpressing Bcl-2. Our whole-organ model is uniquely suited to these studies, since - if known precedents hold - signaling for apoptosis most likely involves complex interactions among several cell types. Identification of mechanisms of SEC death in hepatic I/Rp injury and the ability to protect these cells may have significant clinical impact by allowing longer and safer preservation prior to transplantation and by lessening ischemic liver damage during non- transplant surgery and shock. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF ISCHEMIA REPERFUSION INJURY IN THE LIVER Principal Investigator & Institution: Engelhardt, John F.; Associate Professor; Anatomy and Cell Biology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-AUG-2005 Summary: Orthotopic liver transplantation is a common therapy for many acquired and inherited disorders. Liver damage caused by ischemia and reoxygenation (termed ischemia/reperfusion or I/R) has been proposed to substantially contribute to the initial poor function (IPF) of transplanted livers, acute rejection, and graft failure. Central mediators of I/R injury in the liver are reactive oxygen species (ROS) generated during reperfusion with oxygenated blood. Of the multiple forms of ROS potentially generated during reperfusion, O2-, H2O2, and OH will be addressed in the proposed studies. These ROS can cause direct damage to cellular proteins, lipids, and DNA, or they can act as intracellular second messengers to activate and/or inhibit signal transduction pathways that determine cell fates by altering the expression patterns of stress response genes. Central to the goals of this grant are to determine: 1) Which ROS are pathophysiologically important in I/R damage, 2) How do ROS lead to activation of AP1 and NFkB signal transduction pathways following liver I/R, 3) In which subcellular compartments (i.e., nucleus, mitochondria, endoplasmic reticulum, or cytoplasm) do these ROS act to alter the activity of AP-1 and NFkB signal transduction pathways, and 4) Is activation of AP-1 and NFkB beneficial or detrimental to the liver following I/R injury. Several model systems will be used to address these questions including: 1) Recombinant adenoviral vectors to modulate the cellular redox state and inhibit/activate specific signal transduction pathways, 2) transgenic knockout mice deficient in certain signal transduction components, 3) partial lobar, liver I/R mouse model, and 4) a syngeneic rat liver transplant model. Preliminary data has demonstrated that ectopic expression of MnSOD using reombinant adenovirus protects the liver from
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warm I/R injury and concordantly reduces AP-1 and NFkB activation. The mechanisms of NFkB activation appear to involve redox mediated tyrosine phosphorylation of 1kBalpha. The hypothesis that subcellular compartmentalized ROS are important in mechanisms of liver I/;R injury is supported by the fact that ectopic expression of Cu/ZnSOD does not protect the liver from I/R damage. Based on our findings that OH radicals and AP-1 activation are increased in Cu/ZnSOD but not MnSOD or LacZ expression livers, and inhibition of Rac1 pathways by expression of the dominant inhibitor N17Rac1 also activates AP-1, one novel focus of our mechanistic studies on AP-1 activating following I/R injury will involve Rac1/PI3-kinase /PKK/GSK modulation of c-Jun phosphorylation. Recombinant adenoviral mutants for the proteins in this signal transduction pathway will be used to dissect its importance. Using recombinant expressing dominant inhibitors and transgenic knockout mice to block either AP-1 and NFkB activation, we will attempt to determine the importance of each of these pathways in mediating both acute hepatic toxicity and subacute inflammatory responses following I/R injury. In the last phase of this proposal, studies will be aimed at determining the relevance of findings in our mouse partial lobar warm I/R model to the rat liver transplant model of cold ischemia. In summary, this proposal will provide experimental and mechanistic paradigms for linking ROS formation in the liver following I/R injury to both acute damage and subsequent inflammation. Moreover, these studies may provide clinically relevant gene therapy approaches for minimizing organ damage following transplantation, which may ultimately increase the graft survival in orthotopic liver transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MITOCHONDRIAL GSH /SAM IN ALCOHOL INDUCED LIVER DAMAGE Principal Investigator & Institution: Fernandez-Checa, Jose C.; Fundacio Clinic C/Villarroel 170 Barcelona, Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Since we first discovered in 1987 the depletion of mitochondrial GSH (mGSH) status by chronic ethanol intake, considerable progress has been made regarding the molecular mechanism(s) of the defect and its functional impact in alcohol-induced liver damage (ALD). In addition to the altered regulation of mGSH by alcohol, S-adenosyl-L-methionine (SAM) depletion has been also reported and is thought to contribute to the progression of the disease. GSH and SAM may exhibit parallel features as both are found in mitochondria due to specific transport mechanisms. Thus, the present proposal will look at the specific regulation of mitochondrial SAM (mSAM) pool by alcohol and the temporal and functional relationship between mGSH and mSAM by alcohol. 1. - SAM levels and transport in rat liver mitochondria from alcohol-fed rats. Most studies have reported the status of total SAM levels in hepatocellular extracts in patients and experimental models of ALD. We wilt examine the status of mSAM levels and its mitoehondrial transport in chronic alcohol-fed rats. 2. Temporal and functional relationship between mitochondrial GSH and SAM depletion by alcohol: Role of Kupffer cells and liver steatosis. We will examine if mGSH depletion by alcohol precedes or follows that of SAM (total and mSAM) in mitochondria from alcohol fed rats and its relationship with pathology. The role of Kupffer cell activation and liver steatosis on alcohol-mediated mGSH and total SAM (cytosol and mSAM) depletion will be evaluated in alcohol-fed rats and in a model of non-alcohol: hepatic steatosis. 3. Mechanism whereby SAM feeding normalizes the alcohol-altered mitoehondrial membrane fluidity and mGSH transport. Increasing
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Liver Damage
evidence indicate a critical role of cholesterol/phospholipid molar ratio in the regulation of mitochondrial membrane mieroviseosity and mGSH transport, in addition to these changes, we wilt examine the regulation and trafficking of cholesterol into mitoehondria, as well as the fatty acid composition of individual lipids of mitochondrial lipid classes from chronic alcohol-fed rats with or without SAM supplementation. 4. Regulation of MAT1A by glycosphingolipids and sphingomyelinases. TNF and shortchain ceramide have been reported to downregulate the expression of MAT1A. Since sphingomyelinases (SMases) are known to mediate some of the effects of TNF, we will examine the role of individual neutral or acidic SMase, in the regulation of MATIA in primary cultured rat hepatocytes and HepG2 cells exposed to exogenous neutral (NSMase) or acid (ASMase) SMases. In addition, we will assess the role of TNF on MATIA expression in ASMase knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NONALCOHOLIC FATTY LIVER DISEASE IN HISPANIC OBESE YOUTH Principal Investigator & Institution: Butte, Nancy F.; Associate Professor of Pediatrics; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Childhood obesity and type II diabetes are reaching epidemic proportions in the U.S. particularly among Hispanic and African-American children, and the consequences of this epidemic in terms of nonalcoholic fatty liver disease (NAFLD) are understudied and under appreciated. Hispanic and AfricanAmerican children are at greater risk for the development of obesity and type II diabetes which are major risk factors for NAFLD. The full impact of this metabolic syndrome will not be realized until these children become adults and develop the long-term consequences of obesity, diabetes and liver disease. The primary objective of this grant is to characterize children at risk for NAFLD and explore possible mechanisms underlying the development of NAFLD in 1000 Hispanic children enrolled in an ongoing NIH genome-wide linkage study designed to identify genes that influence the expression of childhood obesity. The long-term objective is to develop an clinical intervention trial to treat the adverse effects of NAFLD in obese children. Hypothesis: Oxidative stress, endotoxemia and systemic inflammation superimposed on hepatic fat accumulation may lead to liver damage in obese children. Specific Aims: 1. To characterize Hispanic children at high risk of developing NAFLD in terms of age, gender, body composition, diet, physical activity, and severity and duration of obesity. 2. To determine the relationships between fasting hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperleptinemia, and elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). 3. To obtain evidence that oxidative stress, endotoxemia and measures of systemic inflammation are associated with elevations in serum ALT and AST. Design: Obese Hispanic children and their nonobese siblings will be screened for NAFLD using serum liver function tests; total sample size will be 1000. We will characterize children at risk for NAFLD and explore possible mechanisms of oxidative stress, endotoxemia and systemic inflammation underlying NAFLD. Methods: Liver function tests, ALT and AST will be analyzed in relation to in-depth phenotyping and genetic linkage analysis performed under the on-going NIH study. Newly proposed tests include chromogenic assays to measure lipid peroxidation end products and endotoxins, and ELISA and RIA to measure cytokine and markers of systemic inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL APPLICATION
ALT
ISOENZYMES
AND
THEIR
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DIAGNOSITC
Principal Investigator & Institution: Gong, Da-Wei; Assistant Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): For nearly fifty years, alanine transaminase (ALT) has been a widely used clinical diagnostic marker of acute and chronic hepatic injury. Although elevated serum ALT is a common feature of liver damage, it is also observed in other diseases such as obesity, muscle disease, and in apparently healthy people. The cellular mechanisms leading to ALT changes in the above situations are poorly understood, which often renders the interpretation of ALT data problematic. The work proposed in this application is based upon our recent discovery of a novel homologue of human ALT, which we have designated ALT2. ALT2 has significant homology to ALT1 (the only previously known ALT) with 69% identity and 78% similarity at the peptide level. Importantly, the two isoenzymes are encoded by distinct genes and differ significantly in tissue distribution; ALT2 is highly expressed in muscle, kidney and adipose tissue, whereas ALT1 is mainly expressed in liver, kidney and heart. Since current assays to measure serum ALT levels are enzymatic, they do not differentiate between ALT1 and ALT2. Measurement of an isoenzyme in serum may have more diagnostic value than total enzyme activity, as exemplified by creatine kinase-MB for cardiac infarction and bone-specific alkaline phosphatase for bone disease. We hypothesize that ALT2 circulates in serum and contributes variably (depending on disease etiology) to total ALT activity measured in currently available clinical assays. Furthermore, we hypothesize that ALT2 will be particularly elevated in patients with fatty liver and/or obesity, since ALT2, but not ALT1, is abundantly expressed in adipose tissue. To examine these hypotheses, we propose to develop an ALT isoenzyme-specific immunoassay. This assay will be used to measure serum levels of ALT isoenzymes in a host of disease states including liver disease and obesity (stable and during weight loss). We predict that serum ALT2 will be higher in patients with fatty liver or obesity and may be a clinically useful marker for this and other disease states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUTRITION INTERVENTION: METABOLIC COMPLICATIONS OF HIV+ Principal Investigator & Institution: Woods, Margo N.; Associate Professor; Family Medicine & Cmty Health; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): As the HIV population survives and ages, a new syndrome is being observed that appears to be affected by PI medications but is also seen independent of PI use. This syndrome is characterized by hyperlipidemia, lipodystrophy and insulin resistance. Elevated triglycerides are a common observation with or without hypercholesterolemia. Since statin do not reduce serum triglycerides and may be counter-indicated to lower serum cholesterol because of potential liver damage in the HIV+ population that are on PI, dietary interventions have been getting more attention. Literature suggests that a diet lower in fat with reduced levels of saturated fat relative to polyunsaturated fat, increased omega 3-fatty acids intake, high fiber, and use of carbohydrates lower in glycemic index may be beneficial when they were studied individually. We propose to use a nutrition intervention in a HIV+ population that has elevated triglycerides (>220 mg/dl) to test whether a diet that
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combines all of these factors can have a significant effect on reducing serum triglycerides. The nutrition intervention will be a low fat diet (25% of calories from fat) with a 1:1:1 ratio of Saturated:Monounsat: Polyunsaturated fat, high in fiber (40 g/day) with carbohydrates of lower glycemic index (< 70 whenever possible). This diet will contain 3 g/day of omega 3-fatty acids which will be supplemented with 3.0 g of omega 3-fatty acids from capsules to give a total of 6 g/day of omega 3-fatty acids and a ratio of n-6/n-3 of 4:1. In addition to measuring triglycerides, serum cholesterol and its subfractions will be determined as well as insulin area under the curve (AUC) and body composition using CT scan. HIV+ participants eligible for the study (N=100) would be randomized into a control or nutrition intervention group and be tested for changes after 3 weeks, 13 weeks and 6 months of intervention. During the first 3 weeks the intervention group will be given all their meals at the hospital General Clinical Research Center, followed by an additional 10 weeks in which some food products are supplied to them along with the continued use of omega 3-fatty acids supplements at 3 gms/day (in 10 capsules). After 13 weeks the participants will be asked to continue to take the omega 3-fatty acid capsules but food products high in n-3 fatty acids will not be supplied. A 6-month follow-up will then remeasure all the study parameters to determine if the nutrition intervention group had experienced an improvement of the listed risk factors compared to the control group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC TRIALS IN NON-ALCOHOLIC STEATOHEPATITIS (NASH) Principal Investigator & Institution: Lavine, Joel E.; Professor and Vice Chair; Pediatrics; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-APR-2007 Summary: (provided by the applicant) Pediatric hepatologists in the Joint Program in Pediatric Gastroenterology, Hepatology and Nutrition at the University of California, San Diego propose their inclusion as a Clinical Center in the "Clinical Research Network in Non-Alcoholic Steatohepatitis". Although NASH generally is regarded as a common condition in adults, recent research reveals that NASH is one of the most common causes of liver disease in 10-18 year olds. This application proposes UCSD participation as a center on the basis of past experience of the Principal Investigator with pediatric NASH, the number of children available to our center for studies, and the ethnic diversity of our population based on our unique geographic location. Cooperation of UCSD adult hepatologists and Scripps Clinic hepatologists for referral of adult patients with NASH will allow participation in proposals initiated by other centers in the clinical research network which focus on adults. Our NIH-funded General Clinical Research Center will facilitate all facets of proposed studies. Our application provides a template for preparation of a multicenter database and tissue/serum bank to study pediatric NASH, based on knowledge and experience of the presentation and proposed pathophysiology of the condition. Two proposals are detailed in this application. The first is a prospective, multi-center, epidemiologic analysis of factors associated with the development of NASH in obese children, evaluating the role of age, race and gender. Potential factors involved in pathogenesis will be assessed with respect to pubertal development, insulin resistance, increased exposure to mediators of inflammation, and increased indicators of oxidative stress. The second study is a prospective, multi-center, randomized, double-blind trial evaluating treatment of childhood NASH with Vitamin E versus placebo. Children randomized to placebo will serve as a long-term cohort to understand the natural history of this untreated condition with early onset. The treated
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children, who in previous open-label pilot studies have been shown to normalize serum markers of liver damage, will be rigorously studied to determine if antioxidant therapy improves outcome as assessed by changes in liver histology and markers found associated with NASH pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEROXYNITRITE HEPATOTOXICITY
IN
ACETAMINOPHEN
INDUCED
Principal Investigator & Institution: Hinson, Jack A.; Professor and Director; Pharmacology and Toxicology; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: Although safe at therapeutic doses, overdoses of acetaminophen produce a centrilobular hepatic necrosis that can be fatal. Each year, more than 9,000 individuals in the US sustain liver damage due to acetaminophen, with 53 deaths reported in 1996. The rationale for this proposal is based on key findings from our preliminary work that challenge the currently accepted paradigm of toxicity. It is generally accepted that acetaminophen is metabolized by CYP-450 to the reactive metabolite, N-acetyl-pbenzoquinone imine (NAPQI), which reacts with GSH, leading to its depletion (and thus decreased peroxide detoxification), and subsequently forming acetaminophen-protein adducts. Our findings indicate that metabolism of acetaminophen to NAPQI may not be the sole determinant of cell lysis and death. We find that the metabolic stress activates resident cells, leading to increase synthesis of nitric oxide (NO) and superoxide, which combine to form peroxynitrite. This entity reacts to form nitrotyrosine-protein adducts and has hydroxyl radical like activity. We detect nitrotyrosine-protein adducts in the hepatic centrilobular cells of acetaminophen-treated mice, the site of the toxicity. Thus, based on this and other preliminary data, we propose a paradigm of acetaminophen hepatotoxicity whereby peroxynitrite generation, coupled with acetaminophen-protein adduct formation, act synergistically to cause cell lysis and death. We hypothesize that peroxynitrite generated during or as a result of acetaminophen metabolic activation is a major determinant of acetaminophen hepatotoxicity. To test this hypothesis, we plan to SA1) Determine the time and dose relationships between acetaminophen metabolism, NO formation, and development of toxicity; SA2) Investigate the roles of NO, superoxide, and peroxynitrite generation in acetaminophen hepatotoxicity by inhibiting NO formation and by using NO, superoxide, and peroxynitrite scavengers; and SA3) Identify the liver cells responsible for NO and superoxide generation during acetaminophen hepatotoxicity. By understanding the role of peroxynitrite in acetaminophen hepatotoxicity, new treatment paradigms may be developed for hepatotoxicity, and this mechanism may be important with other toxins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POST-ISCHEMIC LIVER INJURY BY REACTIVE METABOLITES OF OXYGEN AND NITROGEN Principal Investigator & Institution: Grisham, Matthew B.; Professor; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Hepatic ischemia and reperfusion (I/R) injury is a complication of liver transplantation and resectional surgery, hemorrhagic and endotoxin shock and thermal injury. A growing body of experimental data suggests that
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I/R-induced liver damage occurs in a biphasic manner involving an early reactive oxygen specie (ROS)-dependent and a late, PMN-dependent phase. Recent evidence suggest that ROS and NO as well as certain pro-inflammatory cytokines (e.g. TNFalpha, IL-1alpha, IL-12) play important roles in modulating post-ischemic liver injury. However, neither the specific cell types nor the sources for ROS and NO production nor their relationship to cytokine expression and hepatocellular injury have been explored. The overall objective of this proposal is to better understand the mechanisms by which ROS and NO-derived metabolites modulate tissue injury in a murine model of liver I/R injury in vivo. Hypothesis: We propose that the oxidative redox imbalance created by the overproduction of ROS and/or by the decreased bioavailability of NO in the postischemic liver activates nuclear transcription factor kB (NF-kB) thereby promoting the expression of both injurious proinflammatory cytokines (e.g. TNF-alpha, IL-1alpha, IL12) as well as protective proteins (e.g. MnSOD, A20, B-c12, c-IAPs). We propose that it is an early imbalance between the expression of these NF-kB-dependent cytokines and protective proteins in favor of the former that initiates I/R-induced liver injury. We suggest that post-ischemic liver injury is limited by the upregulation of the NF-kBdependent protective genes. In order to test this hypothesis, we intend to: a) Characterize the temporal relationship among reactive oxygen species production, NFkB-dependent expression of injurious cytokines and protective proteins and cell injury using Kupffer cells, sinusoidal endothelial cells and hepatocytes isolated from control and post-ischemic livers, b) Determine the role of NF-kB in modulating I/R-induced liver injury, c) Investigate the role that reactive oxygen species play in regulating postischemic liver injury and d) Define the role that NO plays in modulating the ROSdependent activation of NF-kB and subsequent expression of injurious and protective mediators in the post-ischemic liver. Understanding the mechanisms by which these pro-inflammatory cytokines are regulated in vivo may provide new insight into the pathogenesis of liver I/R injury and may lead to more rational approaches to the design of new drug therapies for the treatment of post-ischemic liver damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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
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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 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: RECEPTOR GUANYLYL CYCLASES IN REGENERATING LIVER Principal Investigator & Institution: Russell, William E.; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Our long-term goal is to understand the mechanisms that control the growth, differentiation, and regeneration of the liver. This study focuses on the mechanisms by which liver growth and function is regulated by receptor guanylyl cyclases, molecules that link extracellular signals to the generation of cyclic GMP (cGMP), a critical intracellular signaling molecule. Among other known actions, cGMP is strongly linked to mechanisms regulating programmed cell death, or apoptosis. Within hours of liver damage or cellular loss, there is a dramatic upregulation of guanylyl cyclase C, a cGMP-forming receptor guanylyl cyclase. GC-C is activated by the proteins guanylin and uroguanylin. During regeneration, the liver is exposed to a number of hormones and growth factors, most notably TNF-alpha, which are known inducers of apoptosis. The central hypothesis of this proposal is that ligandmediated activation of the receptor guanylyl cyclases protects regenerating hepatocytes and non-parenchymal cells from the lethal actions of the various cytokines involved in the regenerative response. The guanylyl cyclases may also be critical to restraining hepatocyte proliferation to achieve normal liver mass and to prevent neoplasia. We aim to determine: 1) how liver regeneration in response to three different stimuli is altered in GC-A or GC-C gene-targeted mice; 2) the consequences of particulate guanylyl cyclase activation on apoptosis and cell proliferation; and 3) how membrane guanylyl cyclases alter apoptotic signaling mechanisms in cultured hepatocytes and in regenerating liver. Progress toward these aims will improve our understanding of how the liver inhibits programmed cell death during the dramatic restoration of liver growth of regeneration. Liver regeneration is a paradigm for other conditions of normal and altered growth regulation, including tissue hypertrophy, wound healing, and cancer. In addition to elucidating mechanisms of growth control in the liver, our studies may ultimately aid in developing methods to reduce liver cell death following viral or toxic injury during transplantation and in the differentiation of precursor cells for transplantation and bioartificial livers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF HBV REPLICATION BY THE IMMUNE SYSTEM Principal Investigator & Institution: Guidotti, Luca G.; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): The hepatitis B virus (HBV) causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma. Over 350 million people worldwide are persistently infected by HBV, representing an enormous reservoir for horizontal and vertical spread of this virus to others. The long term objective of this application is to elucidate the molecular basis for liver disease, viral clearance and viral persistence in the pathogenesis of HBV infection with the ultimate hope that this knowledge will lead to the development of new therapeutic strategies to terminate persistent infection and its attendant costs and complications. Using transgenic mice that replicate HBV at high levels in the liver as recipients of HBV-specific CTLs, we have shown that the antiviral potential of the CTLs is primarily mediated by noricytolytic mechanisms that involve the intrahepatic production of type I inflammatory cytokines by these cells. This occurs after the CTLs specifically recognize viral antigens on the surface of the hepatocyte. Following antigen recognition, the CTLs also trigger the death of a small number of hepatocytes and this process leads to the recruitment of many hostderived lymphomononuclear and polymorphonuclear cells into the liver that contribute to the formation of necroinflaminatory foci histologically identical to classical viral hepatitis in man. The recruited inflammatory cells are likely to be responsible for antigen-nonspecific amplification mechanisms that greatly enhance the liver damage initiated by the CTLs. The recruitment of these cells is probably mediated by secretion of chemokines by either the antigen-activated CTLs or other cellular components of the liver. In support of this, we have performed preliminary experiments showing that a large variety of chemokines are rapidly and strongly induced in the liver of HBV transgenic mice after CTL transfer and their expression is regulated by type 1 inflammatory cytokines. Chemokines are likely to play a role in viral pathogenesis by regulating the trafficking of inflammatory cells to tissue sites of infection and, perhaps, by directly inhibiting viral replication. Whether this is the case during HBV infection is not known. To explore these hypotheses, we will use in vivo (HBV-replicating transgenic mice) and in vitro (HBV-replicating hepatocytes) systems to determine the function of chemokines and chemokine receptors on the recruitment, antiviral and pathogenic effector functions of CTLs and other inflammatory cells. We will also define the role that type 1 inflammatory cytokines may play in these processes. The results of these experiments will provide insight into the basic immunological processes that may determine liver disease, viral clearance and viral persistence in the pathogenesis of HBV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF IL-4 DURING ACUTE SCHISTOSOMIASIS Principal Investigator & Institution: Patton, Elisabeth A.; Comparative Biosciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 21-FEB-2003 Summary: (adapted from applicant's abstract): Schistosoma mansoni is a parasitic helminth of significant public health concern. Clinical disease is due to the granulomatous response to eggs that become trapped in the liver. In most people and all laboratory wild type mice, S. mansoni leads to the development of a strong Th2 response concurrent with the onset of parasite egg production. Although the granuloma
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induced by the Th2 response results in liver damage, it is critical for host protection. This is demonstrated in IL- 4-/- mice during S. mansoni infection. These animals are unable to mount a Th2 response and suffer from debilitating cachexia and enhanced mortality subsequent to the onset of egg production. One of the aims of this proposal is to address the role of inflammatory mediators in the development of severe cachexia and mortality in IL-4-/- mice. During severe disease in schistosome- infected IL-4-/mice, splenocytes produce increased inflammatory mediators including NO and TNFalpha, in vitro. TNF-alpha contributes to severe disease as treatment with anti-TNFalpha antibody prolongs time to death in infected IL-4-/- mice. One hypothesis is that egg excretion results in increased endotoxin translocation across the gut wall and in mice lacking the ability to mount a Th2 response, severe inflammation ensues. This hypothesis will be tested by generating an IL-4-/- mouse strain that is hypo-responsive to LPS, the IL-4/TNF-receptor-1 double knockout strain and by generating an IL-4-/strain that lacks exposure to LPS, a gnotobiotic IL-4-/- strain. The course of disease and in vitro responses will be followed in these strains; it is anticipated that if endotoxin induces the severe disease in infected IL-4-/- mice, cachexia and mortality will be minimized in theses strains. The second aim of this proposal focuses on determining the importance and cause of a defect in splenocyte proliferation that has been observed in infected IL-4-/- mice. Mediators such as TGF-beta and NO are elevated in IL-4-/- mice during infection and are improved in infected IL-4-/- animals. The role of TGF-beta in inhibiting the signal transduction cascade which leads to T-cell proliferation will be evaluated. The level at which proliferation is inhibited by both NO and TGF-beta will be determined through analysis of activation of signaling proteins important in proliferative response and the levels of expression of cdks and cdk inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SAME INHIBITS INFLAMMATORY-MEDIATED ENHANCED TOXICITY Principal Investigator & Institution: Maddox, Jane F.; Nat Food Safety & Toxicol Ctr; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Injury to hepatocytes by toxicants such as ethanol and allyl alcohol is a multi-faceted process, leading to cellular dysfunction and cell death via pathways that are not clearly defined. 80me of the mechanisms proposed to contribute include glutathione depletion and subsequent oxidant stress in the cell. In addition, these toxicants alone, or in combination with other agents, may induce the production of endogenous mediators that further damage hepatocytes. S-adenosyI-Lmethionine (SAMe) is a nutritional supplement that appears to have positive effects as a treatment for liver injury caused by hepatotoxicants, though its mechanisms of action are not clearly understood. SAMe is a methyl donor and a precursor for the antioxidant molecule glutathione. The intent of this proposal is to use allyl alcohol as a model for toxicant-induced hepatocyte injury, and determine the role of SAMe in attenuating the cellular damage. In addition, this laboratory has determined that allyl alcohol liver damage is augmented by the endogenous compound 15- deoxy-prostaglandin J2 (15dPGJ2). Allyl alcohol and 15d-PGJ2 are proposed to act in an additive manner to deplete glutathione and inhibit the activation of nuclear factor (NF) kB, leading to decreased production of survival proteins and hepatooyte death. The overall hypothesis to be tested is that SAMe inhibits allyl alcohol toxicity and 15d-PGJ2 augmentation of this toxicity via stabilizing glutathione levels and establishing an oxidant balance in the cell, thus maintaining healthy mitochondda and a normalized NFkB activation status.
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Subcellular localization (cytosol versus mitochondda versus nucleus) of glutathione depletion may be important in determining NFkB activation and cell fate. The following specific aims will be tested: 1) SAMe inhibits glutathione depletion by allyl alcohol and 15d-PGJ2 in hepatocytes, thus decreasing cytotoxicity. 2) SAMe counteracts oxidative stress in hepatocytes due to GSH depletion caused by allyl alcohol and augmented by 15d-PGJ2, thereby maintaining a normalized NFKB activation status and decreasing cytotoxicity. 3) SAMe corrects hepatocyte mitochondrial dysfunction caused by allyl alcohol and 15d-PGJ2. 4) SAMe inhibits allyl alcohol and 15d-PGJ2-induced hepatocyte toxicity, whether cell death occurs via apoptotic or necrotic pathways. These experiments will give insight into the potential interaction of an endogenous product, 15d-PGJ2, in the complex relationship of toxicants, somatic response elements and therapeutic agents in determining liver health and cell survival. Results from these studies will increase our knowledge of the mechanism of action of an alternative medicine already in common use, SAMe, in countering the injurious actions of hepatotoxicants, with allyl alcohol as a model. Moreover, they may provide evidence for development of related therapeutic compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SAME, RXRALPHA-MEDIATED PATHWAYS AND ALD Principal Investigator & Institution: Wan, Yu-Jui Y.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The goal of this project is to study the mechanism underlying nuclear receptor retinoid x receptor et (RXR-alpha)-mediated pathways on regulating S-adenosyl-L-methionine (SAMe) homeostasis. The main hypothesis is that RXR-alpha-mediated pathways either directly or indirectly control SAMe synthesis and alter the levels of glutathione and phosphatidylcholine in the liver, which consequently play a crucial role in the development of alcoholic liver disease (ALD). Most of the retinol and alcohol studies rely on either feeding animals with excess amount of retinoids or introducing animals with retinol deficient diet. Feeding animals with retinoids can be toxic. Retinol deficiency can also cause many unwanted effects. Knockout technology avoids these potential problems. Tissue specific knockout further allows studying the function of the gene in a cell type specific manner without affecting the gene function systemically. We have established an animal model in that the RXRalpha gene is knocked out only in the hepatocyte. RXR-alpha is highly expressed in the liver and is required for almost all the nuclear receptor-mediated pathways. Therefore, hepatocyte RXR-alpha deficient mouse serves as an excellent model for studying retinoid signaling in alcoholic liver disease. When hepatocyte RXR-alpha is deficient, liver retinoic acid is elevated, alcohol elimination rate is increased and alcohol-induced liver damage becomes more severe. In addition, the expression of more than ten genes encoding enzymes involved in the SAMe pathway is altered. Those data indicate that RXR-alpha, SAMe and ALD are intricately interlinked. Two specific aims are proposed to study the direct and indirect effect of RXR-alpha on SAMe homeostasis. First is to examine how RXR-alpha-mediated pathways regulate alcohol metabolism, which may indirectly control SAMe synthesis and affect the development of ALD. Second is to characterize how RXR-alpha-mediated pathways regulate genes encoding enzymes in the SAMe pathway and directly control SAMe homeostasis. RXR-alpha-mediated pathways including PPARcz and 3' and RXR-alpha homodimer and others will be studied. The effect of those nuclear receptor ligands on regulating SAMe synthesis will be analyzed. The proposed study not only allows us to understand how nuclear
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receptors regulate SAMe homeostasis, it also provides an opportunity to identify potential therapeutical targets and treatment agents for ALD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THIAZOLIDINEDIONE-INDUCED HEPATOTOXICITY Principal Investigator & Institution: Harvison, Peter J.; Associate Professor; Pharmaceutical Sciences; University of the Sciences Philadelphia in Philadelphia Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Various agricultural, industrial, and pharmaceutical agents contain 2,4-thiazolidinedione (TZD) rings. For example, a TZD ring is found in the insulin-sensitizing agents, troglitazone, rosiglitazone and pioglitazone, which have been or are used in the treatment of type II diabetes. Although the toxicology of the TZD ring has not been extensively investigated, troglitazone was removed from the market after it was associated with over 70 cases of hepatotoxicity that required transplants or resulted in deaths. There have also been reports of liver injuries in patients taking rosiglitazone and pioglitazone. The mechanism by which these drugs damage the liver is not known, although metabolism in the TZD ring may be a factor. Unfortunately, there are no reliable animal models to investigate this process. Recently, 3-(3,5dichlorophenyl)-2,4- thiazolidinedione (DCPT) was found to reproducibly cause liver damage in rats. Since this compound also contains a TZD ring, it is conceivable the presence of this structural feature may be critical for the production of hepatotoxicity. Therefore, DCPT may be a useful model compound to investigate TZD ring-induced liver damage in a commonly used laboratory animal species. In analogy to the insulinsensitizing agents, it is also conceivable that DCPT must undergo metabolism before liver damage will occur. The current proposal is designed to examine the hypothesis that biotransformation in the TZD ring contributes to the hepatotoxicity of DCPT in rats. This hypothesis will be tested through the following Specific Aims: (1) investigate the effect of structural modification on DCPT-induced liver damage in rats to determine if the TZD ring is essential for liver damage; (2) examine of the effect of metabolic enzyme activity modulation on DCPT-induced hepatotoxicity in rats to establish if metabolism in the TZD ring is required for hepatotoxicity; and (3) investigate the potential formation of reactive intermediates from DCPT in vitro, in an effort to elucidate the nature of any putative toxic metabolites that may be generated via biotransformation. The reproducible liver damage that DCPT causes in an animal model may provide a unique opportunity to investigate the potential participation of the TZD ring in liver damage. Since people are exposed to TZD ring-containing compounds, this work may form the basis for future studies about TZD ring-induced hepatotoxicity in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSGENIC HEPATOPROTECTIVE DR*
PLANT
CELLS
AS
SOURCE
OF
Principal Investigator & Institution: Littleton, John M.; Professor; Naprogenix, Inc. Naprogenix Corporate Offices Lexington, Ky 40509 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2004 Summary: Transgenic plant cells as source of hepatoprotective drugs. Alcoholic liver damage (ALD) is among the ten most common causes of death in the USA. The liver may be uniquely sensitive because it metabolizes ethanol at a high rate. This generates acetaldehyde intracellularly, damaging cell components directly, and/or inducing
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apoptotic cell death. Although some plant natural products are protective it would be of value to discover agents with greater efficacy against ALD. Here, a novel biotechnology, based on selection of mutant plant cells for resistance to alcohol, followed by high throughput pharmacological screening (HTPS) of extracts from surviving cells, is applied to this problem. The mutant population will be generated by activation tagging mutagensis, and extracts from the resulting alcohol-resistant clonal cultures screened for protection of hepatocyte cultures against ethanol-induced damage. However, because plant cells in culture metabolize ethanol to a very limited extent, we propose first to produce transgenic plant lines (N tabacum) over-expressing the activated gene for plant or mammalian ADH. Cell cultures derived from these plants will be evaluated for similarities to mammalian liver cells in metabolism of ethanol to acetaldehyde. Phase 1 is the creation of these ADH-expressing (ADHE) lines. In subsequent phases, hepatoprotective compounds from resitant clonal extracts will be tentatively identified by GC/MS. Regardless of whether novel compounds are discovered, the ADHE plant lines, and the ethanol resistant clonal cultures are patentable and represent a valuable resource for development of alcohol-related medications in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTION Principal Investigator & Institution: Whitfield, John B.; Queensland Institute of Medical Research Herston Brisbane Qld, 4006 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This resubmission is one of a group of Interactive Research Project Grant applications, which have the broad objective of clarifying the role of genes in alcohol dependence and related disorders. Alcohol dependence is a common condition with a substantial genetic component. This application focuses on pre-clinical alcoholic liver disease in a community-based sample and will complement published studies on patients with more advanced disease. The objective is to identify risk factors able to predict which hazardous drinkers are at risk of eventual progression to liver disease. Successful identification of risk factors for alcoholic liver disease may lead to improvements in early identification of people at risk from their drinking, and early intervention to prevent progression to clinical disease. Known risk factors include lifetime quantity of alcohol consumed, and gender (women are more susceptible to alcoholic liver disease than men). The postulated risk factors to be studied are based on a small number of published studies on patients, and on our preliminary work with community samples. They include obesity and related metabolic disorders; iron overload; and allelic variation in a range of candidate genes concerned with alcohol metabolism, inflammatory response within the liver, fatty liver and fibrosis. The specific aims are to test whether the postulated risk factors affect the probability of liver dysfunction in hazardous drinkers, using biochemical liver function tests to detect preclinical liver damage. The enzyme liver function tests are abnormal in a substantial proportion (approximately 30-40%) of hazardous drinkers and offer an opportunity for noninvasive testing in large numbers of subjects. Subjects will be drawn from twins and their families who have participated in previous studies of alcohol use and dependence. They will have met DSM-IV criteria for alcohol dependence and/or have reported hazardous levels of alcohol intake in the previous studies. They will provide information on recent alcohol intake, and blood samples will be taken for biochemical testing and as a source of DNA for genotyping. Data will be analyzed using standard methods for twin studies and tests will be included for the effects of postulated
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phenotypic risk factors, for heritability of liver abnormality conditional on hazardous drinking, and for allelic association at candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VESICLE TRANSPORT REGULATION IN INTOXICATION AND DISEASE Principal Investigator & Institution: Runnegar, Maria T.; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract) Microcystins are Peptide hepatotoxins produced by cyanobacteria present in water bodies including portable water supplies, constituting an environmental public health hazard. Okadaic acid and related compounds are the toxic components causing diarrheic shellfish poisoning through the consumption of contaminated shellfish. The mode of action of okadaic acid and microcystins is the potent, specific inhibition of the ser/thr protein phosphatases 1 and 2A. Even a modest degree of phosphatase inhibition in hepatocytes results in impaired microtubule-dependent transport, membrane trafficking, and receptormediated endocytosis, with increased phosphorylation of several components of the microtubule-based motor protein, cytoplasmic dynein. Our thesis is that in liver, changes in the phosphorylation of the dynein complex cause changes in motor activity. This translates into impaired membrane trafficking, affecting essential cellular/organ functions like endocytosis and transcytosis. The specific aims of this proposal are: 1) How is the phosphorylation of cytoplasmic dynein and associated polypeptides regulated? 2) How do changes in phosphorylation of cytoplasmic dynein and associated proteins contribute to changes in dynein activity ? What is the mechanism for these effects? 3) Do changes in the phosphorylation and activity of the cytoplasmic dynein complex lead to altered endocytic membrane traffic? Completion of these studies will increase our knowledge of basic liver function as well as provide insights into the long term consequences for chronic low dose ingestion of these toxins through the water supply or elsewhere. Disruption of membrane traffic because of motor and/or MT changes, be they genetic or environmental, will cause impaired hepatic function and disease. A better knowledge of the control of the components involved in traffic as proposed in this application will lead to novel therapeutic strategies in the event of toxicological or pathophysiological liver damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, 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.
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and type “liver damage” (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 damage in the PubMed Central database: •
Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement? by Croft AM, Herxheimer A.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101408
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Defective TNF-[alpha] --mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice. by Garcia-Ruiz C, Colell A, Mari M, Morales A, Calvo M, Enrich C, Fernandez-Checa JC.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151862
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Hepatitis C Virus Core Protein Leads to Immune Suppression and Liver Damage in a Transgenic Murine Model. by Soguero C, Joo M, Chianese-Bullock KA, Nguyen DT, Tung K, Hahn YS.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136450
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Liver damage and protective effect of high density lipoprotein cholesterol. by Salonen JT.; 2003 Nov 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=261742
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Liver damage main reason drugs pulled from market. by [No authors listed]; 2001 Jun 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81208
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 damage, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “liver damage” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for liver damage (hyperlinks lead to article summaries): •
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A case of acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg with remission of liver damage after long-term treatment with interferon. Author(s): Muraoka H, Sanefuji T, Keida R, Tsuji R, Abe H, Uchimura Y, Noguchi S, Suzuki H, Sata M, Tanikawa K. Source: Kurume Med J. 1995; 42(4): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8667603
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 case of CREST syndrome with rapidly progressive liver damage. Author(s): Yabe H, Noma K, Tada N, Mochizuki S, Nagano M. Source: Intern Med. 1992 January; 31(1): 69-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1568046
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A monoclonal antibody to the alpha2 domain of murine major histocompatibility complex class I that specifically kills activated lymphocytes and blocks liver damage in the concanavalin A hepatitis model. Author(s): Matsuoka S, Tsurui H, Abe M, Terashima K, Nakamura K, Hamano Y, Ohtsuji M, Honma N, Serizawa I, Ishii Y, Takiguchi M, Hirose S, Shirai T. Source: The Journal of Experimental Medicine. 2003 August 4; 198(3): 497-503. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885869
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A study on the relationship of porphyria cutanea tarda and liver damage. Author(s): Horkay I, Prekopa A, Dalmy L, Dan S, Tamasi P. Source: Arch Dermatol Forsch. 1973 September 19; 247(3): 235-43. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4748769
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A syndrome of liver damage and intravascular coagulation in the last trimester of normotensive pregnancy. A clinical and histopathological study. Author(s): Hague WM, de Swiet M. Source: British Journal of Obstetrics and Gynaecology. 1986 October; 93(10): 1113-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3790477
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A syndrome of liver damage and intravascular coagulation in the last trimester of normotensive pregnancy. A clinical and histopathological study. Author(s): Aarnoudse JG, Houthoff HJ, Weits J, Vellenga E, Huisjes HJ. Source: British Journal of Obstetrics and Gynaecology. 1986 February; 93(2): 145-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3511956
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A thromboxane A2 synthetase inhibitor, OKY-046, reduces liver damage in hepatectomy. Author(s): Shimada M, Matsumata T, Shirabe K, Sugimachi K. Source: Surgery. 1993 November; 114(5): 993-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8236027
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Absence of anti-trifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage. Author(s): Sakaguchi Y, Inaba S, Irita K, Sakai H, Nawata H, Takahashi S. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1994 May; 41(5 Pt 1): 398-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8055607
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Accidental intoxication with methylene dianiline p,p'-diaminodiphenylmethane: acute liver damage after presumed ecstasy consumption. Author(s): Tillmann HL, van Pelt FN, Martz W, Luecke T, Welp H, Dorries F, Veuskens A, Fischer M, Manns MP. Source: Journal of Toxicology. Clinical Toxicology. 1997; 35(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9022650
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Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. Author(s): Carlson JA, Rogers BB, Sifers RN, Finegold MJ, Clift SM, DeMayo FJ, Bullock DW, Woo SL. Source: The Journal of Clinical Investigation. 1989 April; 83(4): 1183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2784798
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Acute liver damage and ecstasy ingestion. Author(s): Ellis AJ, Wendon JA, Portmann B, Williams R. Source: Gut. 1996 March; 38(3): 454-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8675102
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Acute liver damage possibly related to sertraline and venlafaxine ingestion. Author(s): Kim KY, Hwang W, Narendran R. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10200868
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Acute liver damage with characteristic apoptotic hepatocytes by ingestion of Aplysia kurodai, a sea hare. Author(s): Sakamoto Y, Nakajima T, Misawa S, Ishikawa H, Itoh Y, Nakashima T, Okanoue T, Kashima K, Tsuji T. Source: Intern Med. 1998 November; 37(11): 927-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9868953
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Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement? Author(s): Croft AM, Herxheimer A. Source: Bmc Public Health [electronic Resource]. 2002 March 25; 2(1): 6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914150
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Aflatoxin and liver damage with encephalopathy. Author(s): Dvorackova I, Zilkova J, Brodsky F, Cerman J. Source: Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove. 1972; 15(4): 521-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4526185
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Agranulocytosis and liver damage associated with pyrazinobutazone with evidence for an immunological mechanism. Author(s): Maria VA, da Silva JA, Victorino RM. Source: The Journal of Rheumatology. 1989 November; 16(11): 1484-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2600947
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Alcohol and liver damage. Author(s): Sherlock S. Source: Acta Med Port. 1981; (Suppl 2): 49-58. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7234499
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Alcohol and nutrition: caloric value, bioenergetics, and relationship to liver damage. Author(s): Mitchell MC, Herlong HF. Source: Annual Review of Nutrition. 1986; 6: 457-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3015171
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Alcoholic liver damage--toxicity, autoimmunity and allergy. Author(s): Sheron N. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1994 June; 24(6): 503-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7922769
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Alcohol-induced bone disease in the absence of severe chronic liver damage. Author(s): Diez A, Puig J, Serrano S, Marinoso ML, Bosch J, Marrugat J, Mellibovsky L, Nogues X, Knobel H, Aubia J. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1994 June; 9(6): 825-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8079658
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Alcohol-induced brain damage and liver damage in young males. Author(s): Lee K, Moller L, Hardt F, Haubek A, Jensen E. Source: Lancet. 1979 October 13; 2(8146): 759-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=90858
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Allopurinol-hypersensitivity vasculitis and liver damage. Author(s): Boyer TD, Sun N, Reynolds TB. Source: The Western Journal of Medicine. 1977 February; 126(2): 143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=139760
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Alpha-fetoprotein-lectin binding as a marker of tumour activity or liver damage. Author(s): Marrink J, Sleijfer DT, de Vries EG, Schraffordt Koops H. Source: European Journal of Cancer (Oxford, England : 1990). 1990; 26(9): 969-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1703772
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Alterations of ATP levels and of energy parameters in the blood of alcoholic and nonalcoholic patients with liver damage. Author(s): Hernandez-Munoz R, Glender W, Diaz-Munoz M, Suarez J, Lozano J, Chagoya de Sanchez V. Source: Alcoholism, Clinical and Experimental Research. 1991 June; 15(3): 500-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1877735
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Amodiaquine induced agranulocytosis and liver damage. Author(s): Neftel KA, Woodtly W, Schmid M, Frick PG, Fehr J. Source: British Medical Journal (Clinical Research Ed.). 1986 March 15; 292(6522): 721-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3082410
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Anicteric liver damage during nitrofurantoin medication. Author(s): Klemola H, Penttila O, Runeberg L, Tallqvist G. Source: Scandinavian Journal of Gastroenterology. 1975; 10(5): 501-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1153946
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Antibodies to hepatocyte derived antigens and liver damage in patients after bone marrow transplantation. Author(s): Borzi RM, Meliconi R, Conte R, Bandini G, Ricci P, Miglio F, Facchini A, Gasbarrini G. Source: Allergologia Et Immunopathologia. 1991 March-April; 19(2): 63-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1772106
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Apparent “inhibition” as tested by means of the dilution curve system in patients with clotting defect due to liver damage. Author(s): Girolami A, Dal Bo Zanon R, Sticchi A. Source: Blut. 1977 September 29; 35(3): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=912109
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Association of restriction fragment length polymorphism in alcohol dehydrogenase 2 gene with alcohol induced liver damage. Author(s): Sherman DI, Ward RJ, Warren-Perry M, Williams R, Peters TJ. Source: Bmj (Clinical Research Ed.). 1993 November 27; 307(6916): 1388-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7903883
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Autoimmunity to a liver membrane lipoprotein and liver damage in alcoholic liver disease. Author(s): Perperas A, Tsantoulas D, Portmann B, Eddleston AL, Williams R. Source: Gut. 1981 February; 22(2): 149-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7215946
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Benign bile duct tumours, non-parasitic liver cysts and liver damage in males. Author(s): Karhunen PJ, Penttila A, Liesto K, Mannikko A, Mottonen M. Source: Journal of Hepatology. 1986; 2(1): 89-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3950364
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By the way, doctor. My neighbor takes something called milk thistle. He likes to drink alcohol and believes the herb will protect him against any kind of liver damage. Is he right? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2001 July; 26(9): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511452
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Carbimazole hypersensitivity and liver damage. Author(s): Jenkins RM, Evans DM. Source: Br J Clin Pract. 1981 November-December; 35(11-12): 415-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7306451
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Catecholamines in the plasma and urine of patients with alcoholic liver damage under resting and exercise conditions. Author(s): Ratge D, Brugger G, Wehr M, Bode JC, Wisser H. Source: J Clin Chem Clin Biochem. 1985 August; 23(8): 447-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4056661
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Causes and effects of acute liver damage. Author(s): Sherlock S. Source: Scandinavian Journal of Gastroenterology. Supplement. 1970; 6: 187-202. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4917496
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Changes in activation of aspartate aminotransferase by pyridoxal 5'-phosphate after experimental liver damage in rabbits. Author(s): de Waal A, le Roux S, Potgieter GM, Barnard HC, Schoombie EM. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1982 July 15; 122(3): 395-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7105422
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Changes in superoxide anion production in neutrophils from multitransfused betathalassemia patients: correlation with ferritin levels and liver damage. Author(s): de Martino M, Rossi ME, Resti M, Vullo C, Vierucci A. Source: Acta Haematologica. 1984; 71(5): 289-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6331044
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Characterization of complement-mediated liver damage and protection in control and transgenic mice for human complement blockers MCP and DAF. Author(s): Mulder LC, Mora M, Lazzeri M, Boschi M, Ciccopiedi E, Marinucci G, Melli CM, Bruzzone P, Alfani D, Cortesini R, Rossini M. Source: Transplantation Proceedings. 1996 February; 28(1): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8644143
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Chronic excessive acetaminophen use and liver damage. Author(s): Barker JD Jr, de Carle DJ, Anuras S. Source: Annals of Internal Medicine. 1977 September; 87(3): 299-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=900673
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Chronic hepatitis C, ibuprofen, and liver damage. Author(s): Andrade RJ, Lucena MI, Garcia-Cortes M, Garcia-Ruiz E, Fernandez-Bonilla E, Vazquez L. Source: The American Journal of Gastroenterology. 2002 July; 97(7): 1854-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135061
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Clinical evaluation of measurement of serum guanase activity as a screening test of liver damage. Author(s): Ito S, Takaoka T, Hirano H, Kishi S, Mori H. Source: Gastroenterol Jpn. 1981; 16(5): 478-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7327386
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Clinical implications of salicylate-induced liver damage. Author(s): Levy G, Yaffe SJ. Source: Am J Dis Child. 1975 December; 129(12): 1385-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1199979
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Clinical trial of CDP-choline as a medicament for acute pancreatitis and its relation to pancreas and liver damage in acute pancreatitis. Author(s): Ozawa K, Kitamura O, Uchida K, Honjo I. Source: Bull Soc Int Chir. 1974 September-December; 33(5-6): 483-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4156196
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Clinico-pathologic correlation of liver damage in patients treated with 6mercaptopurine and Adriamycin. Author(s): Minow RA, Stern MH, Casey JH, Rodriguez V, Luna MA. Source: Cancer. 1976 October; 38(4): 1524-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1068739
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Co-infection with several HCV genotypes enhances liver damage in patients with chronic hepatitis C. The Hepatitis/HIV Spanish Study Group. Author(s): Soriano V, Bravo R, Garcia-Samaniego J, Castilla J, Castro A, Carballo E, Gonzalez-Anglada I, Moreno A. Source: The Journal of Infection. 1997 September; 35(2): 202-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9354365
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Color ultrasound-guided fine needle cutting biopsy for the characterization of diffuse liver damage in critical bone marrow transplanted patients. Author(s): Picardi M, Muretto P, De Rosa G, Selleri C, De Renzo A, Persico M, Rotoli B. Source: Haematologica. 2002 June; 87(6): 652-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031923
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Comfrey and liver damage. Author(s): Roitman JN. Source: Lancet. 1981 April 25; 1(8226): 944. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6112346
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Comparative studies on the clinical value of serum quinineoxidase, transaminase and sorbitoldehydrogenase determination for the demonstration of liver damage in biliary calculosis. Author(s): Genov D, Milev M. Source: Nauchni Tr Vissh Med Inst Sofiia. 1969; 48(2): 7-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4245256
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Competition in liver transport between chenodeoxycholic acid and ursodeoxycholic acid as a mechanism for ursodeoxycholic acid and its amidates' protection of liver damage induced by chenodeoxycholic acid. Author(s): Piazza F, Montagnani M, Russo C, Azzaroli F, Aldini R, Roda E, Roda A. Source: Dig Liver Dis. 2000 May; 32(4): 318-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11515630
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Congenital hepatic fibrosis with fatal cholestatic liver damage. Author(s): Takatori M, Iwabuchi S, Hayashi T, Takahashi Y, Suzuki M, Iino S, Maeyama S, Uchikoshi T. Source: Intern Med. 2000 November; 39(11): 930-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11065245
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Congenital liver damage after treatment of mother with valproic acid and phenytoin? Author(s): Felding I, Rane A. Source: Acta Paediatr Scand. 1984 July; 73(4): 565-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6431746
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Consumption of alcohol in the presence of hepatitis C virus is an additive risk for liver damage. Author(s): Ohta S, Watanabe Y, Nakajima T. Source: Preventive Medicine. 1998 May-June; 27(3): 461-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9612837
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Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. Author(s): Lindh M, Hannoun C, Dhillon AP, Norkrans G, Horal P. Source: The Journal of Infectious Diseases. 1999 April; 179(4): 775-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10068571
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Correlation between liver damage and degree of gastric mucose colonization by Helicobacter pylori in subjects with parenchymatous liver damage. Author(s): Stalke P, Zoltowska A, Orlowski M, Ellert-Zygadlowska J, WitczakMalinowska K, Michalska Z, Lakomy EA, Trocha H, Stepinski J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 May; 7 Suppl 1: 271-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211735
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Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Author(s): Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, Grippon P, Hoang C, Valla D, Piette JC, et al. Source: Gastroenterology. 1994 May; 106(5): 1291-300. Erratum In: Gastroenterology 1995 February; 108(2): 620. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7513667
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Cytosine arabinoside induced liver damage: histopathologic demonstration. Author(s): Pizzuto J, Aviles A, Ramos E, Cervera J, Aguirre J. Source: Medical and Pediatric Oncology. 1983; 11(4): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6577264
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Dacarbazine (DTIC)-induced human liver damage light and electron-microscopic findings. Author(s): Dancygier H, Runne U, Leuschner U, Milbradt R, Classen M. Source: Hepatogastroenterology. 1983 June; 30(3): 93-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6884975
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Danazol and liver damage. Author(s): Pearson K, Zimmerman HJ. Source: Lancet. 1980 March 22; 1(8169): 645-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6102641
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Delayed onset of severe hepatitis C-related liver damage following liver transplantation: a matter of concern? Author(s): Berenguer M, Aguilera V, Prieto M, Carrasco D, Rayon M, San Juan F, Landaverde C, Mir J, Berenguer J. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 November; 9(11): 1152-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586875
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Diagnostic accuracy of helical CT arterial portography and CT hepatic arteriography for hypervascular hepatocellular carcinoma in chronic liver damage. An ROC analysis. Author(s): Makita O, Yamashita Y, Arakawa A, Nakayama Y, Mitsuzaki K, Ando M, Namimoto T, Takahashi M. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2000 September; 41(5): 464-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11016767
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Different reactivity against HCV proteins (RIBA 3) according to progression of liver damage. Author(s): Barbacini IG, Goldoni E, De Sanctis GM, Margiotta MC, Sebastiano D, D'Errico DA, Altavilla N, Magnapera A, Rivanera D, Lilli D, Ippoliti F, Grimaldi F, Mancini C, Chircu LV. Source: Panminerva Medica. 1998 December; 40(4): 269-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973819
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Dimethylformamide-induced liver damage among synthetic leather workers. Author(s): Wang JD, Lai MY, Chen JS, Lin JM, Chiang JR, Shiau SJ, Chang WS. Source: Archives of Environmental Health. 1991 May-June; 46(3): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2039271
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Disorderd hemostasis in liver damage from paracetamol overdose. Author(s): Clark R, Borirakchanyavat V, Gazzard BG, Rake MO, Shilkin KB, Flute PT, Williams R. Source: Gastroenterology. 1973 November; 65(5): 788-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4758975
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Disseminated intravascular coagulation in lupus erythematosus with acute liver damage. Author(s): Shimamoto Y, Sano M, Kaneda S, Tsunada S, Yamamoto K, Yamaguchi M. Source: Intern Med. 1992 December; 31(12): 1392-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1300175
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Disseminated intravascular coagulation with renal and liver damage as the predominant manifestations of recurrent relapses in systemic juvenile rheumatoid arthritis. Author(s): Schwartz D, Averbuch M, Pines A, Kornovsky R, Levo Y. Source: Annals of the Rheumatic Diseases. 1992 March; 51(3): 347-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1575579
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Disseminated intravascular coagulation, uremia and liver damage after intravenous crude opium. Author(s): Bernheim JL, ten Cate JW, van der Heide RM. Source: Acta Med Scand. 1972 January-February; 191(1-2): 63-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5032439
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Disturbances in glucose metabolism in patients with liver damage due to paracetamol overdose. Author(s): Record CO, Chase RA, Alberti KG, Williams R. Source: Clin Sci Mol Med. 1975 November; 49(5): 473-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1192705
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Disturbances of lactate metabolism in patients with liver damage due to paracetamol overdose. Author(s): Record CO, Chase RA, Williams R, Appleton D. Source: Metabolism: Clinical and Experimental. 1981 July; 30(7): 638-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7242370
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Down-regulation of Fas-L in glioma cells by ribozyme reduces cell apoptosis, tumourinfiltrating cells, and liver damage but accelerates tumour formation in nude mice. Author(s): Chio CC, Wang YS, Chen YL, Lin SJ, Yang BC. Source: British Journal of Cancer. 2001 October 19; 85(8): 1185-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11710833
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Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Author(s): Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, Saveria Croce L, Sasso F, Pozzato G, Cristianini G, Brandi G. Source: Gut. 1997 December; 41(6): 845-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9462221
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Drug-induced liver damage -- a three-year study of patients from one gastroenterological department. Author(s): Hartleb M, Biernat L, Kochel A. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 April; 8(4): Cr292-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11951073
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Effect of high fiber vegetable-fruit diet on the activity of liver damage and serum iron level in porphyria cutanea tarda (PCT). Author(s): Dabrowska E, Jablonska-Kaszewska I, Falkiewicz B. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 May; 7 Suppl 1: 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211737
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Effect of liver damage on the level of coagulation factor II, X and VII in human and bovine plasma. Author(s): Rybak M, Dyrhon V, Losticky C, Dyrhonova V, Valenta Z. Source: Thrombosis Research. 1988 October 15; 52(2): 79-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3194893
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Effect of liver damage on the pharmacokinetics of dexamethasone. Author(s): Kutemeyer S, Schurmeyer TH, von zur Muhlen A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1994 December; 131(6): 594-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7804441
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Effects of ursodeoxycholic acid (UDCA) on serum liver damage indices in patients with chronic active hepatitis. A double-blind controlled study. Author(s): Rolandi E, Franceschini R, Cataldi A, Cicchetti V, Carati L, Barreca T. Source: European Journal of Clinical Pharmacology. 1991; 40(5): 473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1679391
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Effects of vitamin E on toxicoderma associated with liver damage. Case report. Author(s): Fujii T. Source: The Keio Journal of Medicine. 1972 June; 21(2): 105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4347360
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Efficacy and safety of a prothrombin complex concentrate with two virus-inactivation steps in patients with severe liver damage. Author(s): Lorenz R, Kienast J, Otto U, Egger K, Kiehl M, Schreiter D, Kwasny H, Haertel S, Barthels M. Source: European Journal of Gastroenterology & Hepatology. 2003 January; 15(1): 15-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544689
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Electroimmunoassay of factor IX in patients with liver damage and vitamin K unresponsive coagulation disorder. Author(s): Girolami A, Burul A, Cappellato G, Dal Bo Zanon R. Source: Folia Haematol Int Mag Klin Morphol Blutforsch. 1979; 106(1): 65-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=88391
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Elevated serum gamma-glutamyl-transferase (transpeptidase) and histological liver damage in alcoholism. Author(s): Wu A, Slavin G, Levi AJ. Source: The American Journal of Gastroenterology. 1976 April; 65(4): 318-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7137
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Enhancement of hepatitis C virus replication and liver damage in HIV-coinfected patients on antiretroviral combination therapy. Author(s): Vento S, Garofano T, Renzini C, Casali F, Ferraro T, Concia E. Source: Aids (London, England). 1998 January 1; 12(1): 116-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9456265
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Esophageal varices: diagnosis with gadolinium-enhanced MR imaging of the liver for patients with chronic liver damage. Author(s): Matsuo M, Kanematsu M, Kim T, Hori M, Takamura M, Murakami T, Kondo H, Moriyama N, Nakamura H, Hoshi H. Source: Ajr. American Journal of Roentgenology. 2003 February; 180(2): 461-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540452
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Ethanol metabolism, oxygen availability and alcohol induced liver damage. Author(s): Israel Y, Kalant H, Khanna JM, Orrego H, Phillips MJ, Stewart DJ. Source: Advances in Experimental Medicine and Biology. 1977; 85A: 343-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=920490
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Ethylesterases as indicators of liver damage. I. Studies on malathion carboxylesterases. Author(s): Talcott RE, Pond SM, Ketterman A, Becker CE. Source: Toxicology and Applied Pharmacology. 1982 August; 65(1): 69-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7147257
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Evaluation of phenyl acetate esterase activity as an index of liver damage. Author(s): Takahashi Y, Aoyama I, Ito F, Yamamura Y. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1967 October; 18(1): 21-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6064689
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Evidence against the role of hepatitis C virus in severe liver damage occurring early in the course of acute leukemia in children. Author(s): Locasciulli A, Pontisso P, Cavalletto D, Fraschini D, Uderzo C, Masera G, Alberti A. Source: Leukemia & Lymphoma. 1994 March; 13(1-2): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7517743
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Evidence of liver damage by toxin from a bloom of the blue-green alga, Microcystis aeruginosa. Author(s): Falconer IR, Beresford AM, Runnegar MT. Source: The Medical Journal of Australia. 1983 May 28; 1(11): 511-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6405136
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Factors determining liver damage in chronic alcoholics. Author(s): Eghoje KN, Juhl E. Source: Scandinavian Journal of Gastroenterology. 1973; 8(6): 505-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4772204
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Fatal deterioration of neurological disease after orthotopic liver transplantation for valproic acid-induced liver damage. Author(s): Kayihan N, Nennesomo I, Ericzon BG, Nemeth A. Source: Pediatric Transplantation. 2000 August; 4(3): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933322
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Fatty acid composition of liver total lipids in alcoholic patients with and without liver damage. Author(s): de la Maza MP, Hirsch S, Nieto S, Petermann M, Bunout D. Source: Alcoholism, Clinical and Experimental Research. 1996 November; 20(8): 1418-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8947319
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Flucloxacillin-associated liver damage. Author(s): Lobatto S, Dijkmans BA, Mattie H, Van Hooff JP. Source: The Netherlands Journal of Medicine. 1982; 25(2): 47-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7070561
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Flucloxacillin-induced cholestatic liver damage. Author(s): Bengtsson F, Floren CH, Hagerstrand I, Soderstrom C, Aberg T. Source: Scandinavian Journal of Infectious Diseases. 1985; 17(1): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3992199
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Four cases of acute liver damage following the ingestion of a sea hare egg. Author(s): Hino K, Mitsui Y, Hirano Y. Source: Journal of Gastroenterology. 1994 October; 29(5): 679. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8000522
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Frequency of renal impairment in paracetamol overdose compared with other causes of acute liver damage. Author(s): Wilkinson SP, Moodie H, Arroyo VA, Williams R. Source: Journal of Clinical Pathology. 1977 February; 30(2): 141-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=845262
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Full and empty Dane particles in chronic hepatitis B virus infection: relation to hepatitis B e antigen and presence of liver damage. Author(s): Alberti A, Diana S, Scullard GH, Eddleston WF, Williams R. Source: Gastroenterology. 1978 November; 75(5): 869-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=700329
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Functional liver damage during laparoscopic cholecystectomy as the sign of the late common bile duct stricture development. Author(s): Hochstadetr H, Bekavac-Beslin M, Doko M, Kopljar M, Cupic H, Glavan E, Mijic A, Zovak M, Salic D. Source: Hepatogastroenterology. 2003 May-June; 50(51): 676-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828058
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Gadolinium-enhanced MR imaging of the liver: optimizing imaging delay for hepatic arterial and portal venous phases--a prospective randomized study in patients with chronic liver damage. Author(s): Kanematsu M, Semelka RC, Matsuo M, Kondo H, Enya M, Goshima S, Moriyama N, Hoshi H. Source: Radiology. 2002 November; 225(2): 407-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409573
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Genetic determinants of ethanol-induced liver damage. Author(s): Monzoni A, Masutti F, Saccoccio G, Bellentani S, Tiribelli C, Giacca M. Source: Molecular Medicine (Cambridge, Mass.). 2001 April; 7(4): 255-62. Erratum In: Mol Med 2001 December; 7(12): 861. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11471570
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Glucose turnover rate and peripheral insulin sensitivity in alcoholic patients without liver damage. Author(s): Bunout D, Petermann M, Bravo M, Kelly M, Hirsch S, Ugarte G, Iturriaga H. Source: Annals of Nutrition & Metabolism. 1989; 33(1): 31-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2662885
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Gut-liver axis: a new point of attack to treat chronic liver damage? Author(s): Loguercio C, De Simone T, Federico A, Terracciano F, Tuccillo C, Di Chicco M, Carteni M. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2144-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190198
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Halothane anaesthesia and liver damage. Author(s): Neuberger J, Williams R. Source: British Medical Journal (Clinical Research Ed.). 1984 October 27; 289(6452): 11369. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6435802
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Halothane and liver damage. Author(s): Skulberg A, Endresen GK, Lund I. Source: J Oslo City Hosp. 1970 January; 20(1): 3-16. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5434335
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Halothane and liver damage. Author(s): Trey C, Lipworth L, Davidson CS. Source: The New England Journal of Medicine. 1969 March 6; 280(10): 562-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5764462
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Halothane and liver damage. Author(s): Allen HL. Source: The New England Journal of Medicine. 1969 March 6; 280(10): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5764461
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Halothane and liver damage. Author(s): Lorhan PH. Source: The New England Journal of Medicine. 1969 March 6; 280(10): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5764460
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Halothane and liver damage. Author(s): Stephen CR. Source: The New England Journal of Medicine. 1969 March 6; 280(10): 561-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5764459
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Halothane and liver damage. Author(s): Rosenak D, Halevy A, Orda R. Source: Postgraduate Medical Journal. 1989 March; 65(761): 129-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2682584
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Halothane induced liver damage. Author(s): Lund I, Skulberg A. Source: J Oslo City Hosp. 1973 October; 23(10): 157-66. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4775526
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Halothane-associated liver damage and renal failure in a young child. Author(s): Hals J, Dodgson MS, Skulberg A, Kenna JG. Source: Acta Anaesthesiologica Scandinavica. 1986 November; 30(8): 651-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3811809
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Halothane-induced liver damage: an analysis of the material reported to the Swedish Adverse Drug Reaction Committee, 1966-1973. Author(s): Bottiger LE, Dalen E, Hallen B. Source: Acta Anaesthesiologica Scandinavica. 1976; 20(1): 40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1266555
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Halothane-induced liver damage--an entity. Author(s): Combes B. Source: The New England Journal of Medicine. 1969 March 6; 280(10): 558-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5764456
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HBV cccDNA in patients' sera as an indicator for HBV reactivation and an early signal of liver damage. Author(s): Chen Y, Sze J, He ML. Source: World Journal of Gastroenterology : Wjg. 2004 January; 10(1): 82-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695774
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HBV DNA level and antigen concentration in evaluating liver damage of patients with chronic hepatitis B. Author(s): Xie Y, Zhao H, Dai WS, Xu DZ. Source: Hepatobiliary Pancreat Dis Int. 2003 August; 2(3): 418-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599951
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Hepatic injury and drug metabolism in patients with alpha-methyldopa-induced liver damage. Author(s): Sotaniemi EA, Hokkanen OT, Ahokas JT, Pelkonen RO, Ahlqvist J. Source: European Journal of Clinical Pharmacology. 1977 December 28; 12(6): 429-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=598417
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Hepatitis and liver damage among patients and staff in a transplantation unit. Author(s): Franksson C. Source: Transplantation Proceedings. 1969 March; 1(1): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4944220
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Hepatitis B virus and alcoholic liver damage in the Airin district. (Osaka's skid row area). Author(s): Monna T, Kawa M, Asai H, Kim K, Harihara S, Kuroki T, Yamamoto S. Source: Gastroenterol Jpn. 1980 April; 15(2): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6155305
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Hepatitis B virus carriers without precore mutations in hepatitis B e antigen-negative stage show more severe liver damage. Author(s): Lindh M, Horal P, Dhillon AP, Furuta Y, Norkrans G. Source: Hepatology (Baltimore, Md.). 1996 September; 24(3): 494-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8781313
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Hepatitis C viral quasispecies and liver damage in patients with chronic hepatitis C virus infection. Author(s): Hayashi J, Kishihara Y, Yamaji K, Furusyo N, Yamamoto T, Pae Y, Etoh Y, Ikematsu H, Kashiwagi S. Source: Hepatology (Baltimore, Md.). 1997 March; 25(3): 697-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9049221
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Hepatitis C virus core protein leads to immune suppression and liver damage in a transgenic murine model. Author(s): Soguero C, Joo M, Chianese-Bullock KA, Nguyen DT, Tung K, Hahn YS. Source: Journal of Virology. 2002 September; 76(18): 9345-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186917
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Hepatitis C virus-related liver damage is related to cold activation of complement. Author(s): Nomura H, Ogo T, Rikimaru N, Ueno S, Kakuno T, Okamoto O, Shiraishi G, Kashiwagi S. Source: Journal of Clinical Gastroenterology. 1997 October; 25(3): 529-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9412971
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Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: the role of etiology, disease activity, iron, and lipid peroxidation. Author(s): Farinati F, Cardin R, D'Errico A, De Maria N, Naccarato R, Cecchetto A, Grigioni W. Source: Hepatology (Baltimore, Md.). 1996 June; 23(6): 1468-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8675166
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High serum cholestanol and low campesterol/sitosterol ratio indicate severe liver damage and liver transplantation in primary biliary cirrhosis. Author(s): Nikkila K, Hockerstedt K, Miettinen TA. Source: Transplantation Proceedings. 1992 February; 24(1): 383-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1539326
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High-dose methotrexate administration and acute liver damage in children treated for acute lymphoblastic leukemia. A prospective study. Author(s): Locasciulli A, Mura R, Fraschini D, Gornati G, Scovena E, Gervasoni A, Uderzo C, Masera G. Source: Haematologica. 1992 January-February; 77(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1398282
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Histaminase level changes in liver damage. Author(s): Guha TK, Charkravarti HS, Basu A, Bannerjee S, Lahiri SC. Source: Res Commun Chem Pathol Pharmacol. 1973 May; 5(3): 843-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4633771
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HLA class II favors clearance of HCV infection and progression of the chronic liver damage. Author(s): Mangia A, Gentile R, Cascavilla I, Margaglione M, Villani MR, Stella F, Modola G, Agostiano V, Gaudiano C, Andriulli A. Source: Journal of Hepatology. 1999 June; 30(6): 984-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10406174
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Host immune response and variations in the virus genome: pathogenesis of liver damage caused by hepatitis B virus. Author(s): Naoumov NV, Eddleston AL. Source: Gut. 1994 August; 35(8): 1013-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7926896
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Hypermetabolic state and hypoxic liver damage. Author(s): Israel Y, Orrego H. Source: Recent Dev Alcohol. 1984; 2: 119-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6328588
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Hypothyroidism and thyroxine-induced liver damage. Author(s): Wiener JD. Source: Clinical Endocrinology. 1990 January; 32(1): 135. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2331810
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I take Zocor for high cholesterol. My doctor checks my lipid levels every six months and they have been pretty good for a few years now. But he also checks my liverfunction tests, because liver damage is one of the side effects of this drug. How worried should I be about this problem, and is checking my liver tests every six months often enough? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 1998 September; 9(1): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9734250
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Immune-mediated liver damage in chronic hepatitis C. Author(s): Wejstal R. Source: Scandinavian Journal of Gastroenterology. 1995 July; 30(7): 609-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7481520
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Immunoglobulin on the surface of isolated hepatocytes is associated with antibodydependent cell-mediated cytotoxicity and liver damage. Author(s): Vergani D, Mieli-Vergani G, Mondelli M, Portmann B, Eddleston AL. Source: Liver. 1987 December; 7(6): 307-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3437792
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Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation. Author(s): McCaughan GW, Zekry A. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 November; 9(11): S21-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586891
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Increased serum gamma-glutamyltransferase activity in renal transplant recipients: liver damage or microsomal enzyme induction? Author(s): Jung K, Scholz D. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1984 August 15; 141(1): 1-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6147212
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Inhalation anaesthetics and liver damage. Author(s): Lee NC. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1993 November; Suppl: 1-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7839181
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Intravenous immunoglobulin prophylaxis causing liver damage in 16 of 77 patients with hypogammaglobulinemia or IgG subclass deficiency. Author(s): Bjorkander J, Cunningham-Rundles C, Lundin P, Olsson R, Soderstrom R, Hanson LA. Source: The American Journal of Medicine. 1988 January; 84(1): 107-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3122562
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Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. Author(s): Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, Krammer PH, Runkel L. Source: The Journal of Experimental Medicine. 1995 November 1; 182(5): 1223-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7595193
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Irreversible liver damage after azathioprine. Author(s): Zarday Z, Veith FJ, Gliedman ML, Soberman R. Source: Jama : the Journal of the American Medical Association. 1972 November 6; 222(6): 690-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4562099
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Isolated liver damage in chemical workers. Author(s): Dossing M, Ranek L. Source: Br J Ind Med. 1984 February; 41(1): 142-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6691931
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Ketoconazole-induced liver damage. Author(s): Findor JA, Sorda JA, Igartua EB, Avagnina A. Source: Medicina (B Aires). 1998; 58(3): 277-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9713096
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Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage. Author(s): Keshavarzian A, Holmes EW, Patel M, Iber F, Fields JZ, Pethkar S. Source: The American Journal of Gastroenterology. 1999 January; 94(1): 200-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9934756
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Liver damage after danazol and glucocorticoids for chronic idiopathic thrombocytopenic purpura (ITP) Author(s): Sakuma A, Tsuboi I, Morimoto K, Sawada U, Horie T. Source: Intern Med. 1995 January; 34(1): 69. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7718987
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Liver damage after halothane anaesthesia: analysis of cases in Finnish hospitals in 1972-1981. Author(s): Oikkonen M, Rosenberg PH. Source: Ann Chir Gynaecol. 1984; 73(1): 28-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6732154
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Liver damage after transarterial chemoembolization without embolizing agent in unresectable hepatocellular carcinoma. Author(s): Puleo S, Mauro L, Gagliano G, Lombardo R, Li Destri G, Petrillo G, Di Carlo I. Source: Tumori. 2003 May-June; 89(3): 285-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908784
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Liver damage and protective effect of high density lipoprotein cholesterol. Author(s): Salonen JT. Source: Bmj (Clinical Research Ed.). 2003 November 8; 327(7423): 1082-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604929
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Liver damage as a potential source of error in the estimation of myocardial infarct size from plasma creatine kinase activity. Author(s): Oostenbroek RJ, Willems GM, Boumans ML, Soeters PB, Hermens WT. Source: Cardiovascular Research. 1985 February; 19(2): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3978666
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Liver damage associated with fansidar. Author(s): Wejstal R, Lindberg J, Malmvall BE, Norkrans G. Source: Lancet. 1986 April 12; 1(8485): 854-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2870335
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Liver damage caused by therapeutic vitamin A administration: estimate of doserelated toxicity in 41 cases. Author(s): Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C. Source: Gastroenterology. 1991 June; 100(6): 1701-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2019375
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Liver damage due to free radicals. Author(s): Poli G. Source: British Medical Bulletin. 1993 July; 49(3): 604-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8221026
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Liver damage during interferon therapy for chronic myeloid leukaemia. Author(s): Philippe P, Fialip J, Souweine B, Aumaitre O, Marcheix JC, Lavarenne J. Source: Eur J Med. 1993 August-September; 2(7): 446. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8258041
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Liver damage from flucloxacillin, cloxacillin and dicloxacillin. Author(s): Olsson R, Wiholm BE, Sand C, Zettergren L, Hultcrantz R, Myrhed M. Source: Journal of Hepatology. 1992 May; 15(1-2): 154-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1506634
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Liver damage from low-dose oral contraceptives. Author(s): Lindgren A, Olsson R. Source: Journal of Internal Medicine. 1993 September; 234(3): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8354979
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Liver damage from verapamil. Author(s): Guarascio P, D'Amato C, Sette P, Conte A, Visco G. Source: British Medical Journal (Clinical Research Ed.). 1984 February 4; 288(6414): 3623. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6419928
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Liver damage in disorders of iron overload. A hypothesis. Author(s): Wheby MS. Source: Archives of Internal Medicine. 1984 March; 144(3): 621-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6703832
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Liver damage in human small intestinal bacterial overgrowth. Author(s): Riordan SM, McIver CJ, Williams R. Source: The American Journal of Gastroenterology. 1998 February; 93(2): 234-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9468250
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Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection. Author(s): Piperno A, Fargion S, D'Alba R, Roffi L, Fracanzani AL, Vecchi L, Failla M, Fiorelli G. Source: Journal of Hepatology. 1992 November; 16(3): 364-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1487615
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Liver damage in juvenile inflammatory bowel disease. Author(s): Nemeth A, Ejderhamn J, Glaumann H, Strandvik B. Source: Liver. 1990 August; 10(4): 239-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2215095
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Liver damage in long-term anticonvulsant therapy: a serological and histological study. Author(s): Foster GR, Goldin RD, Freeth CJ, Nieman E, Oliveira DB. Source: The Quarterly Journal of Medicine. 1991 April; 79(288): 315-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1852857
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Liver damage in obese patients. Author(s): Del Gaudio A, Boschi L, Del Gaudio GA, Mastrangelo L, Munari D. Source: Obesity Surgery : the Official Journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. 2002 December; 12(6): 802-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12568185
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Liver damage in patients with colony-stimulating factor-producing tumors. Author(s): Suzuki A, Takahashi T, Okuno Y, Seko S, Fukuda Y, Nakamura K, Fukumoto M, Konaka Y, Imura H. Source: The American Journal of Medicine. 1993 February; 94(2): 125-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7679246
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Liver damage in patients with CSF-producing tumors. Author(s): Sadoff L, Davidson W. Source: The American Journal of Medicine. 1995 June; 98(6): 600-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7778581
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Liver damage in pharmaceutical industry workers. Author(s): Tomei F, Iavicoli S, Iavicoli A, Papaleo B, Baccolo TP. Source: Archives of Environmental Health. 1995 July-August; 50(4): 293-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7677429
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Liver damage preferentially results from CD8(+) T cells triggered by high affinity peptide antigens. Author(s): Russell JQ, Morrissette GJ, Weidner M, Vyas C, Aleman-Hoey D, Budd RC. Source: The Journal of Experimental Medicine. 1998 September 21; 188(6): 1147-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9743533
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Liver damage score--a new index for evaluation of the severity of chronic liver diseases. Author(s): Krastev Z. Source: Hepatogastroenterology. 1998 January-February; 45(19): 160-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9496507
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Liver damage with non-narcotic analgesics. Author(s): Prescott LF. Source: Med Toxicol. 1986; 1 Suppl 1: 44-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3547001
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Liver damage with reversible portal hypertension from vitamin A intoxication: demonstration of Ito cells. Author(s): Guarascio P, Portmann B, Visco G, Williams R. Source: Journal of Clinical Pathology. 1983 July; 36(7): 769-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6863568
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Liver damage, alcohol use, and diagnosis. Author(s): Sickora S, Slater E, Linn BS, Linn MW. Source: Int J Addict. 1983 July; 18(5): 753-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6629575
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Liver damage: mechanisms and management. Author(s): Sherman DI, Williams R. Source: British Medical Bulletin. 1994 January; 50(1): 124-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8149189
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Liver enzymes as predictors of liver damage due to blunt abdominal trauma in children. Author(s): Puranik SR, Hayes JS, Long J, Mata M. Source: Southern Medical Journal. 2002 February; 95(2): 203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846245
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Longitudinal measurement of methotrexate liver concentrations does not correlate with liver damage, clinical efficacy, or toxicity during a 3.5 year double blind study in rheumatoid arthritis. Author(s): Fathi NH, Mitros F, Hoffman J, Straniero N, Labreque D, Koehnke R, Furst DE. Source: The Journal of Rheumatology. 2002 October; 29(10): 2092-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12375317
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Magnetic resonance imaging as a screening procedure for methotrexate induced liver damage. Author(s): Rademaker M, Webb JA, Lowe DG, Meyrick-Thomas RH, Kirby JD, Munro DD. Source: The British Journal of Dermatology. 1987 September; 117(3): 311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3676081
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Malnutrition, liver damage, and cancer. Author(s): Grasso P. Source: Nutrition and Cancer. 1981; 3(2): 103-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7346790
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Management of acute liver damage in man. Author(s): Hoenig V. Source: Prog Liver Dis. 1970; 3: 269-81. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4908701
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Manifestations of chemically induced liver damage. Author(s): Batt AM, Ferrari L. Source: Clinical Chemistry. 1995 December; 41(12 Pt 2): 1882-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7497649
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Marker for liver damage in neonates born to mothers with HELLP syndrome. Author(s): Knapen M, van Schaijk F, Mulder T, Peters W, Steegers E. Source: Lancet. 1997 May 24; 349(9064): 1519-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9167466
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Mechanisms of liver damage. Author(s): Losser MR, Payen D. Source: Seminars in Liver Disease. 1996 November; 16(4): 357-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9027949
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Mechanisms of virally induced liver damage. Author(s): Lever AM. Source: Journal of Hepatology. 1987 June; 4(3): 399-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3598167
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Metabolism of steroids in fluorosis. 2. Oestrone loading test in male patients with fluorine liver damage. Author(s): Tokar VI, Potapenko OV, Naugolnikh EZ. Source: Acta Endocrinol (Copenh). 1971 April; 66(4): 694-701. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5108097
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Methotrexate maintenance therapy and liver damage in psoriasis. Author(s): van de Kerkhof PC, Hoefnagels WH, van Haelst UJ, Mali JW. Source: Clinical and Experimental Dermatology. 1985 May; 10(3): 194-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4006282
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Methotrexate, alcohol, and liver damage. Author(s): Almeyda J, Baker H, Levene GM, Barnardo D, Landells JW. Source: British Medical Journal. 1971 April 17; 2(754): 167. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5581500
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Methyldopa liver damage. Author(s): Toghill PJ, Smith PG, Benton P, Brown RC, Matthews HL. Source: British Medical Journal. 1974 August 31; 3(5930): 545-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4414663
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Monooxygenase enzyme activity in alcoholics with varying degrees of liver damage. Author(s): Hoensch H, Hartmann F, Schomerus H, Bieck P, Dolle W. Source: Gut. 1979 August; 20(8): 666-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=114458
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Morphologic alterations in patients with alpha-methyldopa-induced liver damage after short- and long-term exposure. Author(s): Arranto AJ, Sotaniemi EA. Source: Scandinavian Journal of Gastroenterology. 1981; 16(7): 853-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7323715
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Morphology of liver damage among polyvinyl chloride production workers. A report of 51 cases. Author(s): Gedigk P, Muller R, Bechtelsheimer H. Source: Annals of the New York Academy of Sciences. 1975 January 31; 246: 278-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1054962
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Multifactorial modeling, drug interactions, liver damage and aging. Author(s): Wosilait WD, Luecke RH. Source: General Pharmacology. 1988; 19(2): 143-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3280396
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Multiple endocrine abnormalities in a child with Blackfan-Diamond anemia and hemochromatosis. Significant improvement of growth velocity and predicted adult height following growth hormone treatment despite liver damage. Author(s): Lanes R, Muller A, Palacios A. Source: J Pediatr Endocrinol Metab. 2000 March; 13(3): 325-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10714760
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Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e seroconversion and its relation to liver damage in hepatitis B e antigen carriers. Author(s): Lindh M, Gustavson C, Mardberg K, Norkrans G, Dhillon AP, Horal P. Source: Journal of Medical Virology. 1998 July; 55(3): 185-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9624604
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Mutations and deletions in core promoter and precore stop codon in relation to viral replication and liver damage in Singaporean hepatitis B virus carriers. Author(s): Chen WN, Oon CJ. Source: European Journal of Clinical Investigation. 2000 September; 30(9): 787-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10998078
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Nadolol for lithium tremor in the presence of liver damage. Author(s): Dave M, Langbart MM. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1994 March; 6(1): 51-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7951646
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Natural killer cell activity in patients with liver cirrhosis relative to severity of liver damage. Author(s): Chuang WL, Liu HW, Chang WY, Chen SC, Hsieh MY, Wang LY. Source: Digestive Diseases and Sciences. 1991 March; 36(3): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1995265
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No significant correlation exists between core promoter mutations, viral replication, and liver damage in chronic hepatitis B infection. Author(s): Chun YK, Kim JY, Woo HJ, Oh SM, Kang I, Ha J, Kim SS. Source: Hepatology (Baltimore, Md.). 2000 November; 32(5): 1154-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050069
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Nonicteric liver damage with a gamma-glutamyl transpeptidase level of 5,609 units/l in a renal-transplant recipient receiving azathioprine. Author(s): Watanabe A, Obata T, Nagashima H, Sakagami K, Orita K. Source: Acta Medica Okayama. 1984 December; 38(6): 533-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6151783
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Nutrition and alcoholic liver damage. Author(s): Rao GA, Larkin EC. Source: Nutrition Reviews. 1989 February; 47(2): 63-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2633762
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Nutritional status of alcoholic patients: it's possible relationship to alcoholic liver damage. Author(s): Bunout D, Gattas V, Iturriaga H, Perez C, Pereda T, Ugarte G. Source: The American Journal of Clinical Nutrition. 1983 September; 38(3): 469-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6613916
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Occupational toxic liver damage. Author(s): Dossing M. Source: Journal of Hepatology. 1986; 3(1): 131-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3528279
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Ornidazole-induced liver damage: report of three cases and review of the literature. Author(s): Tabak F, Ozaras R, Erzin Y, Celik AF, Ozbay G, Senturk H. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003 October; 23(5): 351-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708896
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Oval cell hyperplasia in asparaginase--induced liver damage. Author(s): Zuckerman E, Misselevich I, Boss JH. Source: Liver. 2002 August; 22(4): 363-4. Erratum In: Liver 2002 October; 22(5): 439. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12296971
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Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics. Author(s): Iturriaga H, Bunout D, Hirsch S, Ugarte G. Source: The American Journal of Clinical Nutrition. 1988 February; 47(2): 235-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3341254
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Oxyphenisatin and liver damage. Author(s): Watson D. Source: The Medical Journal of Australia. 1972 August 26; 2(9): 510. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5083605
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Oxyphenisatin and liver damage. Author(s): Willing RL, Hecker R. Source: The Medical Journal of Australia. 1971 May 29; 1(22): 1179-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5557089
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Paracetamol overdose and liver damage. Author(s): Rose PG. Source: British Medical Journal. 1969 February 8; 1(640): 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5762848
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Paracetamol overdose in man: relationship between pattern of urinary metabolites and severity of liver damage. Author(s): Davis M, Simmons CJ, Harrison NG, Williams R. Source: The Quarterly Journal of Medicine. 1976 April; 45(178): 181-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=940917
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Paracetamol poisoning. Prevention of liver damage. Author(s): Prescott LF. Source: Med Chir Dig. 1979; 8(5): 391-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=534015
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Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Author(s): Cobden I, Record CO, Ward MK, Kerr DN. Source: British Medical Journal (Clinical Research Ed.). 1982 January 2; 284(6308): 21-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6797625
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Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Author(s): Gabriel R. Source: British Medical Journal (Clinical Research Ed.). 1982 February 13; 284(6314): 5056. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6800515
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Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Author(s): Prescott LF, Proudfoot AT, Cregeen RJ. Source: British Medical Journal (Clinical Research Ed.). 1982 February 6; 284(6313): 4212. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6800485
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Paracetamol-induced acute renal failure in the absence of severe liver damage. Author(s): Pillans P, Hall C. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1985 May 17; 67(20): 791-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3992409
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Pathogenesis of liver damage during parenteral nutrition: is lipofuscin a clue? Author(s): Berger HM, Den Ouden AL, Calame JJ. Source: Archives of Disease in Childhood. 1985 August; 60(8): 774-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3929700
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Pathophysiological aspects of dacarbazine-induced human liver damage. Author(s): Paschke R, Heine M. Source: Hepatogastroenterology. 1985 December; 32(6): 273-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4093126
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Phenytoin intoxication as the first symptom of fatal liver damage induced by sodium valproate. Author(s): Palm R, Silseth C, Alvan G. Source: British Journal of Clinical Pharmacology. 1984 May; 17(5): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6428444
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Plasma alpha-glutathione S-transferase (alpha-GST) as a marker of liver damage in hemodialysis patients. Author(s): Boran M, Cetin S. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998 May; 13(5): 1323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9623584
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Plasma alpha-glutathione S-transferase assessed as a marker of liver damage in patients with chronic hepatitis C. Author(s): Vaubourdolle M, Chazouilleres O, Briaud I, Legendre C, Serfaty L, Poupon R, Giboudeau J. Source: Clinical Chemistry. 1995 December; 41(12 Pt 1): 1716-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7497611
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Plasma carnitine levels in liver cirrhosis: relationship with nutritional status and liver damage. Author(s): Amodio P, Angeli P, Merkel C, Menon F, Gatta A. Source: J Clin Chem Clin Biochem. 1990 September; 28(9): 619-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1981222
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Plasma clearance of 99mTc-N/2,4-dimethyl-acetanilido/iminodiacetate complex as a measure of parenchymal liver damage. Author(s): Studniarek M, Durski K, Liniecki J. Source: Nuklearmedizin. 1983 June; 22(3): 140-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6622260
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Plasma glutathione S-transferase and F protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage. Author(s): Beckett GJ, Foster GR, Hussey AJ, Oliveira DB, Donovan JW, Prescott LF, Proudfoot AT. Source: Clinical Chemistry. 1989 November; 35(11): 2186-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2582614
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Plasma levels of apolipoproteins A-I, A-II and B in alcoholism. Relation to the degree of histological liver damage, and to liver function tests. Author(s): Malmendier CL, Mailier EL, Amerijckx JP, Fischer ML. Source: Hepatogastroenterology. 1983 December; 30(6): 236-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6427088
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Possible association of liver damage with the use of Chinese herbal medicine for skin disease. Author(s): Perharic L, Shaw D, Leon C, De Smet PA, Murray VS. Source: Vet Hum Toxicol. 1995 December; 37(6): 562-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8588298
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Possible liver damage by biosynthetic human insulin. Author(s): Shimizu H, Ohtani KI, Kudoh T, Tsuchiya T, Takahashi H, Sato N, Iriuchijima T, Mori M. Source: Diabetes, Obesity & Metabolism. 1999 May; 1(3): 179-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11220297
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Possible participation of endotoxin of gram-negative bacteria in pathogenesis of liver damage during viral hepatitis. Author(s): Sozinov AS. Source: Bulletin of Experimental Biology and Medicine. 2002 March; 133(3): 281-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360353
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Possible role of retinoids in hepatitis B virus-associated liver damage. Author(s): Mawson AR, Steele TA. Source: Experimental Biology and Medicine (Maywood, N.J.). 2001 September; 226(8): 734-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520938
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Prajmaliumbitartrate-associated liver damage. Report on seven further cases with follow-up for two to five years. Author(s): Borsch G, Schmidt G, Hopmann G, Surmann T, Sabin G, Ricken D. Source: Klin Wochenschr. 1984 October 15; 62(20): 998-1000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6503219
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Predictive value of HLA antigen for methotrexate-induced liver damage in patients with psoriasis. Author(s): Pestana A, Halprin KM, Taylor JR, Schiff ER, Esquenazi V, Comerford M, Gomez C. Source: Journal of the American Academy of Dermatology. 1985 January; 12(1 Pt 1): 269. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3980800
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PreS antigen expression and anti-preS response in hepatitis B virus infections: relationship to serum HBV-DNA, intrahepatic HBcAg, liver damage and specific Tcell response. Author(s): Petit MA, Capel F, Zoulim F, Dubanchet S, Chemin I, Penna A, Ferrari C, Trepo C. Source: Arch Virol Suppl. 1992; 4: 105-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1280500
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Preventive effect of malotilate on carbon tetrachloride-induced liver damage and collagen accumulation in the rat. Author(s): Ala-Kokko L, Stenback F, Ryhanen L. Source: The Biochemical Journal. 1987 September 1; 246(2): 503-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2825640
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Proceedings: Controlled trial of cysteamine and dimercaprol in the prevention of liver damage after paracetamol overdose. Author(s): Gazzard BG, Hughes RD, Chhibber AD, Bennett JR, Murray-Lyon IM, Dordoni B, Williams R. Source: Gut. 1975 October; 16(10): 839. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1107176
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Proceedings: Liver damage in patients taking methyldopa. Author(s): Toghill PJ, Smith PG, Benton P, Brown RC, Matthews HL. Source: Gut. 1974 April; 15(4): 342-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4834576
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Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage. Author(s): Morgan K, French SW, Morgan TR. Source: Hepatology (Baltimore, Md.). 2002 July; 36(1): 122-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12085356
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Prospective study and long-term follow-up of liver damage in renal transplant recipients. Author(s): Takahara S, Ihara H, Ichikawa Y, Nagano S, Fukunishi T, Sonoda T, Shinji Y. Source: Transplantation Proceedings. 1987 February; 19(1 Pt 3): 2221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3547920
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Protective and therapeutic effects of Curcuma xanthorrhiza on hepatotoxin-induced liver damage. Author(s): Lin SC, Lin CC, Lin YH, Supriyatna S, Teng CW. Source: The American Journal of Chinese Medicine. 1995; 23(3-4): 243-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8571920
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Pyrrolizidine (Senecio) poisoning in Arizona: severe liver damage due to herbal teas. Author(s): Stillman AE, Huxtable RJ, Fox D, Hart M, Bergeson P. Source: Ariz Med. 1977 August; 34(8): 545-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=901243
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Quantification of liver damage and prediction of 1-year survival after liver transplantation by a multifactorial “recovery score”. Author(s): Avolio AW, Agnes S, Magalini SC, Nanni G, Castagneto M. Source: Transplantation Proceedings. 1993 April; 25(2): 1868-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8470206
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Re: liver damage among shoe repairers. Author(s): Liss GM. Source: American Journal of Industrial Medicine. 2000 June; 37(6): 669. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10797512
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Relationship of blood trace elements to liver damage, nutritional status, and oxidative stress in chronic nonalcoholic liver disease. Author(s): Loguercio C, De Girolamo V, Federico A, Feng SL, Crafa E, Cataldi V, Gialanella G, Moro R, Del Vecchio Blanco C. Source: Biological Trace Element Research. 2001 September; 81(3): 245-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575681
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Relationship of color blindness to alcoholic liver damage. Author(s): Ugarte G, Cruz-Coke R, Rivera L, Altschiller H, Mardones J. Source: Pharmacology. 1970; 4(5): 297-308. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5312721
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Repeated halothane anaesthesia and possible liver damage. Author(s): Tammisto T, Tiitinen P, Elfving G, Hastbacka J. Source: Ann Chir Gynaecol Fenn. 1967; 56(1): 45-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6030221
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Reversal of liver damage due to long term methyltestosterone and safety of non-17 alpha-alkylated androgens. Author(s): Lowdell CP, Murray-Lyon IM. Source: British Medical Journal (Clinical Research Ed.). 1985 September 7; 291(6496): 637. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3928062
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Reversibility of extensive liver damage in galactosemia. Author(s): Applebaum MN, Thaler MM. Source: Gastroenterology. 1975 August; 69(2): 496-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1150052
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Reye syndrome: pathogenesis of encephalopathy in the initial stage not related to liver damage. Author(s): Yoshida I, Yoshino M, Yamashita F, Ono E, Katafuchi Y, Ikejiri N, Tanikawa K. Source: Kurume Med J. 1980; 27(4): 269-73. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7300243
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Role of fas ligand in uveal melanoma-induced liver damage. Author(s): Repp AC, Mayhew ES, Howard K, Alizadeh H, Niederkorn JY. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2001 October; 239(10): 752-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11760036
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Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral control. Author(s): Bertoletti A, Maini M, Williams R. Source: Antiviral Research. 2003 October; 60(2): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638399
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Role of H-ras gene in chronic liver damage in mice. By using transgenic mice carrying a human C-H-ras proto-oncogene without mutations. Author(s): Tsunematsu S, Saito H, Sato R, Morizane T, Ishii H. Source: Biochem Mol Biol Int. 1997 June; 42(2): 371-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9238536
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Role of liver function tests in detecting methotrexate-induced liver damage in sarcoidosis. Author(s): Baughman RP, Koehler A, Bejarano PA, Lower EE, Weber FL Jr. Source: Archives of Internal Medicine. 2003 March 10; 163(5): 615-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622609
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Score-aided decision making in patients with severe liver damage after hepatic transplantation. Author(s): Gubernatis G, Tusch G, Ringe B, Bunzendahl H, Pichlmayr R. Source: World Journal of Surgery. 1989 May-June; 13(3): 259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2662625
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Sensitivity of serum bile acid assay for detection of liver damage in viral hepatitis type B. Prospective study in five patients. Author(s): Hofmann AF, Korman MG, Krugman S. Source: Am J Dig Dis. 1974 October; 19(10): 908-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4421567
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Seroepidemiology of TT virus infection and relationship between genotype and liver damage. Author(s): Tanaka Y, Hayashi J, Ariyama I, Furusyo N, Etoh Y, Kashiwagi S. Source: Digestive Diseases and Sciences. 2000 November; 45(11): 2214-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11215742
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Serological evidence of hepatitis B virus and hepatitis delta virus infection in 164 patients with histological evidence of liver damage. Author(s): Greenfield C, Shah MV, Okoth F, Gatei D, Jowett T, Karayannis P, Wankya BM. Source: East Afr Med J. 1986 September; 63(9): 585-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3792250
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Serum activities of classes I and II alcohol dehydrogenases in toxic liver damage. Author(s): Chrostek L, Szmitkowski M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 March 23; 271(2): 163-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565331
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Serum ferritin in alcoholics and the relation to liver damage, iron state and erythropoietic activity. Author(s): Lundin L, Hallgren R, Birgegard G, Wide L. Source: Acta Med Scand. 1981; 209(4): 327-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7234511
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Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C. Author(s): Adinolfi LE, Utili R, Andreana A, Tripodi MF, Marracino M, Gambardella M, Giordano M, Ruggiero G. Source: Digestive Diseases and Sciences. 2001 August; 46(8): 1677-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11508667
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Serum HCV RNA titer does not predict the severity of liver damage in HCV carriers with normal aminotransferase levels. Author(s): Puoti C, Stati T, Magrini A. Source: Liver. 1999 April; 19(2): 104-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10220739
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Serum hyaluronate as a marker of hepatic derangement in acute liver damage. Author(s): Bramley PN, Rathbone BJ, Forbes MA, Cooper EH, Losowsky MS. Source: Journal of Hepatology. 1991 July; 13(1): 8-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1918880
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Serum hyaluronate in primary biliary cirrhosis--a biochemical marker for progressive liver damage. Author(s): Nyberg A, Engstrom-Laurent A, Loof L. Source: Hepatology (Baltimore, Md.). 1988 January-February; 8(1): 142-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3338702
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Serum hyaluronidase activity in chronic liver damage. Author(s): Nakamura N, Iwabori N, Koizumi T. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1970 January; 27(1): 47-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4312814
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Serum lactate dehydrogenase in detecting liver damage associated with preeclampsia. Author(s): Shukla PK, Sharma D, Mandal RK. Source: British Journal of Obstetrics and Gynaecology. 1978 January; 85(1): 40-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=623724
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Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage. Author(s): Ferre N, Camps J, Prats E, Vilella E, Paul A, Figuera L, Joven J. Source: Clinical Chemistry. 2002 February; 48(2): 261-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11805006
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Serum thyroid hormone levels in patients with liver damage: evidence of multiple abnormalities in presence of euthyroidism. Author(s): Mehta MN, Patel MC, Joseph LJ, Velumani A, Desai KB. Source: J Assoc Physicians India. 1988 November; 36(11): 637-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3150381
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Serum transaminase activity in leprosy in relation to liver damage. Author(s): Shivde AV, Junnarkar RV. Source: International Journal of Leprosy and Other Mycobacterial Diseases : Official Organ of the International Leprosy Association. 1967 July-September; 35(3): 366-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5630357
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Serum type III procollagen aminopeptide for assessing liver damage in methotrexatetreated psoriatic patients. Author(s): Boffa MJ, Smith A, Chalmers RJ, Mitchell DM, Rowan B, Warnes TW, Shomaf M, Haboubi NY. Source: The British Journal of Dermatology. 1996 October; 135(4): 538-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8915142
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Serum type III procollagen peptide as a non-invasive marker of liver damage during infancy and childhood in extrahepatic biliary atresia, idiopathic hepatitis of infancy and alpha 1 antitrypsin deficiency. Author(s): Trivedi P, Cheeseman P, Portmann B, Mowat AP. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1986 December 15; 161(2): 137-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3492313
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Severe liver damage caused by therapeutic doses of acetaminophen. Author(s): Floren CH, Thesleff P, Nilsson A. Source: Acta Med Scand. 1987; 222(3): 285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3425381
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Severe liver damage caused by treatment of psoriasis with methotrexate. Author(s): Pai SH, Werthamer S, Zak FG. Source: N Y State J Med. 1973 November 1; 73(21): 2585-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4518596
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Short and long-term effects of bacterial translocation due to obstructive jaundice on liver damage. Author(s): Sakrak O, Akpinar M, Bedirli A, Akyurek N, Aritas Y. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1542-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571782
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Significance of serum type IV collagen level of hepatectomized patients with chronic liver damage. Author(s): Shimahara Y, Yamamoto N, Uyama N, Okuyama H, Momoi H, Kamikawa T, Terajima H, Iimuro Y, Yamamoto Y, Ikai I, Kushihata F, Kiyochi H, Kobayashi N, Yamaoka Y. Source: World Journal of Surgery. 2002 April; 26(4): 451-6. Epub 2002 February 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910479
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Sleep disorders. Liver damage warning with insomnia remedy. Author(s): Shepherd C. Source: Bmj (Clinical Research Ed.). 1993 May 29; 306(6890): 1477. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8357398
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Small hepatocellular carcinoma in patients with chronic liver damage: prospective comparison of detection with dynamic MR imaging and helical CT of the whole liver. Author(s): Yamashita Y, Mitsuzaki K, Yi T, Ogata I, Nishiharu T, Urata J, Takahashi M. Source: Radiology. 1996 July; 200(1): 79-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8657948
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Spectrum of liver damage and correlation with clinical and laboratory parameters in HCV infected hemodialysis patients. Author(s): Sezer S, Ozdemir BH, Arat Z, Turan M, Ozdemir NF, Haberal M. Source: Renal Failure. 2001 November; 23(6): 807-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777320
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Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Author(s): Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Source: Hepatology (Baltimore, Md.). 2001 June; 33(6): 1358-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391523
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Studies on the intestinal absorption of thiamine, riboflavin and calcium in liver damage. Author(s): Miyao M, Matsuda H, Usui T, Tanaka H, Kochi T. Source: Tokushima J Exp Med. 1967 June; 14(1): 1-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6080935
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Subtypes of Australia antigen among patients and healthy carriers in Copenhagen. A relation between the subtypes and the degree of liver damage in acute viral hepatitis. Author(s): Nielsen JO, Le Bouvier GL. Source: The New England Journal of Medicine. 1973 June 14; 288(24): 1257-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4703314
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Suprahepatic vein oxygen tension in alcoholics with severe and mild liver damage. Author(s): Bunout D, Moya P, de la Maza MP, Petermann M, Iturriaga H, Hirsch S. Source: Digestive Diseases and Sciences. 1995 June; 40(6): 1243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7781440
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Tamoxifen and liver damage. Author(s): Blackburn AM, Amiel SA, Millis RR, Rubens RD. Source: British Medical Journal (Clinical Research Ed.). 1984 August 4; 289(6440): 288. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6430441
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The antioxidant status of patients with either alcohol-induced liver damage or myopathy. Author(s): Ward RJ, Peters TJ. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 1992 July; 27(4): 359-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1418110
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The common pattern of cytokeratin alteration in alcoholic and cholestatic liver disease is different from that of hepatitic liver damage. A study with the panepithelial monoclonal antibody lu-5. Author(s): Mullhaupt B, Gudat F, Epper R, Bianchi L. Source: Journal of Hepatology. 1993 August; 19(1): 23-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7507954
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The effect of diet on the severity of liver damage in acute alcoholic hepatitis. Author(s): Fung WP, Tan KK, Tye CY. Source: Singapore Med J. 1972 October; 13(5): 224-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4651726
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The effect of Naftidrofuryl on ethanol-induced liver damage in chronic alcoholic patients. Author(s): Majumdar SK, Shaw GK, O'Gorman P, Thomson AD. Source: Drug and Alcohol Dependence. 1982 October-November; 10(2-3): 135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6131800
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The extrapolation of liver function data from the animal to the human in the treatment of the acute stage of liver damage with the hepatotropic factor. Author(s): Timar M. Source: Farmaco [prat]. 1976 September; 31(9): 473-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1010021
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The incidence of oxyphenisatin-induced liver damage in chronic non-alcoholic liver disease. A controlled investigation. Author(s): Dietrichson O, Juhl E, Nielsen JO, Oxlund JJ, Christoffersen P. Source: Scandinavian Journal of Gastroenterology. 1974; 9(5): 473-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4605276
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The influence of liver damage in man on the distribution and disposal rates of thyroxine and triiodothyronine. Author(s): McConnon J, Row VV, Volpe R. Source: The Journal of Clinical Endocrinology and Metabolism. 1972 January; 34(1): 14451. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4621462
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The relation between liver iron concentration and liver damage in transfusional iron overload in thalassaemia and the effect of chelation therapy. Author(s): Risdon RA, Flynn DM, Barry M. Source: Gut. 1973 May; 14(5): 421. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4716515
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The relationship between brain and liver damage in chronic alcoholic patients. Author(s): Acker W, Aps EJ, Majumdar SK, Shaw GK, Thomson AD. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1982 November; 45(11): 984-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7175542
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The role of CYP enzymes in cocaine-induced liver damage. Author(s): Pasanen M, Pellinen P, Stenback F, Juvonen RO, Raunio H, Pelkonen O. Source: Archives of Toxicology. 1995; 69(5): 287-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7654131
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The role of lipid peroxidation in liver damage. Author(s): Poli G, Albano E, Dianzani MU. Source: Chemistry and Physics of Lipids. 1987 November-December; 45(2-4): 117-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3319224
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The use of antipyrine clearance to measure liver damage in psoriatic patients receiving methotrexate. Author(s): Paramsothy J, Strange R, Sharif H, Collins M, Shaw P, Lawrence CM. Source: The British Journal of Dermatology. 1988 December; 119(6): 761-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3203069
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The value of angiographic methods in diagnostic assessment of liver damage in portal hypertension. Author(s): Galmarini D, Fassati LR, Riquier G, Trivellini G, Zanoll PG. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1969 June 14; 43(24): 743-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5794385
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Tissue acetylsalicylic acid esterase activity in rats with acute and chronic liver damage from carbon-tetrachloride and ethanol. Author(s): Juggi JS. Source: Enzyme. 1975; 20(3): 183-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1168570
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Toxic liver damage due to ethionamide. Author(s): Kuntz E, Liehr H, Pfingst W. Source: Ger Med Mon. 1968 December; 13(12): 599-602. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5735341
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Trimethadione tolerance test for one-point estimation of the severity of liver damage in cirrhotic patients. Author(s): Tanaka E, Ishikawa A, Fukao K, Tsuji K, Osada A, Yamamoto Y, Adachi S, Takase Y, Abei M, Iwasaki Y. Source: Int J Clin Pharmacol Ther Toxicol. 1991 August; 29(8): 333-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1743808
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TT virus (TTV) is unlikely to cause chronic liver damage. Author(s): Imawari M. Source: Journal of Gastroenterology. 1999 April; 34(2): 292-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10213136
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Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis. Author(s): Neuman M, Angulo P, Malkiewicz I, Jorgensen R, Shear N, Dickson ER, Haber J, Katz G, Lindor K. Source: Journal of Gastroenterology and Hepatology. 2002 February; 17(2): 196-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966951
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Type 2 diabetes therapy and liver damage: the debate continues. Author(s): Zangeneh F, Basu A. Source: Postgraduate Medicine. 2002 September; 112(3): 23; Author Reply 23-4, 82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360654
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Ultrasound and radionuclide scans--poor indicators of liver damage in patients treated with methotrexate. Author(s): Mitchell D, Johnson RJ, Testa HJ, Haboubi NY, Chalmers RJ. Source: Clinical and Experimental Dermatology. 1987 July; 12(4): 243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3322613
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Unusual liver damage ensuing after warfarin administration in a pregnant woman with caval thrombosis. Author(s): Amitrano L, Guardascione MA, Balzano A, Brancaccio V, Iannaccone L, Ames PR. Source: Dig Liver Dis. 2003 January; 35(1): 61-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725611
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Urinary metabolic profile of isoniazid in patients who develop isoniazid-related liver damage. Author(s): Timbrell JA, Wright JM. Source: Hum Toxicol. 1984 December; 3(6): 485-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6526396
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Urinary porphyrin pattern in liver damage. Author(s): de Rover CM, Rukmini C, Tulpule PG. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1984 March; 22(3): 241-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6538543
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Use of the triolein breath test in alcoholics with liver damage. Author(s): Korsten MA, Klapholz MB, Leaf MA, Lieber CS. Source: The Journal of Laboratory and Clinical Medicine. 1987 January; 109(1): 62-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3794517
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Valproic acid and liver damage. Author(s): Gram L, Bentsen K. Source: Acta Paediatr Scand. 1985 September; 74(5): 796-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3931410
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Variations in HDL and VLDL levels chronic alcoholics. Influence of the degree of liver damage and of withdrawal of alcohol. Author(s): Tateossian S, Peynet JG, Legrand AG, Collet B, Rossignol JA, Delattre JJ, Rousselet FJ. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1985 June 14; 148(3): 211-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4042355
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Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection. Author(s): Chan HL, Tsang SW, Liew CT, Tse CH, Wong ML, Ching JY, Leung NW, Tam JS, Sung JJ. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 406-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11866280
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Virus- and immune-mediated liver damage in hepatitis. Author(s): Eddleston AL. Source: Intervirology. 1993; 35(1-4): 122-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8407239
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Vitamin E and liver damage in MZ heterozygous infants with alpha 1-antitrypsin deficiency. Author(s): Pittschieler K. Source: Acta Paediatrica (Oslo, Norway : 1992). 1993 March; 82(3): 228-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8495073
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What determines susceptibility to liver damage from alcohol?: discussion paper. Author(s): Saunders JB, Wodak AD, Williams R. Source: Journal of the Royal Society of Medicine. 1984 March; 77(3): 204-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6366230
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CHAPTER 2. NUTRITION AND LIVER DAMAGE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and liver damage.
Finding Nutrition Studies on Liver Damage 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 damage” (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 damage: •
By the way, doctor. My neighbor takes something called milk thistle. He likes to drink alcohol and believes the herb will protect him against any kind of liver damage. Is he right? Source: Lee, T H Harv-Health-Lett. 2001 July; 26(9): 8 1052-1577
The following information is typical of that found when using the “Full IBIDS Database” to search for “liver damage” (or a synonym): •
An effect of bromobenzene treatment on the liver damage of rats previously fed low or high protein diet. Author(s): Kyungsan University, Kyungsan (Korea Republic). Department of Health ScienceKeimyung University, Taegu (Korea Republic). Department of Public Health Source: Shin, J.K. Chae, S.N. Yoon, C.G. Journal-of-The-Korean-Society-of-Food-andNutrition (Korea Republic). (December 1994). volume 23(6) page 894-898. 0253-3154
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Effect of dietary tungstate on the liver damage in CCl4-treated rats. Author(s): Keimyung University, Taegu (Korea Republic). Department of Public HealthKeimyung Junior College, Taegu (Korea Republic). Department of Food and Nutrition Source: Yoon, C.G. Park, H.S. Lee, S.I. Journal-of-The-Korean-Society-of-Food-andNutrition (Korea Republic). (December 1993). volume 22(6) page 678-684. 0253-3154
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Effects of heated oil and vitamin E on lipid peroxidative liver damage in rat. Author(s): Hyosung Women' s University, Kyungsan (Korea Republic). Department of Food Science and Nutrition Source: Rhee, S.J. Korean-Society-of-Food-and-Nutrition (Korea Republic). (April 1991). volume 20(2) page111-120.
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Effects of S-adenosyl-L-methionine on liver damage in experimental obstructive jaundice. Author(s): Department of Health Public, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Source: Tsai, S M Lee, K T Tsai, L Y Kaohsiung-J-Med-Sci. 2001 September; 17(9): 455-60 1607-551X
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Esculetin prevents liver damage induced by paracetamol and CCL4. Author(s): Department of Physiology and Pharmacology, Aga Khan University Medical College, Karachi, Pakistan. Source: Gilani, A H Janbaz, K H Shah, B H Pharmacol-Res. 1998 Jan; 37(1): 31-5 10436618
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Hepatoprotective Activity of Moringa oleifera on Antitubercular Drug-Induced Liver Damage in Rats. Author(s): Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu - 608 002, India. Source: Pari, L KuMarch, N A J-Med-Food. 2002 Fall; 5(3): 171-7 1096-620X
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Hepatoprotective effect of coumestans isolated from the leaves of Wedelia calendulacea Less. in paracetamol induced liver damage. Author(s): Entomology Research Institute, Loyola College, Chennai, India. Source: Emmanuel, S Amalraj, T Ignacimuthu, S Indian-J-Exp-Biol. 2001 December; 39(12): 1305-7 0019-5189
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Herb used to treat anxiety now linked to liver damage. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. March 2002. volume 20 (1) page 6.
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Kava kava may cause irreversible liver damage. Source: Anonymous S-Afr-Med-J. 2002 December; 92(12): 961 0038-2469
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Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes. Author(s): Dpto Farmacologia, Facultad de Farmacia Universidad Complutense de Madrid, Spain. Source: Martin Aragon, S de las Heras, B Sanchez Reus, M I Benedi, J Exp-ToxicolPathol. 2001 June; 53(2-3): 199-206 0940-2993
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Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. Author(s): Section of Gastroenterology and Nutrition, Division of Digestive Diseases, Department of Internal Medicine, Rush Presbyterian St. Lukes Medical Center, Chicago, Illinois 60612, USA.
[email protected] Source: Keshavarzian, A Choudhary, S Holmes, E W Yong, S Banan, A Jakate, S Fields, J Z J-Pharmacol-Exp-Ther. 2001 November; 299(2): 442-8 0022-3565
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Protection by pantothenol and beta-carotene against liver damage produced by lowdose gamma radiation. Author(s): Institute of Biochemistry, National Academy of Sciences of Belarus, Grodno, Poland. Source: Slyshenkov, V S Omelyanchik, S N Moiseenok, A G Petushok, N E Wojtczak, L Acta-Biochim-Pol. 1999; 46(2): 239-48 0001-527X
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Protective effect of Cochlospermum tinctorium A. Rich extract versus aflatoxin B1induced liver damage in rats. Source: Dalvi, R.R. Sere, A. Int-J-Crude-Drug-Res. Lisse : Swets & Zeitlinger. June 1988. volume 26 (2) page 117-120. 0167-7314
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Protective effects of vitamin E on carbon tetrachloride-induced liver damage in rats. Author(s): Department of Physiology, Veterinary Faculty of Firat University 23119 Elazig, Turkey. Source: Naziroglu, M Cay, M Ustundag, B Aksakal, M Yekeler, H Cell-Biochem-Funct. 1999 December; 17(4): 253-9 0263-6484
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
The following is a specific Web list relating to liver damage; 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 Niacin Source: Integrative Medicine Communications; www.drkoop.com Niacin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,892,00.html Provitamin A Alternative names: Beta-Carotene Source: Integrative Medicine Communications; www.drkoop.com
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Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com •
Minerals Creatine Source: Integrative Medicine Communications; www.drkoop.com Phosphocreatine Source: Integrative Medicine Communications; www.drkoop.com
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Food and Diet Betaine (Trimethylglycine) Source: Healthnotes, Inc.; www.healthnotes.com Burdock Alternative names: Arctium lappa Source: Healthnotes, Inc.; www.healthnotes.com
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3.
ALTERNATIVE
MEDICINE
AND
LIVER
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to liver damage. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “liver damage” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Kava Linked to Liver Damage Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2002. 1 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL:
[email protected]. PRICE: Free. Publication Number: D148. Summary: This consumer advisory reports that the Food and Drug Administration (FDA) is advising consumers of the potential risk of severe liver injury from the use of dietary supplements containing kava. It cites recent reports that have linked kava to liver toxicity, and provides advice to consumers based on these reports. The advisory also reports that the National Center for Complementary and Alternative Medicine is
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supporting two research studies on kava, and these studies are on hold pending further guidance from the FDA.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to liver damage and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “liver damage” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to liver damage: •
(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. Author(s): Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1999 February; 13(2): 411-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973329
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Antioxidant and hepatoprotective effects of punicalagin and punicalin on acetaminophen-induced liver damage in rats. Author(s): Lin CC, Hsu YF, Lin TC, Hsu HY. Source: Phytotherapy Research : Ptr. 2001 May; 15(3): 206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11351354
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Astilbin selectively induces dysfunction of liver-infiltrating cells--novel protection from liver damage. Author(s): Xu Q, Wu F, Cao J, Chen T, Jiang J, Saiki I, Koda A. Source: European Journal of Pharmacology. 1999 July 14; 377(1): 93-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448932
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By the way, doctor. My neighbor takes something called milk thistle. He likes to drink alcohol and believes the herb will protect him against any kind of liver damage. Is he right? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2001 July; 26(9): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511452
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Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats. Author(s): Bhanwra S, Singh J, Khosla P.
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Source: Indian J Physiol Pharmacol. 2000 January; 44(1): 64-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10919097 •
Effect of high fiber vegetable-fruit diet on the activity of liver damage and serum iron level in porphyria cutanea tarda (PCT). Author(s): Dabrowska E, Jablonska-Kaszewska I, Falkiewicz B. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 May; 7 Suppl 1: 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211737
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Effects of dietary polyunsaturated fatty acids and nucleotides on tissue fatty acid profiles of rats with carbon tetrachloride-induced liver damage. Author(s): Fontana L, Moreira E, Torres MI, Periago JL, Sanchez de Medina F, Gil A. Source: Clinical Nutrition (Edinburgh, Lothian). 1999 April; 18(2): 93-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10459066
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Effects of quercetin on liver damage in rats with carbon tetrachloride-induced cirrhosis. Author(s): Pavanato A, Tunon MJ, Sanchez-Campos S, Marroni CA, Llesuy S, GonzalezGallego J, Marroni N. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 824-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741479
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Effects of silymarin and vitamins E and C on liver damage induced by prolonged biliary obstruction in the rat. Author(s): Muriel P, Moreno MG. Source: Basic Clin Pharmacol Toxicol. 2004 February; 94(2): 99-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14748853
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Evaluation of the protective potential of Ambrosia maritima extract on acetaminophen-induced liver damage. Author(s): Ahmed MB, Khater MR. Source: Journal of Ethnopharmacology. 2001 May; 75(2-3): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11297846
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Gut-liver axis: a new point of attack to treat chronic liver damage? Author(s): Loguercio C, De Simone T, Federico A, Terracciano F, Tuccillo C, Di Chicco M, Carteni M. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2144-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190198
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Hepatoprotective activity of Ficus racemosa leaf extract on liver damage caused by carbon tetrachloride in rats. Author(s): Mandal SC, Maity TK, Das J, Pal M, Saha BP. Source: Phytotherapy Research : Ptr. 1999 August; 13(5): 430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10441787
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Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats. Author(s): Pari L, Kumar NA. Source: Journal of Medicinal Food. 2002 Fall; 5(3): 171-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495589
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Hepatoprotective activity of Trichilia roka on carbon tetrachloride-induced liver damage in rats. Author(s): Germano MP, D'Angelo V, Sanogo R, Morabito A, Pergolizzi S, De Pasquale R. Source: The Journal of Pharmacy and Pharmacology. 2001 November; 53(11): 1569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11732761
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Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice. Author(s): Trivedi NP, Rawal UM. Source: Indian J Exp Biol. 2001 January; 39(1): 41-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11349524
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Hepatoprotective effect of Vitex negundo against carbon tetrachloride-induced liver damage. Author(s): Avadhoot Y, Rana AC. Source: Arch Pharm Res. 1991 March; 14(1): 96-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319130
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Hepatoprotective effects of Andrographis paniculata against carbon tetrachlorideinduced liver damage. Author(s): Rana AC, Avadhoot Y. Source: Arch Pharm Res. 1991 March; 14(1): 93-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319129
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Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage. Author(s): Lin SC, Chung TC, Lin CC, Ueng TH, Lin YH, Lin SY, Wang LY. Source: The American Journal of Chinese Medicine. 2000; 28(2): 163-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999435
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Hepatoprotective effects of Liv-52 on ethanol induced liver damage in rats. Author(s): Sandhir R, Gill KD. Source: Indian J Exp Biol. 1999 August; 37(8): 762-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10709323
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Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice. Author(s): Lee KJ, You HJ, Park SJ, Kim YS, Chung YC, Jeong TC, Jeong HG. Source: Cancer Letters. 2001 December 10; 174(1): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11675154
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Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats. Author(s): Casey CA, McVicker BL, Donohue TM Jr, McFarland MA, Wiegert RL, Nanji AA. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2004 January; 96(1): 76-80. Epub 2003 August 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949020
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Nardostachys jatamansi protects against liver damage induced by thioacetamide in rats. Author(s): Ali S, Ansari KA, Jafry MA, Kabeer H, Diwakar G. Source: Journal of Ethnopharmacology. 2000 August; 71(3): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10940571
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Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes. Author(s): Martin-Aragon S, de las Heras B, Sanchez-Reus MI, Benedi J. Source: Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie. 2001 June; 53(2-3): 199-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484840
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Protective effect of Nigella sativa seeds against carbon tetrachloride-induced liver damage. Author(s): Al-Ghamdi MS. Source: The American Journal of Chinese Medicine. 2003; 31(5): 721-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696675
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Protective effect of turmeric (Curcuma longa L.) extract on carbon tetrachlorideinduced liver damage in rats. Author(s): Deshpande UR, Gadre SG, Raste AS, Pillai D, Bhide SV, Samuel AM.
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Source: Indian J Exp Biol. 1998 June; 36(6): 573-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9731471 •
Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophenand CCl4-induced liver damage in rats. Author(s): Ryu BK, Ahn BO, Oh TY, Kim SH, Kim WB, Lee EB. Source: Arch Pharm Res. 1998 October; 21(5): 508-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9875486
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The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice. Author(s): Mahmoud MR, El-Abhar HS, Saleh S. Source: Journal of Ethnopharmacology. 2002 January; 79(1): 1-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744288
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The effectiveness of Tsu-San-Li (St-36) and Tai-Chung (Li-3) acupoints for treatment of acute liver damage in rats. Author(s): Liu HJ, Hsu SF, Hsieh CC, Ho TY, Hsieh CL, Tsai CC, Lin JG. Source: The American Journal of Chinese Medicine. 2001; 29(2): 221-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527065
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The evaluation of the therapeutic effect of tao-shang-tsao on alphanaphthylisothiocyanate and carbon tetrachloride-induced acute liver damage in rats. Author(s): Lu KL, Chang YS, Ho LK, Lin CC, Tsai CC. Source: The American Journal of Chinese Medicine. 2000; 28(3-4): 361-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11154049
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The failure of selenium supplementation to prevent copper-induced liver damage in Fischer 344 rats. Author(s): Aburto EM, Cribb A, Fuentealba IC, Ikede BO, Kibenge FS, Markham F. Source: Canadian Journal of Veterinary Research = Revue Canadienne De Recherche Veterinaire. 2001 April; 65(2): 104-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346254
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The flavonoid naringenin inhibits dimethylnitrosamine-induced liver damage in rats. Author(s): Lee MH, Yoon S, Moon JO. Source: Biological & Pharmaceutical Bulletin. 2004 January; 27(1): 72-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14709902
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The flavonoid quercetin ameliorates liver damage in rats with biliary obstruction. Author(s): Peres W, Tunon MJ, Collado PS, Herrmann S, Marroni N, Gonzalez-Gallego J.
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Source: Journal of Hepatology. 2000 November; 33(5): 742-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097482 •
The flavonoid quercetin inhibits dimethylnitrosamine-induced liver damage in rats. Author(s): Lee ES, Lee HE, Shin JY, Yoon S, Moon JO. Source: The Journal of Pharmacy and Pharmacology. 2003 August; 55(8): 1169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956909
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Yang-Gan-Wan protects mice against experimental liver damage. Author(s): Yang M, Chen K, Shih JC. Source: The American Journal of Chinese Medicine. 2000; 28(2): 155-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10999434
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to liver damage; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com
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Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Gallbladder Disease Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com •
Herbs and Supplements 5-Hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com Acetaminophen Source: Healthnotes, Inc.; www.healthnotes.com Acetaminophen Alternative names: Acephen, Aceta, Amaphen, Anoquan, Apacet, Arthritis Foundation Aspirin Free, Arthritis Foundation Nighttime, Aspirin Free Anacin, Aspirin Free Excedrin, Bayer Select, Dapacin, Dynafed, Endolor, Esgic, Excedrin P.M., Fem-Etts, Femcet, Feverall, Fioricet, Fiorpap, Genapap, Genebs, Halenol,
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Isocet, Liquiprin, Mapap, Maranox, Meda, Medigesic, Midol, Multi-Symptom Pamprin, Neopap, Nighttime Pamprin, Oraphen-PD, Panadol, Phrenilin, Repan, Ridenol, Sedapap, Silapap, Sominex Pain Relief, Tapanol, Tempra, Tylenol, Uni-Ace, Unisom with Pain Relief Source: Prima Communications, Inc.www.personalhealthzone.com American Scullcap Alternative names: Scutellaria lateriflora Source: Healthnotes, Inc.; www.healthnotes.com Angkak Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Arctium Alternative names: Burdock, Gobo; Arctium lappa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arnica Alternative names: Arnica montana L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ava Source: Integrative Medicine Communications; www.drkoop.com B-carotene Alternative names: Beta-Carotene Source: Integrative Medicine Communications; www.drkoop.com Beni-koji Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Beta-carotene Alternative names: Betacarotenum Source: Integrative Medicine Communications; www.drkoop.com Betacarotenum Alternative names: Beta-Carotene Source: Integrative Medicine Communications; www.drkoop.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Boneset Alternative names: Eupatorium perfoliatum Source: Healthnotes, Inc.; www.healthnotes.com Clofibrate Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org General Anesthetics Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Haloperidol Source: Healthnotes, Inc.; www.healthnotes.com Hong Qu Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Hung-chu Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Isoniazid Source: Healthnotes, Inc.; www.healthnotes.com Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Lipotropic Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,861,00.html Milk Thistle Alternative names: Silybum marianum, St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Milk Thistle Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Milk Thistle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html Monascus Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Nitrous Oxide Source: Healthnotes, Inc.; www.healthnotes.com PABA Source: Healthnotes, Inc.; www.healthnotes.com Peppermint Alternative names: Mentha piperita Source: Healthnotes, Inc.; www.healthnotes.com Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Plantago Major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Red Koji Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Leaven Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Rice Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com
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Red Yeast Rice Alternative names: Angkak Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10054,00.html S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe Source: Integrative Medicine Communications; www.drkoop.com Sassafras Alternative names: Sassafras albidum (Nuttall) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Marianum Source: Integrative Medicine Communications; www.drkoop.com Skullcap Source: Prima Communications, Inc.www.personalhealthzone.com St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Swertia Alternative names: Swertia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Symphytum Alternative names: Comfrey; Symphytum officinale L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tacrine Source: Healthnotes, Inc.; www.healthnotes.com Tanacetum V Alternative names: Tansy; Tanacetum vulgare (L.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Trans-beta-carotene Alternative names: Beta-Carotene Source: Integrative Medicine Communications; www.drkoop.com Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Uva Ursi Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10063,00.html Valeriana Alternative names: Valerian; Valeriana officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zhitai Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Zue Zhi Kang Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. CLINICAL TRIALS AND LIVER DAMAGE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning liver damage.
Recent Trials on Liver Damage The following is a list of recent trials dedicated to liver damage.8 Further information on a trial is available at the Web site indicated. •
Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation Condition(s): veno-occlusive disease Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Giving defibrotide may be an effective treatment for liver damage that may result following peripheral stem cell transplantation. PURPOSE: Randomizedphase II trial to study the effectiveness of defibrotide in treating patients who have severe liver disease after undergoing peripheral stem cell transplantation. Phase(s): Phase II; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003966
8
These are listed at www.ClinicalTrials.gov.
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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 damage” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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•
For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 5. PATENTS ON LIVER DAMAGE 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 damage” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on liver damage, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Liver Damage By performing a patent search focusing on liver damage, 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 damage: •
Antioxidant composition diketogulonic acid
in
vivo
comprising
enol
form.delta.-lactone
of
Inventor(s): Kimoto; Eiji (Fukuoka, JP) Assignee(s): Nissan Chemical Industries, Ltd. (tokyo, Jp) Patent Number: 5,162,366 Date filed: January 24, 1991 Abstract: Enol form.delta.-lactone of diketogulonic acid (2,3,6-trihydroxy-4-oxo-2-hexen5-olide; R-345), which is the enediol type oxidation product of ascorbic acid, and/or its sodium salt, potassium salt or calcium salt has activities of markedly reducing the toxicity of Adriamycin, reducing radiation injury, reducing liver damage induced by an organic halogen compound, and further accelerating recovery from a high blood sugar level in Alloxan-induced diabetes, using vitanim E in combination. Excerpt(s): The present invention relates to an in vivo antioxidant composition comprising enol form.delta.-lactone of diketogulonic acid (2,3,6-trihydroxy-4-oxo-2hexen-5-olide) and/or its sodium salt, potassium salt or calcium salt and more particularly, to a composition for reducing the toxicity of Adriamycin using in combination with vitamin E which is a fat-soluble antioxidant, a composition for reducing radiation injury using in combination with vitamin E, a composition for reducing disturbance due to lipid peroxidation in liver using in combination with vitamin E, a composition for reducing a peroxidized state in vivo, for example, a peroxidized state in vivo in Alloxan-induced diabetes, and a composition for reducing a peroxidized state in vivo in a broad sense. The present invention also relates to a method for reducing or improving a peroxidized state in vivo by administering the aforesaid drug composition to mammal or human. Anti-tumor agents such as Adriamycin generate activated oxygen to cause peroxidation in myocardiac tissue, etc. Due to these severe side effects, it is difficult to sufficiently enhance their therapeutic coefficient. Web site: http://www.delphion.com/details?pn=US05162366__ •
Loss of sialic acid from apolipoprotein j as an indicator of alcohol intake and/or alcohol related liver damage Inventor(s): Ghosh; Pradeep (Gaithersburg, MD), Hale; Eric Anthony (Baltimore, MD), Lakshman; Raj (Bethesda, MD) Assignee(s): Bioprobes, Inc. (gathersburg, Md) Patent Number: 6,498,038 Date filed: January 13, 2000 Abstract: Disclosed is a method for determining alcohol intake or alcohol induced liver damage in a subject by quantifying the content of sialic acid in apolipoprotein J (Apo J). In particular the present invention involves the steps of (a) providing a sample containing Apo J from a subject; (b) purifying the Apo J from the sample; (c) determining sialylation index, i.e., moles of sialic acid peer mole of Apo J in the sample; and (d) evaluating whether the sialylation index is an indication of alcohol intake or
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alcohol related liver damage recovery from alcohol addiction or alcohol relapse in the subject. Excerpt(s): The present invention relates to a method for detecting pathological and metabolic changes related to alcohol intake in an individual, and more particularly to a method for detecting alcohol intake and alcohol related liver damage by measuring the sialylation index of apolipoprotein J. There are about 10 million alcoholics in the United States. Alcoholic liver disease is a major cause of morbidity and mortality in the United States and in many other countries in the world. Ethanol is toxic to the liver. Thus, the persistent, excessive intake of ethanol can lead to a number of complications in the human body, including damage to liver cells and eventually, to cirrhosis of the liver. Profound changes in the concentration and composition of plasma lipids and lipoproteins occur at each stage of excessive alcohol intake and/or alcohol-induced liver injury. Ghosh, P. et al., "Long-Term Ethanol Exposure Impairs Glycosylation of Both N-and O-- Glycosylated Proteins in Rat Liver," Metabolism 44: 890-898 (1995). One of the main sites of ethanol attack is the glycosylation machinery of the liver. This deleterious action of ethanol manifests itself by altering specific activities of the sialylation and desialylation enzymes of the liver which results in either defective sialylation of proteins or increased hydrolysis of molecules that eventually result in the depletion of sialic acid residues from sialylomolecules. See Ghosh, P. et al., "Effects of Chronic Ethanol on Enzymes Regulating Sialylation and Desialylation of Transferrin in Rats," Alcoh. Clin. Exp. Res. 17: 576-579 (1993). Hepatocellular degeneration results in a variety of clinical symptoms ranging from a relatively asymptomatic enlargement of the liver to massive fatty infiltration. As the alcohol abuse continues, these degenerative processes manifest themselves into liver dysfunction, chronic inflammation, and structural distortion of cells leading to proliferation of fibrous tissue, and ultimately to cirrhosis and necrosis of the liver. Total hepatic failure and death may occur as a result of prolonged alcohol abuse in humans. Web site: http://www.delphion.com/details?pn=US06498038__ •
Method for preventing or arresting liver damage in humans Inventor(s): Oren; Ran (2600 Netherland Ave., Riverdale, NY 10463) Assignee(s): None Reported Patent Number: 6,143,752 Date filed: July 31, 1998 Abstract: The invention provides methods for treating liver disease by inducing a hypothyroid state using (i) drugs, e.g., PTU, methimazole, lithium or carbimazole; (ii) surgery; or, (iii) radiation, e.g.,.sup.127 I or.sup.131 I. The liver diseases that can be treated using the methods of the invention include: infectious hepatitis, such as (i) viral hepatitis resulting from infection with hepatitis A, D, C, D, E, or G; or (ii) parasitic hepatitis resulting from infection with Schistosoma mansoni, Schistosoma hematobium or Schistosoma japonicum; or (iii) autoimmune disease, e.g., (a) autoimmune hepatitis or (b) primary biliary cirrhosis. Excerpt(s): This invention is directed to methods for preventing, attenuating, retarding or arresting liver damage caused by infection or autoimmune-mediated diseases. The liver is the target of attack for a wide range of diseases. These diseases include infectious, autoimmune, as well as non-infectious processes such as chemicals. Examples of infectious diseases include: (i) viral hepatitis, e.g., hepatitis A, B, C, D, E,
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and G and (ii) parasitic hepatitis, e.g., Schistosoma mansoni, Schistosoma hematobium, and Schistosoma japonicum. (Harrison's Principles of Internal Medicine, Fauci et al. eds., 1998, pgs 1660-1725). Examples of noninfectious diseases affecting the liver, include autoimmune diseases, such as, (i) autoimmune hepatitis and (ii) primary biliary cirrhosis. (Harrison's Principles of Internal Medicine, Fauci et al. eds., 1998, pgs 17011709). Regardless of whether the attack on the liver is infectious, autoimmune or noninfectious, the liver responds to injury by pouring inflammatory cells into the site of attack. The types of inflammatory cells entering the site of attack consist primarily of macrophages and neutrophils. After entry into the site of injury, the cells release various inflammatory cytokines, such as tumor necrosis factor (TNF). These cytokines mediate the local inflammatory response by inducing local changes, for example, proliferation of fibroblasts or vasodilation. If left untreated, repeated, chronic damage to the liver from infection, autoimmune disease or any other noninfectious processes causes scarring or fibrosis. This is a direct consequence of local proliferation of fibroblasts. (Kaplowitz, Biliary Diseases, pg. 139, Williams & Wilkins, 1992). In the case of the liver, the endstage of fibrosis is cirrhosis. Pathologically, cirrhosis is defined as extensive fibrosis in the liver in association with the formation of regenerative nodules. Cirrhosis is the final common pathway for many, if not all, types of chronic liver damage and is typically progressive. (Kaplowitz, Biliary Diseases, pg. 140, Williams & Wilkins, (1992). Web site: http://www.delphion.com/details?pn=US06143752__ •
Method of treating liver disease and like indications with vasodilating agents Inventor(s): McLean; Allan Joseph (South Melbourne, AU) Assignee(s): Pharmacy and Therapeutic Advisory Consultancy Ltd. (london, Gb2) Patent Number: 5,854,233 Date filed: June 20, 1996 Abstract: Liver diseases, such as cirrhosis of the liver, toxic and medicamentary liver damage, a liver-parenchymic disorder or hepatitis, are treated by administering to a human or animal subject in need thereof a therapeutically active or prophylactically effective low dose amount of a vasodilating agent which selectively increases the supply of oxygenated blood to the liver by increasing hepatic arterial inflow. Suitable vasodilating agents include calcium blockers, such as a benzothiazepine derivative, nifedipine, felodipine or verapamil. Excerpt(s): The present invention relates to a method for the treatment of liver disease. The invention also relates to compositions suitable for the use in the treatment of liver disease. Diltiazem is the generic name given to the active component of a composition that is primarily used for the treatment of heart disease. Specifically it is known as 3acetoxy-5-(2(dimethylaminoethyl)-2,3-dihydro-2-(4-methoxy phenyl)-1,5benzothiazepine-4)5H-one. This compound is the active ingredient in the heart treatment drug Cardizem. Cardizem has particular efficacy in the treatment of ischaemic heart disease including angina pectoris and hypertension. Diltiazem is a member of a broad class of benzothiazepine derivatives that are the subject of Australian Patent 426146. The class of compounds are referred to in that specification as having particular utility as anti-depressants, tranquilizers and coronary vasodilators. Web site: http://www.delphion.com/details?pn=US05854233__
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Methods to treat.alpha.1-antitrypsin deficiency Inventor(s): Marcus; Nancy (St. Louis, MO), Perlmutter; David H. (St. Louis, MO) Assignee(s): Washington University in St. Louis (st. Louis, Mo) Patent Number: 6,656,912 Date filed: January 22, 2001 Abstract: Inhibitors of glucosidase, especially those related to castanospermine, are effective in preventing or ameliorating conditions such as liver damage and emphysema that are present in individuals who produce a mutant form of antitrypsin,.alpha.1-ATZ. Also effective in the method of the invention are imino sugars and their reduced forms in general as well as phenylbutyric acid. These compounds enhance the secretion of the mutant form, which retains substantial biological activity, and do not impair its degradation in the endoplasmic reticulum. Excerpt(s): The invention relates to treatment of.alpha.1-antitrypsin (.alpha.1-AT) deficiency in individuals containing a mutant form of.alpha.1-AT exhibiting symptoms of, or at-risk for, liver damage and/or emphysema. In particular, the invention concerns the use of inhibitors of glucosidase and in some instances, of mannosidase in ameliorating these conditions. The enzyme.alpha.1-antitrypsin (.alpha.1-AT) is important in maintaining the condition of lung tissue by virtue of its ability to inhibit neutrophil elastase. If this elastase inhibitor is lacking in the lungs, lung diseases such as emphysema can develop. A substantial number of individuals are deficient in this important enzyme by virtue of the presence of a mutant form of the glycoprotein, designated.alpha.1-ATZ, differing from the wild type by a single amino acid substitution. Although.alpha.1-ATZ this retains approximately 80% of the functional activity of the wild type in inhibiting neutrophil elastase, because it is misfolded and polymerized in the endoplasmic reticulum (ER) of liver cells rather than excreted into the extracellular fluid, it exerts a hepatotoxic effect, especially in infants and children, and is not available in the lungs to carry out its function. There are, however, known pathways for degradation of the mutant.alpha.1-ATZ in the ER--one involving the sequence of stable binding to calnexin, conjugation of ubiquitin to the cytoplasmic tail of the complexed calnexin and degradation of the resulting complex by the proteasome (Qu, D., et al., J. Biol. Chem. (1996) 271:22791-22795). There is also a ubiquitinindependent proteasomal mechanism (Teckman, J. H., et al., Biochem J. (1986) 236:853860). It is apparent that individuals having the genotype which results in the production of the mutant.alpha.1-ATZ would benefit if the secretion of this mutant form of.alpha.1AT could be enhanced, since this mutant form does retain the desired neutrophil elastase inhibition activity. Such individuals would also benefit by any protocol which would result in the enhanced degradation of this mutant form in the ER, thus ameliorating the hepatotoxicity of the misfolded polymer. It has been shown that glucosidase and mannosidase inhibitors inhibit secretion of wild type.alpha.1-AT (Gross, V., et al, Biochem. J. (1986) 236:853-860). It has also been shown that a different mutant.alpha.1-AT which is retained and degraded in the ER,.alpha.1-AT.sub.HONG KONG, is affected by such inhibitors in that ER degradation is accelerated by glucosidase inhibitors and delayed by mannosidase inhibitors (Liu, Y., et al., J. Biol. Chem. (1997) 272:7946-7951; Liu, Y., et al., J. Biol. Chem. (1999) 274:5861-5867). Web site: http://www.delphion.com/details?pn=US06656912__
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Protection against liver damage by HGF Inventor(s): Roos; Filip (Brisbane, CA), Schwall; Ralph (Pacifica, CA) Assignee(s): Genentech, Inc. (so. San Francisco, Ca) Patent Number: 5,654,404 Date filed: April 10, 1995 Abstract: The present invention provides methods for preventing occurrence or progression of liver damage using hepatocyte growth factor. In the methods, a preventatively effective amount of the hepatocyte growth factor is administered to the patient. The hepatocyte growth factor can be administered, for instance, prior to administering a hepatotoxic therapy to the patient. The hepatocyte growth factor can further be administered with activin or transforming growth factor-beta to prevent liver damage. Compositions comprising hepatocyte growth factor and activin antagonist or transforming growth factor-beta antagonist are also provided by the invention. Excerpt(s): The present invention concerns the use of hepatocyte growth factor (HGF) for the prevention of liver damage. Liver damage occurs in a number of acute and chronic clinical conditions, including drug-induced hepatotoxicity, viral infections, vascular injury, autoimmune disease and blunt trauma. In addition, patients subject to inborn errors of metabolism may be at risk for developing liver damage. Symptoms of liver damage occurring as a result of these clinical conditions include, for example, fulminant hepatic failure with cholestasis, hepatic lesions, and liver tissue necrosis, and in many instances, the restoration of normal liver function is vital to the survival of patients. Hepatotoxic compounds can induce almost all types liver injury (Benhamou, JPierre, Liver Cells and Drugs, Chapter 164, pgs. 3-12, Colloque INSERM/John Libbey Eurotext Ltd., edited by A. Guillozo (1988). The susceptibility of the liver to damage by chemical agents may be related to its primary role in drug metabolism or is a consequence of hypersensitivity reactions. Up to 25% of cases of fulminant hepatic failure may be the result of adverse reactions to medical agents. Hepatotoxic compounds are also an important cause of chronic liver disease including fatty liver, hepatitis, cirrhosis and vascular and neoplastic lesions of the liver. (Sinclair et al., Textbook of Internal Medicine, 569-575 (1992) (editor, Kelley; Publisher, J. B. Lippincott Co.). Web site: http://www.delphion.com/details?pn=US05654404__
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Treatment of hepatitis C virus infections with interleukin-10 Inventor(s): Davis; Gary L. (Gainesville, FL), Grint; Paul C. (San Diego, CA), Nelson; David R. (Gainesville, FL) Assignee(s): Schering Corporation (kenilworth, Nj) Patent Number: 6,685,931 Date filed: December 20, 1999 Abstract: The hepatoprotective effect of IL-10 is described, in particular, the use of interleukin-10 in the treatment of liver damage (e.g. fibrosis or cirrhosis) in a difficult-totreat patient afflicted with chronic hepatitis C virus infection who has failed to respond to, or achieve a sustained virologic response to an anti-HCV therapy(e.g., interferon.alpha. in combination with ribavirin).
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Excerpt(s): The invention is directed to the use of interleukin-10 to improve liver histology in patients afflicted with chronic hepatitis C virus infections. In particular, the invention relates to the use of interleukin-10 to reduce hepatic fibrosis in difficult-totreat patients afflicted with chronic hepatitis C virus infections. Chronic hepatitis C is an insidious and slowly progressive disease having a significant impact on morbidity and mortality. While many patients who contract hepatitis C will have subclinical or mild disease, HCV infection causes progressive liver damage in the majority of those infected. At least 80% of the individuals who contract HCV will develop chronic infection and hepatitis, a disease state characterized by fluctuating serum transaminase abnormalities and inflammatory with or without fibrosis lesions on liver biopsy. Twenty to fifty percent of these will eventually progress to cirrhosis and 1-2% will develop liver cancer after a 10-20 year period. Multiple factors influence the hepatitis C virus-host interaction resulting in a unique individual disease pattern. In individuals chronically infected with HCV, there is persistent viremia and liver damage despite the presence of both humoral and cellular responses. The mechanisms responsible for hepatocellular injury are not fully understood. The role of IL-10 in inhibiting liver fibrogenesis has been evaluated in the mouse. Two studies (Louis et al., Heptatology, 1998;28:1607-1615; and Thompson et al., Heptatology, 1998;28:1597-1606) showed that IL-10 knock-out mice develop significantly more severe fibrosis than wild-type mice. Web site: http://www.delphion.com/details?pn=US06685931__
Patent Applications on Liver Damage 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 damage: •
Composition and method for treating nonalcoholic steatohepatitis Inventor(s): Fan, David; (Newport Beach, CA), Hsia, Houn Simon; (Irvine, CA) Correspondence: Lyon & Lyon Llp; Suite 4700; 633 West Fifth Street; Los Angeles; CA; 90071-2066; US Patent Application Number: 20010000028 Date filed: November 29, 2000 Abstract: Nonalcoholic steatohepatitis (NASH) is a disease of the liver characterized by inflammation and damage to the liver cells. Typically, steatohepatitis involves inflammation of the liver related to fat accumulation, and mimics alcoholic hepatitis but is observed in patients who seldom or never consume alcohol. Nonalcoholic steatohepatitis can lead to serious liver damage, and ultimately cirrhosis. The present invention provides methods and compositions useful for the treatment or alleviation of nonalcoholic steatohepatitis and the pharmaceutical formulations for their administration to a human. Specifically, compositions comprised of lecithin, antioxidants and vitamin B complex are administered parenterally, most preferably by oral administration. Specific therapeutic formulations include admixtures of these compounds and specific dosage formulations include daily oral administrations of these compounds in tablet or powder forms.
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This has been a common practice outside the United States prior to December 2000.
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Excerpt(s): 1. This is a divisional of co-pending application Ser. No. 09/205,082, filed on Dec. 4, 1998. The priority of the prior application is expressly claimed, and the disclosure of each of this prior application is hereby incorporated by reference in its entirety. 2. The present invention generally relates to dietary supplements containing lecithin, antioxidants and/or a vitamin B complex to treat liver disease. A preferred embodiment is a composition and the use thereof of a dietary supplement comprising lecithin, at least one antioxidant, and a vitamin B complex administered orally to treat or alleviate nonalcoholic steatohepatitis. 3. The liver is the largest organ in the human body, located in the superior portion of the right upper abdomen. This organ is highly complex and specialized and performs many crucial biochemical functions. The liver is critically involved in the removal of toxins from the body and in the manufacture of proteins including energy storage and blood clotting factors. The liver is also involved in storing minerals, vitamins and glucose in the form of glycogen, which is metabolized in large quantities to provide energy. The liver also plays a role in red blood cell metabolism and the break-down of certain metabolic byproducts in the blood stream. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Diagnostic markers of liver dysfunction Inventor(s): Hugli, Tony E.; (San Diego, CA), Jackson, Craig M.; (San Diego, CA) Correspondence: Lisa A. Haile, J.D., PH.D.; Gray Cary Ware & Freidenrich Llp; 4365 Executive Drive, Suite 1600; San Diego; CA; 92121-2189; US Patent Application Number: 20030087316 Date filed: August 2, 2001 Abstract: The present invention provides methods and kits for detecting and monitoring liver damage in a subject. The methods and kits rely on the correlation between the presence or increase in a kallikrein-like peptidase in a sample from the subject and liver disease. Additionally, the present invention provides in vivo and in vitro methods for detecting toxicity of a therapeutic agent. Methods for detecting, diagnosing, or monitoring liver damage by measuring a panel of components, including kallikrein-like peptidase, along with other blood enzymes and/or complement components are also provided. Excerpt(s): The invention relates generally to methods and kits for detecting liver dysfunction and more specifically to measurement of a peptidase or peptidases synthesized in and secreted from the liver, such as those of the hemostatic and complement systems, as an indicator of liver damage. Currently, methods for detecting liver disease rely on late stage markers that do not identify liver disease before it is in an advanced stage. This has resulted in a deficiency in modern healthcare related to liver disease management, the importance of which is underscored by the fatal nature of liver disease in many instances. Therefore, there is a need for improved methods for liver screening, monitoring, and diagnosis, especially with respect to early stage disease and damage. The magnitude of this need is immense and growing as more organ transplants are performed. As of the year 2000, there were at least 4,000 liver transplants per year in the United States. In 1998, there were almost 25,000 deaths caused by chronic liver disease. Furthermore, there are estimated to be millions of individuals experiencing a variety of liver diseases from advancing chronic liver disease to acute toxicity and viral injury. Finally, there are perhaps even more individuals with various stages of liver disease that remain undetected. Consequently, a reliable method for detecting early onset liver damage or monitor progressive liver damage or repair is needed. Such an
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assay should find wide application in research, pharmaceutical product evaluation, development and clinical medicine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
L-ergothioneine, milk thistle, and s-adenosylmethionine for the prevention, treatment and repair of liver damage Inventor(s): Corson, Barbara E.; (Fawn Grove, PA), Henderson, Todd R.; (Jarrettsville, MD) Correspondence: Paul J. Berman, EAQ.; Covington & Burling; 1201 Pennsylvania Avenue, N.W.; Washington; DC; 20004-2401; US Patent Application Number: 20010000472 Date filed: December 8, 2000 Abstract: This invention provides therapeutic compositions and combinations for the protection, treatment and repair of liver tissue. The invention relates to novel compositions and combinations comprising two or more compounds selected from the group consisting of S-adenosylmethionine, L-ergothioneine, and a substance selected from the group consisting of constituents of Milk thistle (Silybum marianum), silymarin and active components of silymarin, whether naturally, synthetically, or semisynthetically derived, and to methods of preventing and treating liver disease and of repairing damaged liver tissue. The invention also provides a method of administering these compositions and combinations to humans or animals in need thereof. Excerpt(s): 1. The present application is a continuation-in-part application of U.S. patent application Ser. No. 09/256,352, filed Feb. 24, 1999, the disclosure of which is hereby incorporated by reference herein in its entirety. That application claimed priority to provisional application: "L-ERGOTHIONEINE, MILK THISTLE, AND SADENOSYLMETHIONINE FOR LIVER FAILURE," U.S. Ser. No. 60/076,347, filed Feb. 27, 1998, the disclosure of which is hereby incorporated by reference herein in its entirety. 2. The present invention relates to compositions and combinations for the protection, treatment and repair of liver tissues in humans and animals. 3. The liver is an extremely important organ. As the major metabolic organ of the body, the liver plays some role in almost every biochemical process, including the deamination of amino acids and the formation of urea, the regulation of blood sugar through the formation of glycogen, the production of plasma proteins, the production and secretion of bile, phagocytosis of particulate matter from the splanchnic (intestinal) circulation, and the detoxification and elimination of both endogenous and exogenous toxins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for treating carbon tetra-cloride induced liver damage by administering morinda citrifolia Inventor(s): Jensen, Claude Jarakae; (Cedar Hills, UT), Su, Chen; (West Jordan, UT), Wang, Mian-Ying; (Rockford, IL) Correspondence: Kirton And Mcconkie; 1800 Eagle Gate Tower; 60 East South Temple; P O Box 45120; Salt Lake City; UT; 84145-0120; US Patent Application Number: 20030086990 Date filed: December 31, 2001 Abstract: There is disclosed a method for preventing CCL4 (carbon tetracloride) induced liver damage comprising the prophylactic administration of extracts of Morinda citrifolia. The Morinda citrifolia may be administered in solid or liquid forms. Several regimens are disclosed including the administration of 2 ounces twice daily in a liquid form such as that sold by Morinda, Inc. Excerpt(s): The present invention relates to methods and formulations for treating liver damage, and particularly to treating liver damage and preventing CCL4 (carbon tetracloride) induced liver damage comprising the prophylactic administration of extracts of Morinda citrifolia. Liver damage from hepatitis C, alcohol, or carbon tetracloride is well documented. However, many of the treatments result in undesirable side effects. Carbon tetrachloride (CC14) is a common environmental pollutant and liver carcinogen. CC14 is leached into the soil through agricultural run-off, spills, landfill contamination, and dumping illegal. Surface waters become contaminated due to industrial and agricultural activities, wastewater release, particularly from iron and steel manufacturing, as well as other major industries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods of treating liver disease and liver damage with growth hormone and foxM1B Inventor(s): Adami, Guy; (Brookfield, IL), Costa, Robert H.; (Oak Park, IL), KrupczakHollis, Katherine; (Chicago, IL), Tan, Yongjun; (Arlington Heights, IL), Wang, Xinhe; (Chicago, IL) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20020187936 Date filed: May 17, 2002 Abstract: The invention provides a method of treating liver damage or disease in a patient by stimulating liver regeneration. Specifically, the invention provides a method of inducing liver cell proliferation comprising contacting liver cells that express FoxM1B protein with growth hormone. The invention also provides methods of screening for compounds that induce FoxM1B protein expression, nuclear localization, or both expression and nuclear localization. The invention further provides pharmaceutical compositions comprising selected compounds and methods of using such compositions. Excerpt(s): This application is related to U.S. provisional application Serial No. 60/291,789, filed May 17, 2001, No. 60/305,821, filed Jul. 16, 2001, and No. 60/315,484, filed Aug. 28, 2001. One important function of mammalian liver is to detoxify harmful compounds that enter the body. In the liver, toxic substances may be cleared from the
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body by phagocytosis, secretion into the bile, or by chemical modification of the compound to facilitate elimination by the kidneys. Other functions of the liver include storing vitamins, producing cholesterol and bile to assist digestion, converting excess glucose into glycogen, and releasing glucose into the blood during fasting. The liver is also responsible for secreting all serum carrier proteins and proteins involved in blood coagulation. A healthy liver, therefore, is an important contributor to the overall health of an animal or human individual. Environmental and dietary toxins constantly bombard the liver throughout a lifetime. The potential for liver damage increases with time and as the stress of removing these toxins increases. The mammalian liver is capable of completely regenerating itself in response to such liver damage (Fausto et al., 1995, FASEB J 9: 1527-1536; Michalopoulos et al., 1997, Science 276: 60-66; Taub, 1996, FASEB J. 10: 413-427). However, excessive exposure to toxins such as alcohol or certain drugs can cause severe liver damage leading to disease. During aging, the ability of the liver to regenerate decreases and liver damage and disease becomes more severe and more difficult to treat. Thus, the ability to stimulate hepatocyte proliferation and restore the regenerative potential of these liver cells would prove invaluable in treating liver diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods to treat alpha1-antitrypsin deficiency Inventor(s): Marcus, Nancy; (St. Louis, MO), Perlmutter, David H.; (St. Louis, MO) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20020006909 Date filed: January 22, 2001 Abstract: Inhibitors of glucosidase, especially those related to castanospermine, are effective in preventing or ameliorating conditions such as liver damage and emphysema that are present in individuals who produce a mutant form of antitrypsin,.alpha.1-ATZ. Also effective in the method of the invention are imino sugars and their reduced forms in general as well as phenylbutyric acid. These compounds enhance the secretion of the mutant form, which retains substantial biological activity, and do not impair its degradation in the endoplasmic reticulum. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119(e) to provisional application No. 60/177,472 filed Jan. 21, 2000 and to application No. 60/177,392 filed Jan. 20, 2000. The contents of these applications are incorporated herein by reference. The invention relates to treatment of.alpha.1-antitrypsin (.alpha.1-AT) deficiency in individuals containing a mutant form of.alpha.1-AT exhibiting symptoms of, or at-risk for, liver damage and/or emphysema. In particular, the invention concerns the use of inhibitors of glucosidase and in some instances, of mannosidase in ameliorating these conditions. The enzyme.alpha.1-antitrypsin (.alpha.1-AT) is important in maintaining the condition of lung tissue by virtue of its ability to inhibit neutrophil elastase. If this elastase inhibitor is lacking in the lungs, lung diseases such as emphysema can develop. A substantial number of individuals are deficient in this important enzyme by virtue of the presence of a mutant form of the glycoprotein, designated.alpha.1-ATZ, differing from the wild type by a single amino acid substitution. Although.alpha.1-ATZ this retains approximately 80% of the functional activity of the wild type in inhibiting neutrophil elastase, because it is misfolded and polymerized in the endoplasmic reticulum (ER) of liver cells rather than excreted into the extracellular fluid, it exerts a
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hepatotoxic effect, especially in infants and children, and is not available in the lungs to carry out its function. There are, however, known pathways for degradation of the mutant.alpha.1-ATZ in the ER--one involving the sequence of stable binding to calnexin, conjugation of ubiquitin to the cytoplasmic tail of the complexed calnexin and degradation of the resulting complex by the proteasome (Qu, D., et al., J. Biol. Chem. (1996) 271:22791-22795). There is also a ubiquitin-independent proteasomal mechanism (Teckman, J. H., et al., Biochem J. (1986) 236:853-860). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Omega-cycloalkyl-prostaglandin E2 derivatives Inventor(s): Ohuchida, Shuichi; (Mishima-gun, JP), Tani, Kousuke; (Mishima-gun, JP) Correspondence: Stevens Davis Miller & Mosher, Llp; 1615 L Street, NW; Suite 850; Washington; DC; 20036; US Patent Application Number: 20030186939 Date filed: September 11, 2002 Abstract: A.omega.-cycloalkyl-prostaglandin E.sub.2 derivatives of the formula (I) 1wherein R is carboxy or hydroxymethyl; R.sup.1 is oxo, methylene or halogen atom; R.sup.2 is H, OH or C1-4 alkoxy; R.sup.3 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkoxy, C3-7 cycloalkyl, phenyl, or phenyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkyl, C1-4 alkoxy, nitro, trifluoromethyl; n is 0-4;and non-toxic salt thereof, prodrug thereof and cyclodextrin clathrate thereof can strongly bind on EP.sub.2 subtype receptor. Therefore, they are useful for prevention and/or treatment of immune disease (autoimmune disease, organ transplantation, etc.), asthma, abnormal bone formation, neuron cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc. Excerpt(s): wherein all the symbols are the same meaning as hereafter defined, non-toxic salt thereof, prodrug thereof and cyclodextrin clathrate thereof. Prostaglandin E.sub.2 (abbreviated as PGE.sub.2 hereafter) has been known as metabolite in the arachidonate cascade. It has been known that PGE.sub.2 has cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect of digestive peristalsis, an awakening effect, a suppressive effect of gastric acid secretion, hypotensive activity and diuretic activity etc. In a recent study, it was found that PGE.sub.2 receptor was divided into some subtype which possess different physiological roles from each other. At present four receptor subtype are known and they are called as EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4 (Negishi M. et al, J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with liver damage, 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:
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Under “Issued Patents,” click “Quick Search.” Then, type “liver damage” (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 damage. You can also use this procedure to view pending patent applications concerning liver damage. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON LIVER DAMAGE Overview This chapter provides bibliographic book references relating to liver damage. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on liver damage 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 damage” (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 damage: •
Managing the Side Effects of Chemotherapy and Radiation Therapy: A Guide for Patients and Their Families. 3rd ed Source: San Francisco, CA: UCSF Nursing Press. 1996. 198 p. Contact: Available from UCSF Nursing Press. 521 Parnassus Avenue, Room N-535C, San Francisco, CA 94143-0608. (415) 476-4992 or (415) 476-2626. Fax (415) 476-6042. PRICE: $20.00 plus $6.00 shipping and handling. ISBN: 0943671120. Summary: This book is designed to help patients and their families learn to cope with the many side effects of cancer chemotherapy and radiation therapy. The chemotherapy section lists every frequently used cancer drug and common side effects of each. This information is first presented in chart format, then discussed in some detail. Suggestions for managing each side effect are included. The section on side effects includes a description of the problem, its likely duration, recommended self-care measures, and when to consult with a health care provider. The remainder of the book discusses the
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common side effects of radiation therapy, with the same type of information and in the same format. Side effects particularly relevant to the digestive system include abdominal pain, constipation, diarrhea, liver damage, sore mouth or difficulty swallowing, nausea and vomiting, and stomach irritation and ulcers. A subject index concludes the book.
Chapters on Liver Damage In order to find chapters that specifically relate to liver damage, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and liver damage 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 damage” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on liver damage: •
Hepatitis and Dialysis Source: in Lameire, N. and Mehta, R.L., eds. Complications of Dialysis. New York, NY: Marcel Dekker, Inc. 2000. p. 673-696. Contact: Available from Marcel Dekker, Inc. Cimarron Road, P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (845) 796-1919. Fax (845) 796-1772. E-mail:
[email protected]. International E-mail:
[email protected]. Website: www.dekker.com. PRICE: $250.00 plus shipping and handling. ISBN: 0824788710. Summary: Patients on maintenance hemodialysis are at increased risk for parenterally transmitted hepatitis viruses. This chapter on hepatitis and dialysis is from a book that offers a comprehensive, multidisciplinary resource for the nephrologist and caregiver providing dialysis, covering all aspects of dialysis therapies and their complications. The authors of this chapter focus mainly on hepatitis B virus (HBV) and hepatitis C (HCV), which remain the most problematic viral hepatic (liver) infections in hemodialysis patients; hepatitis G virus (HGV) is discussed briefly in the final section of the chapter. For each of these types, the authors consider pathogenesis, transmission and preventive measures, epidemiology (prevalence and incidence), vaccination, and implications for kidney transplantation. Besides the known parenterally transmitted hepatitis viruses, other yet undefined but potentially dangerous viruses may exist. Every nephrologist (kidney specialist) faces some dialysis patients who have inexplicable liver disease in which no responsible virus has been identified. The authors stress that it is therefore advisable to consider all patients as potentially infectious, especially since the level of transaminase is not always a reliable marker for the detection of liver damage in the dialysis population. Isolation procedures are warranted not only for viral infection but also for bacterial infection such as certain drug resistant strains. 2 figures. 4 tables. 243 references.
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Iron Overload States Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.399-411. 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:
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[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: The causes of iron overload can be broadly separated into those with a clear genetic mechanism, those associated with another pathology, and a small group of intermediate conditions where there appears to be an interplay between genetic and acquired mechanisms. Iron overload as a result of liver or hematological (blood) disease is not uncommon and genotyping now allows these to be clearly separated from genetic hemochromatosis. This chapter on iron overload states is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers normal iron metabolism, iron overload and the resulting liver damage, genetic hemochromatosis, and other iron storage diseases, including non-HFE-related inherited iron overload, dysmetabolic syndrome, erythropoietic siderosis, late stage cirrhosis, chronic viral hepatitis, non-alcoholic fatty liver disease, neonatal hemochromatosis, African iron overload (Bantu siderosis), porphyria cutanea tarda, hemodialysis, acaeruloplasminemia, and transferrin deficiency. 6 figures. 1 table. 99 references. •
Alcoholic Liver Disease Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 707-713. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter from a gastroenterology textbook covers alcoholic liver disease (ALD), defined as the development of liver damage following longterm heavy alcohol consumption. In terms of health costs, it equals the treatment of many cancers. This is not yet taking into account the social costs of chronic alcoholism, the silent forerunner of (ALD), in terms of loss of productivity and disruption to personal and family lives. The authors first detail the management of chronic alcoholism, the treatment of alcohol withdrawal, and longterm sobriety maintenance. The authors then outline three types of ALD: fatty liver, alcoholic hepatitis, and liver cirrhosis. Fatty liver is usually a benign, reversible condition that disappears on abstinence from alcohol. Alcoholic hepatitis can present acutely with high mortality or be present in chronic form; it is characterized by liver cell necrosis and inflammation. The pivotal factor in the treatment of alcoholic liver disease is prolonged abstinence from alcohol and good nutritional support, together with specific drug therapies for certain indications. The authors also briefly consider the use of liver transplantation to treat patients with alcoholic cirrhosis. 2 tables. 10 references.
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Amyloidosis, Metabolic Diseases, Drug-Induced and Chemical-Induced Liver Injuries Source: in Okuda, K., ed.,et al. Hepatobiliary Diseases: Pathophysiology and Imaging. Malden, MA: Blackwell Science, Inc. 2001. p. 197-211. 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: $275.00. ISBN: 0632055421.
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Summary: This chapter on amyloidosis, metabolic diseases, drug-induced and chemicalinduced liver injuries is from a textbook that familiarizes the reader with various imaging modalities, the information they provide, and the merits of each, in order to facilitate the combined use of different imaging techniques in the diagnosis and management of hepatobiliary (liver and bile tract) diseases. Amyloidosis is a disorder of protein metabolism in which an autologous (from the patient's own body) protein forms fibrils by polymerization and is then deposited intercellularly. Amyloid deposits rarely regress and tend to increase, disrupting the structure and function of the tissue or organ (including the liver) in which they lie. The author discusses primary and secondary amyloidosis, familial (hereditary) amyloidosis, and amyloidosis of the liver. There are many storage diseases that are caused by deficiency of one particularly enzyme; they are grouped into lipoid storage diseases and glycogen storage diseases. Inherited hyperbilirubinemia (high levels of bilirubin in the blood) disorders include Gilbert's syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and Rotor's syndrome. Liver injury inflicted by drugs and chemicals is generally characterized as hepatocellular (liver cell) injury, cholestatic (gallbladder or bile duct) injury, or mixed injury. However, there are no specific imaging features associated with chemical induced liver damage, so the authors do not go into detailed descriptions of these disorders. The final section in the chapter covers peliosis hepatitis, defined by the presence of cystic blood-filled spaces in the liver. 17 figures. 2 tables. 28 references. •
Drug-Induced Liver Disease Source: in Textbook of Gastroenterology. 4th ed. [2-volume set]. Hagerstown, MD: Lippincott Williams and Wilkins. 2003. p. 2352-2365. 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: This chapter on drug induced liver disease is from a comprehensive gastroenterology textbook that provides an encyclopedic discussion of virtually all the disease states encountered in a gastroenterology practice. In this chapter, the authors cover epidemiology, drug metabolism and mechanisms of hepatotoxicity (liver damage by toxin), classification of hepatotoxic agents, types of drug reactions (clinical pictures), treatment, the criteria for causal assessment of drug-induced liver injury, lessons from drugs withdrawn from the market, the drug approval process, hepatotoxicity in the patient with chronic liver disease, and a clinician's guide to handling new drugs. The authors stress that the exact number of drug-induced liver injuries per year in the United States is unknown, but the severity of many of these cases and the tragedy involved in a presumed preventable injury makes it imperative that all sensible precautions be taken to avoid such incidents. The chapter is illustrated with black-andwhite graphs and drawings. 4 figures. 9 tables. 161 references.
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Hepatitis C Source: in Hagan, P.T., ed. Mayo Clinic Guide to Self-Care: Answers for Everyday Health Problems. New York, NY: Kensington Publishers. 1999. p. 178-179. Contact: Available from Mayo Clinic. 200 First Street, S.W., Rochester, MN 55905. (800) 291-1128 or (507) 284-2511. Fax (507) 284-0161. Website: www.mayo.edu. PRICE: $16.95 plus shipping and handling. ISBN: 0962786578. Summary: This chapter on hepatitis C is from a self care handbook on everyday health problems published by the Mayo Clinic. The handbook offers readers a guide to
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symptoms, diagnosis, and treatment for common problems (particularly self care strategies and tips for handling these problems in children). Hepatitis C is a virus that causes inflammation of the liver. Nearly 4 million Americans have the virus, but many of them don't know it as the symptoms can be very subtle. Generally, hepatitis C is spread through contact with blood contaminated with the virus (in rare cases, it's transmitted sexually). About 15 to 20 percent of people infected with hepatitis C fight off the virus on their own without liver damage. For the rest, the disease settles in and slowly attacks the liver. Anywhere from 20 to 50 percent of people with chronic hepatitis develop cirrhosis (scarring) of the liver, usually within the first 2 decades after infection. Ultimately, liver cancer or liver failure occurs in about half of those people who develop cirrhosis. Recommended lifestyle changes for people with hepatitis C can include eliminating alcohol consumption, avoiding medications that may carry a risk of liver damage, and maintaining a healthful lifestyle (diet, exercise, and rest). One section discusses the use of interferon alpha, a drug that inhibits viral replication and that can be effective in approximately 20 percent of people with hepatitis C. One sidebar reviews the people who should be tested or screened for hepatitis C. The book is focused on how to prevent illness, how to detect illness before it becomes a serious and costly problem, and how to avoid unnecessary trips to the clinic or emergency room. •
Other Causes of Parenchymal Liver Disease Source: in Beckingham, I.J., ed. ABC of Liver, Pancreas and Gallbladder. London, UK: BMJ Publishing Group. 2001. p.15-17. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail:
[email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. ISBN: 0727915312. Summary: This chapter on other causes of parenchymal (in the body of the organ) liver disease is from an atlas of the liver, pancreas and gallbladder. Topics covered include autoimmune hepatitis; metabolic causes of liver disease, including hemochromatosis (iron overload) and Wilson's disease (copper deposition); drug related hepatitis, including paracetamol and idiosyncratic drug reactions; and cholestatic nonobstructive jaundice, including primary biliary cirrhosis and primary sclerosing cholangitis. The author notes that most drugs have the potential to cause liver injury and 2 to 7 percent of admissions with nonobstructive jaundice are for drug related hepatitis. Herbal remedies and illegal drugs can also cause jaundice and liver damage. The chapter concludes with summary points of the concepts discussed. 6 figures. 3 tables.
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Liver and Gallbladder Source: in Kelly, R.B., ed. Family Health and Medical Guide. Dallas, TX: Word Publishing. 1996. p. 201-206. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. PRICE: $30.00 for members; $35.00 for non-members; plus shipping and handling. ISBN: 0849908396. Summary: This chapter on the liver and gallbladder is from a family health and medical guide. The chapter describes the functions of the liver, including detoxification of substances such as drugs and alcohol; metabolism of carbohydrates, proteins, and fats; conversion of digested food into energy; storage of substances such as iron and vitamins A, B12, and D; and production of bile, which breaks down fats and helps digest them. The chapter then covers problems of the liver and gallbladder, including cirrhosis
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(alcoholic, biliary, postnecrotic, and postviral), gallbladder cancer, gallstones, hepatitis, liver abscess, and liver cancer. For each topic, the authors explain symptoms, diagnostic tests, treatment options, and prevention. One sidebar discusses jaundice; another summarizes the three stages of liver damage caused by excessive alcohol intake. 1 figure. •
Treatment of Chronic Hepatitis C: Transplant Recipients Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 263-293. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on the treatment of chronic hepatitis C in transplant recipients is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient was a 45 year old female who presented with chronic hepatitis C with cirrhosis (liver scarring). She was referred for liver transplantation 1 year after diagnosis, due to deterioration of her condition. Although her hepatitis recurred after transplant and contributed to three serious episodes of rejection, the patient is now clinically stable. Recurrent hepatitis occurs in 40 to 80 percent of patients; it is usually found during the first year posttransplant. Recurrence of HCV infection leads to cirrhosis in 10 percent of patients 5 years after transplant. The clinical presentation of HCV recurrence and acute graft infection after transplantation varies from asymptomatic or minimal liver damage to an influenza like syndrome with or without jaundice. Risk factors involved in a more severe recurrence are still being studied. Immunosuppressive medications result in increased viral proliferation and a worse outcome of hepatitis C recurrence. Histological features are important, but can be confusing in differentiating HCV recurrence from other post transplantation complications such as acute rejection. Combination therapy with inferon and ribavirin may lead to an improved liver histology in patients with severe recurrence, but few patients have a sustained viral response and further advances in the management of this group of patients are required. 1 figure. 4 tables. 107 references.
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Chronic Viral Hepatitis Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume Two. Philadelphia, PA: Current Medicine. 1999. p. 839-849. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Viral infection is the most common cause of acute and chronic liver disease in the world. Chronic viral hepatitis is defined as more than 6 months of clinical, biochemical, or histologic evidence of liver damage in a patient with serologic markers of infection with a hepatitis virus known to cause chronic liver disease. This chapter on chronic viral hepatitis (liver infection) is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. Chronic infection with hepatitis virus B, C, D, or G may produce an asymptomatic carrier state or active liver disease, including chronic
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hepatitis, cirrhosis, and hepatocellular carcinoma (HCC, liver cancer). The authors review the epidemiology, diagnosis, natural history, treatment, and prevention of chronic HBV, HCV, HDV, and HGV infections. The main aim of treatment of chronic HBV infection is to suppress replication of the virus before there is significant, irreversible liver damage. Treatment strategies include the use of interferon alpha and other antiviral agents; safe and effective vaccines are available for the prevention of HBV infection. In people with hepatitis C virus (HCV) infections, 85 percent are likely to progress to chronic infection. The goals of treatment of patients with chronic hepatitis C are to eradicate HCV, to induce remission of liver disease, and to prevent the development of cirrhosis and HCC. 5 figures. 6 tables. 34 references.
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CHAPTER 7. MULTIMEDIA ON LIVER DAMAGE Overview In this chapter, we show you how to keep current on multimedia sources of information on liver damage. 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 damage is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “liver damage” 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 damage” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on liver damage: •
Cirrhosis of the Liver Source: Los Angeles, CA: National Health Video, Inc. 1998. (videocassette). Contact: Available from National Health Video, Inc. 12021 Wilshire Blvd., Suite 550, Los Angeles, CA 90025. (800) 543-6803. Fax (310) 477-8198. E-mail:
[email protected]. PRICE: $89.00 plus shipping and handling. Summary: This health education videotape is designed to convince viewers of the liver damage caused by alcohol intake. Narrated by a registered dietitian, the program first briefly reviews the anatomy of the liver and then describes the liver's functions: making clotting factors, supporting the immune system, filtering out chemical and alcohol toxins (regardless of how they enter the body), maintaining glycogen (stored food energy), aiding digestion of fats, protein and carbohydrates, and making bile for digesting fats and accessing vitamins. The main factor in keeping the liver healthy is the avoidance of alcohol, but the program also discusses the importance of a healthy diet and regular exercise. The program then focuses on cirrhosis, a condition in which
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normal liver cells are replaced by scar tissue. The program offers mortality statistics and reviews the causes of cirrhosis, including hepatitis, genetic disease, drug effects, and alcohol (which causes 75 percent of cirrhosis cases). There are no adequate warning signs that become apparent before the liver has been damaged. The program discusses the consequences of cirrhosis, including malnutrition, hepatic encephalopathy (ammonia induced mental impairment), swollen abdomen (ascites), fatty liver (in which fat cells replace normal liver cells), and reduced ability to manage medications and toxins. A final section discusses liver failure and liver transplantation, emphasizing that there are never enough donor livers available and that people who have alcohol induced liver disease are often not acceptable transplant candidates. The program features interviews and scenes with patients and physicians. •
What You Really Need to Know About Hepatitis Source: [Toronto, Ontario, Canada]: Videos for Patients. 1995. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $99.00 (Canadian); contact producer for current price in American dollars. Order Number VFP024. Summary: This patient education videotape provides information about hepatitis. The videotape begins with a brief sketch featuring comedian John Cleese and narrator Dr. Robert Buckman illustrating the difficulties sometimes experienced by patients during the traditional doctor's explanation. Topics include the main types of hepatitis (hepatitis A, B, and C), how hepatitis viruses are transmitted, symptoms, diagnostic considerations, what to do while an attack of hepatitis is happening, treatment options, how to reduce the risk of transmitting or contracting hepatitis, long-term liver damage caused by hepatitis, and immunization against hepatitis. Dr. Buckman presents the medical facts, using models, simple diagrams, and graphics to supplement his explanation, and avoiding medical jargon as much as possible.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “liver damage” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on liver damage: •
Substance Use/Multiple Diagnosis. National Conference on Women and AIDS/HIV Infection; Washington, D.C., December 13-14, 1990 Contact: Triad Media Group, PO Box 778, Frederick, MD, 21701, (301) 663-1471. Summary: This sound recording is a presentation from the National Conference on Women and AIDS/HIV Infection held December 13-14, 1990, in Washington, D.C. It examines the relationship between substance abuse and Human immunodeficiency virus (HIV) infection. Acquired immunodeficiency syndrome (AIDS) and alcohol and drug abuse go hand-in-hand, according to the first speaker. Addiction is inherited, and the families it afflicts are dysfunctional. Women in such families need multiple,
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systemic, and comprehensive support services and treatment. The second speaker discusses results of antibody tests on women who came to an alcohol detoxification center. The seropositive rate was much higher than normal. Since alcohol abuse can cause liver damage, it may also prevent individuals from being treated with certain drugs which can also adversely affect liver function. Relapse after treatment for alcohol addiction and fetal alcohol syndrome are two other major problems. The third speaker describes HIV-brain disease, or dementia, and lists several other factors which may affect a patient's mental state. These are opportunistic infections which may affect the brain, medication side effects, and drug interactions. A good client history is useful to distinguish the cause of the problem. The fourth speaker explains the types of mental disorders common to substance abusers, the stages of addiction treatment and interventions necessary in each one, and the need for suicidal assessment and support groups.
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CHAPTER 8. PERIODICALS AND NEWS ON LIVER DAMAGE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover liver damage.
News Services and Press Releases One of the simplest ways of tracking press releases on liver damage 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 damage” (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 damage. 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 damage” (or synonyms). The following was recently listed in this archive for liver damage: •
US group sues FDA over drug linked to liver damage Source: Reuters Industry Breifing Date: March 15, 2004
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Group sues FDA over drug linked to liver damage Source: Reuters Health eLine Date: March 15, 2004
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New therapies for liver damage on the horizon Source: Reuters Health eLine Date: February 06, 2003
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Man's herbal tea use linked to liver damage Source: Reuters Health eLine Date: July 17, 2002
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Germany bans kava due to potential for liver damage Source: Reuters Industry Breifing Date: June 17, 2002
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Chinese weight-loss drug believed to be linked to cases of liver damage in Singapore Source: Reuters Industry Breifing Date: May 17, 2002
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Chinese slimming drug linked with liver damage in Singapore Source: Reuters Medical News Date: May 17, 2002
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Chinese drug linked to liver damage in Singapore Source: Reuters Health eLine Date: May 16, 2002
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Smoking can aggravate hepatitis C liver damage Source: Reuters Health eLine Date: April 10, 2002
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FDA warns of Kava link to liver damage Source: Reuters Industry Breifing Date: March 26, 2002
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Supplement linked to seven cases of liver damage Source: Reuters Health eLine Date: March 18, 2002
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Liver damage reported in man taking diabetes drug Source: Reuters Health eLine Date: March 18, 2002
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Depleted uranium may cause liver damage--study Source: Reuters Medical News Date: March 12, 2002
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Maxim says drug can stop alcohol-related liver damage Source: Reuters Medical News Date: March 04, 2002
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Maxim drug stops alcohol-related liver damage in preclinical study Source: Reuters Industry Breifing Date: March 04, 2002
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Company says drug stops liver damage from alcohol Source: Reuters Health eLine Date: March 04, 2002
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Alcohol compounds liver damage in hepatitis C Source: Reuters Health eLine Date: January 15, 2001
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “liver damage” (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 damage” (or synonyms). If you know the name of a company that is relevant to liver damage, 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 damage” (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
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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 damage” (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 damage: •
Immune Suppressive Medications: Their Benefits and Side Effects Source: Lupus News. 18(2): 12-13. Spring 1998. Summary: This newsletter article provides people who have lupus with information on the use and side effects of immunosuppressive drugs such as azathioprine, cyclophosphamide, and cyclosporin A. Azathioprine interferes with DNA synthesis by causing rapidly growing immune cells to die. Common side effects of azathioprine include nausea and vomiting, bone marrow depression, and liver damage. Cyclophosphamide is given either orally or intravenously, and it works by inhibiting DNA replication and killing immune cells. The adverse effects of cyclophosphamide include hair thinning or complete hair loss during therapy, nausea, vomiting, bone marrow depression, bladder irritation or injury, fertility problems, and tumor formation. Cyclosporin A is generally not used to treat lupus and is reserved for patients who have failed more conventional therapy. The article also provides recommendations for people who may need to begin treatment with immunosuppressive drugs.
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Hepatitis C: Shedding Light on the Shadow Epidemic Source: Harvard Health Letter. 24(9): 1-3. July 1999. Contact: Available from Harvard Medical School Health Publications Group. Harvard Health Letter, P.O. Box 420300, Palm Coast, FL 32142-0300. (800) 829-9045. E-mail:
[email protected]. Summary: When people learn they have hepatitis C, their initial reaction is often disbelief and confusion. Many of those carrying this silent and sometimes deadly bloodborne virus feel perfectly healthy and learn of their infection only after donating blood or having routine blood tests. This newsletter article reports on a recent effort by the Centers for Disease Control and Prevention (CDC) to improve people's awareness by launching a hepatitis C public information campaign. People who are not now infected with HCV are not likely to get it unless they use IV drugs. Improved blood screening has made the risk of contracting HCV from a transfusion exceedingly low. However, most people who have HCV don't realize they're carrying the virus, which can lurk in the liver for decades before symptoms appear. It is important for people to know they have HCV so they can avoid alcohol (which accelerates liver damage), undergo frequent blood tests to monitor their liver function, and consider treatments with antiviral drugs that can reduce or eliminate the virus in some people. The majority of carriers remain fairly healthy, but at least 20 to 30 percent eventually develop cirrhosis (scarring of the liver caused by prolonged inflammation). Several blood tests can determine if a person has been infected with HCV. The author describes these tests and then briefly outlines the treatment options for HCV. One sidebar offers the contact information (telephone numbers and websites) for three resource organizations. 2 references.
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Academic Periodicals covering Liver Damage Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to liver damage. In addition to these sources, you can search for articles covering liver damage that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for liver damage. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with liver damage. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to liver damage: Acetaminophen and Salicylates •
Systemic - U.S. Brands: Excedrin Extra-Strength Caplets; Excedrin ExtraStrength Tablets; Excedrin Migraine; Gelpirin; Goody's Fast Pain Relief; Goody's Headache Powders; Rid-A-Pain Compound; Saleto; Supac; Vanquish Caplets http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203003.html
Acetaminophen, Sodium Bicarbonate, and Citric Acid •
Systemic - U.S. Brands: Bromo-Seltzer http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202005.html
Butalbital and Acetaminophen •
Systemic - U.S. Brands: Amaphen; Anolor-300; Anoquan; Arcet; Bancap; Bucet; Butace; Conten; Dolmar; Endolor; Esgic; Esgic-Plus; Ezol; Femcet; Fioricet; Isocet; Medigesic; Pacaps; Pharmagesic; Phrenilin; Phrenilin Forte; Repan; Sedapap; Tencet; Tencon; Triad; Triaprin; Two-Dyne http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202102.html
Dantrolene •
Systemic - U.S. Brands: Dantrium http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202181.html
Isometheptene, Dichloralphenazone, and Acetaminophen •
Systemic - U.S. Brands: Amidrine; Duradrin; I.D.A; Iso-Acetazone; Isocom; Midchlor; Midrin; Migquin; Migrapap; Migratine; Migrazone; Migrend; Migrex; Mitride http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202306.html
Isoniazid •
Systemic - U.S. Brands: Laniazid; Nydrazid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202307.html
Narcotic Analgesics and Acetaminophen •
Systemic - U.S. Brands: Allay; Anexsia 5/500; Anexsia 7.5/650; Anolor DH 5; Bancap-HC; Capital with Codeine; Co-Gesic; Darvocet-N 100; Darvocet-N 50; DHCplus; Dolacet; Dolagesic; Duocet; E-Lor; Endocet; EZ III; Hycomed; HycoPap; Hydrocet; Hydrogesic; HY-PHEN; Lorcet 10/650 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202392.html
Trientine •
Systemic - U.S. Brands: Syprine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202575.html
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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. 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/
11
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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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
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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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
•
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 damage” (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 18824 63 984 54 156 20081
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 damage” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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.
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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 damage 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 damage. 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 damage. 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 damage”:
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Other guides Bile Duct Diseases http://www.nlm.nih.gov/medlineplus/bileductdiseases.html Cirrhosis http://www.nlm.nih.gov/medlineplus/cirrhosis.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 damage. 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: •
Silent Killers in the Asian and Pacific Islander American Communities Source: Stanford, CA: Asian Liver Center. 200x. 8p. Contact: Available from Asian Liver Center. The Asian Liver Center at Stanford University, 300 Pasteur Drive, H3680, Stanford, CA 94305. (650) 725-4837. Fax: (650) 7230006. Website: http://liver.stanford.edu/. PRICE: Full-text available online at no charge. Summary: Although hepatitis B is uncommon in the majority of the United States population, Asian and Pacific Islander Americans have a disproportionately high incidence of the disease. Hepatitis B is a virus that is transmitted mainly by blood; the virus causes liver damage and can cause liver cancer. This brochure, written in English and Vietnamese, reviews the risk factors for hepatitis B, then discusses the role of vaccination, transmission, silent progression of the disease (lack of symptoms), chronic hepatitis, liver cancer, and the role of screening. The brochure also describes the Jade Ribbon Campaign, a program designed to help fight hepatitis B and liver cancer. The brochure includes the contact information for the Asian Liver Center (http://liver.Stanford.edu).
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•
Silent Killers in the Asian and Pacific Islander American Community Source: Standford, CA: Asian Liver Center. 2001. 6 p. Contact: Available from Asian Liver Center. 300 Pasteur Drive, H3680, Stanford, CA 94305. (650) 725-4837. Website: http://liver.stanford.edu/. PRICE: Single copy free. Summary: Although uncommon in the majority of the United States population, hepatitis B is disproportionately high in Asian and Pacific Islander Americans. Hepatitis B is a virus transmitted mainly by blood that causes liver damage and that can cause liver cancer. This bilingual brochure, written in English and Chinese, cautions Asian and Pacific Islanders (API) about their increased risk of hepatitis B. The brochure reviews the hazards of hepatitis B, transmission of the disease, why hepatitis B is often not diagnosis, and recommendations for readers regarding testing, vaccination, and education. Depending on the country of origin, 5 to 15 percent of API immigrants are hepatitis B carriers. Many chronic hepatitis B carriers have no symptoms and feel perfectly healthy. However, transmission of the hepatitis B virus can occur during the birthing process or during early childhood through close personal contact with blood of infected individuals (such as contact between open wounds or sharing contaminated toothbrushes). The brochure concludes that hepatitis B is one of the largest health threats for Asians. Thus, it is vital that all API be checked for hepatitis B and vaccinated if not previously exposed. Also, chronic carriers need to take control of their own health, learn about hepatitis B treatments available, and be regularly screened for liver cancer. The contact information for the Asian Liver Center is provided (650-72LIVER or http://liver.stanford.edu).
•
Galactosemia 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) 4HEP-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: Galactosemia is a rare hereditary disease leading not only to cirrhosis in infants, but more seriously, to early devastating illness if not diagnosed quickly. This disease is caused by elevated levels of galactose (a sugar in milk) in the blood, resulting from a deficiency of the liver enzyme required for its metabolism (breakdown). This brief fact sheet reviews galactosemia. The fact sheet covers the genetics of galactosemia, symptoms, diagnostic tests that may be used to confirm the condition, and treatment options (notably elimination of galactose from the diet). With early therapy, any liver damage which occurred in the first few days of life will nearly completely heal. The author concludes that galactosemia should be considered in any jaundiced infant because of the beneficial effects of early dietary restriction. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org).
•
Hepatitis B Treatment Information Source: Doylestown, PA: Hepatitis B Foundation. 2003. 2 p. Contact: Available from Hepatitis B Foundation. 700 East Butler Avenue, Doylestown, PA 18901-2697. (215) 489-4900 Fax: (215) 489-4920 Email:
[email protected]. Website: www.hepb.org. PRICE: Full-text available online at no charge.
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Summary: Hepatitis B (a type of liver inflammation caused by a virus) is the world's most common, serious liver infection. This fact sheet offers information about treatment options for hepatitis B virus (HBV) infections, noting that there are now promising drugs that can slow down liver damage caused by the virus. This means that there will be less damage done to the liver, and less change of developing serious liver disease later on. Written in a question and answer format, the fact sheet reviews currently approved treatments for HBV, patient selection considerations, clinical trials of new drug treatments, and how to obtain additional information. The reverse side of the fact sheet offers a full-page chart of compounds in development for the treatment of chronic HBV. For each compound, the chart lists the family and drug name, the mechanism by which it works, the company that makes the drug, the company's web site address, and the current status of that drug in the United States drug approval process. Drugs are categorized as interferons, nucleoside analogues, non-nucleoside anti-virals, noninterferon immune enhancers, and post-exposure or post-liver transplant treatment. Simple graphics illustrate the fact sheet. •
Hepatitis B Source: Cedar Grove, NJ: American Liver Foundation. 2000. 4 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: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Hepatitis B virus (HBV) can cause a serious form of hepatitis (inflammation of the liver). Chronic hepatitis B can lead to severe liver damage, cirrhosis (scarring of the liver), liver cancer, and death. This fact sheet reviews hepatitis B. Written in a question and answer format, the fact sheet covers the epidemiology of HBV, the vaccine available for preventing transmission of hepatitis B, risk factors for being infected with this virus, the symptoms of hepatitis B infection, the complications of hepatitis B, the problem of chronic hepatitis, a definition of carrier status and how to avoid transmitting the infection to others, diagnostic tests used to confirm hepatitis B, pregnancy and hepatitis B, and treatment options, notably interferon alfa 2b and lamivudine. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org).
•
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
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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). •
Understanding Hepatitis: A Glossary of Terms Source: Thousand Oaks, CA: Amgen, Inc. 1996. 20 p. Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. PRICE: Free to health professionals for distribution to patients. Summary: Hepatitis is a liver disease; chronic hepatitis infection can cause serious liver damage. This brochure provides a glossary of terms designed for the patient recently diagnosed with hepatitis. The author stresses that the more information and knowledge a patient can accumulate about his or her disease, the better participant he or she will be in health care decisions. The glossary defines terms briefly. Terms include the names of various diagnostic tests, the specialties of medicine that may be involved in the patient's care, words related to transmission of the virus and the types of viruses involved, symptoms, physiology, and treatment options.
•
Check Out the Facts About Hepatitis B and C (HBV and HCV) Source: Kenilworth, NJ: Schering Corporation. 1997. [2 p.]. Contact: Available from Schering Corporation. 2000 Galloping Hill Road, Kenilworth, NJ 07033. (800) 446-8766 or (908) 298-4000. Fax (908) 298-4490. Website: www.scheringplough.com. PRICE: Single copy free for patients; available to health professionals through local sales representatives. Summary: Hepatitis is an inflammation of the liver caused by a virus, drugs, or other factors. This fact sheet reviews basic information about hepatitis B virus (HBV) and hepatitis C virus (HCV). There are at present six types of viral hepatitis: A, B, C, D, E, and G. They differ in how they are transmitted as well as how long and how severely they affect the patient. Hepatitis A and E, milder forms, are spread through contaminated foods or water, while hepatitis B, C, and D (more serious forms) are spread through contact with human blood or by sexual activity. Hepatitis B and C have the greatest potential for long term liver damage. There is a vaccine to prevent hepatitis B, but not hepatitis C. Many people have few or no symptoms with HBV and HCV; blood tests may discover the infection. Liver function tests can then be performed to measure the severity of infection. Both hepatitis B and C are very common and can be either acute (short term, less than 6 months) or chronic (long term, more than 6 months) infections. The fact sheet stresses the important, varied roles of the liver, noting that a liver damaged by hepatitis cannot handle all these tasks very well. Hepatitis C can lead to permanent liver damage that may require a liver transplant. Almost one third of all liver transplants in the United States are needed because the patient had chronic hepatitis C. The fact sheet concludes by briefly reviewing prevention strategies for hepatitis B and C: never share needles or personal items that can hold blood (toothbrushes, razors), make sure that any tattooing or body piercing is done with sterile instruments, avoid multiple sex partners, and practice safer sex (use a latex condom).
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The fact sheet concludes with two toll free telephone hotlines where readers can get additional information: 800-GO-LIVER (465-4837) and 888-4HEP-ABC (443-7222). •
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.
•
Primary Biliary Cirrhosis Source: Cedar Grove, NJ: American Liver Foundation. 1992. 2 p. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (201) 256-2550 or (800) 223-0179. PRICE: Single copy free. Summary: Primary biliary cirrhosis (PBC) is a chronic liver disease that causes slow, progressive destruction of bile ducts in the liver. This fact sheet discusses PBC, covering its presentation, diagnosis, cause, prognosis, and treatment. Treatment includes diet therapy, drug therapy, and liver transplantation. A final section describes current research into the causes and development of the disease and drug therapy trials exploring the potential use of several medications to lessen the symptoms and control liver damage.
•
Understanding Your Liver: A Primer for Patients Source: Kenilworth, NJ: Schering Corporation. 1998. 14 p. Contact: Available from Schering Corporation. 2000 Galloping Hill Road, Kenilworth, NJ 07033. (800) 446-8766 or (908) 298-4000. Fax (908) 298-4490. Website: www.scheringplough.com. PRICE: Single copy free for patients; available to health professionals through local sales representatives. Summary: The liver performs many varied and complex functions, including cleaning and purifying the blood supply, breaking down certain chemical substances in the blood, storing sugars, fats and vitamins until they are needed, and manufacturing (synthesizes) substances such as complex proteins. This pocket sized booklet briefly reviews the anatomy and physiology of the liver. Topics include the location of the liver, functions of the liver, the physical exam, the architecture of the normal liver, the use of biopsy to determine whether there is liver damage, complications of hepatitis, and the symptoms of cirrhosis (liver scarring). Each topic includes a full color illustration and a brief description. If viral hepatitis infection occurs, it may resolve on its own or become chronic. However, many patients with chronic hepatitis often do not experience symptoms. Others complain of excessive fatigue, weakness, and a reduced capacity for
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exercise. Since liver damage may occur even in asymptomatic cases (no patient complaints), it is important to perform a biopsy and determine whether there is ongoing liver damage. The biopsy can indicate cellular necrosis (death of the liver cells), inflammation, and scarring (in which scar tissue begins to replace functioning liver cells). The booklet includes blank space for readers to record their notes or questions. •
Double Jeopardy: The HIV/HCV Co-Infection Handbook Source: New York, NY: Community Prescription Service. 1999. 36 p. Contact: Available from Community Prescription Service. 349 West 12th Street, New York, NY 10014. (800) 842-0502. PRICE: Single copy free. Summary: This booklet was written to help people with HIV and hepatitis C virus (HCV) coinfection (people with both diseases) understand their illness and treatment options. Readers are reassured that HCV is a very slow developing, long term chronic disease and that like HIV, it can be treated. Topics discussed are risk behaviors for both diseases, testing for HIV and HCV, negative test results, positive HIV or HCV test results, questions to ask the physician, HIV or AIDS, strategies for maintaining optimum liver health, liver damage, treatment options for hepatitis C, drug interactions, methadone interactions, interferon drug therapy for HCV, combination therapy for HCV, HCV drugs undergoing trials, alternative or complementary therapies, groups that help, concerns about hepatitis A and B, and substance abuse and cessation issues. The booklet includes a liver damage control chart, an HIV drug chart, and lists of resources, including organizations that offer local chapters and support groups. The information in the booklet is presented in bold typefaces and colors to set off different sections.
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Alpha 1-Antitrypsin Deficiency Liver Disease Source: Minneapolis, MN: Alpha 1 Association. 2000. [4 p.]. Contact: Available from Alpha 1 Association. 8120 Penn Avenue, South, Suite 549, Minneapolis, MN 55431-1326. (800) 521-3025 or (612) 703-9979. Fax (612) 703-9977. Email:
[email protected]. Website: www.alpha1.org. PRICE: $0.10 plus shipping and handling; bulk copies available. Summary: This brochure describes Alpha 1 antitrypsin deficiency (A1AD or Alpha 1), a genetic disorder that affects infants, children, and adults. It is the most common metabolic disorder that causes liver disease in infants and children; the disorder also causes cirrhosis and cancer of the liver in adults. The brochure reviews the functions of the liver, the causes of the deficiency, symptoms in children and adults, and treatment options. Alpha 1 antitrypsin (AAT) is a protein primarily manufactured in the liver and then released into the blood. The normal function of AAT is to protect body tissues from being damaged by neutrophil elastase, a protein found in white blood cells. The backup of abnormal AAT in the liver can cause liver damage. Symptoms of A1AD in children includes jaundice, low birth weight, mildly elevated liver enzymes, cholestasis, enlarged liver, abnormal bleeding, feeding difficulties, poor growth (or failure to thrive), and ascites (abnormal accumulation of fluids). In adults, the spectrum of liver disease associated with A1AD deficiency varies from mild to severe. Symptoms include chronic active hepatitis, cryptogenic cirrhosis (liver scarring of unknown cause), portal hypertension (high blood pressure in the portal vein of the liver), and hepatocellular carcinoma (liver cancer). Clinical care for all affected individuals largely involves supportive management for liver dysfunction and prevention of complications. For those who develop severe liver injury, liver transplantation is usually recommended.
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Proper nutrition is essential for everyone with A1AD. The brochure concludes with contact information for the Alpha 1 Association. 1 figure. 3 references. •
Hepatitis B: Understanding This Viral Infection Source: San Bruno, CA: StayWell Company. 2002. [2 p.]. Contact: StayWell Company: Krames Health and Safety Education. 780 Township Line Road, Yardley, PA 19067. (800) 333-3032. Fax (415) 244-4512. E-mail:
[email protected]. Website: www.staywell.com. PRICE: $ 20.95 for 50 copies; plus shipping and handling; bulk copies available. Order number 9781. Summary: This brochure describes hepatitis B, an inflammation of the liver caused by the hepatitis B virus (HBV). Hepatitis B infection can be acute or chronic. Symptoms of acute hepatitis B can include pain in the upper right abdomen, flulike symptoms, nausea and vomiting, diarrhea, and jaundice (yellowed skin or eyes, swelling of the abdomen, light stools, dark urine). People with chronic hepatitis B often have no symptoms. They may not know they have the virus until it causes liver disease years later. HBV is spread through blood and other body fluids; activities that can spread hepatitis B include sharing a needle with an infected person, having unprotected sex with an infected person, or using an infected person's eating utensils or personal care items. Hepatitis B is diagnosed through blood tests; other tests may diagnose associated liver damage. Patients who have chronic hepatitis B should avoid acetaminophen and other over the counter pain relievers, avoid alcohol, eat a balanced diet, keep appointments to monitor the liver's function, and get injections (of antiviral agents) if prescribed. One section outlines strategies for preventing the spread of hepatitis B. The brochure is illustrated with full color drawings. 7 figures.
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Porphyria Cutanea Tarda (PCT) Source: Houston, TX: American Porphyria Foundation. 199x. 6 p. Contact: Available from American Porphyria Foundation. P.O. Box 22712, Houston, TX 77227-2712. (713) 266-9617. Fax (713) 871-1788. Website: www.enterprise.net/apf/. PRICE: Single copy free to members only ($30.00 membership fee); online version available for $5.00 access fee. Summary: This brochure for health professionals and people with porphyria cutanea tarda (PCT) discusses the causes, symptoms, diagnosis, and treatment of this common form of porphyria. PCT is caused by a deficiency of uroporphyrinogen decarboxylase in the liver. Factors that could cause this deficiency include genetics, excess iron in the liver, excessive alcohol intake, hepatitis C, estrogens, drugs that increase porphyrin synthesis in the liver, HIV, and industrial chemicals. The most common symptoms are fragility, blistering, and crusting of the areas of the skin exposed to light; and mild or moderate liver damage is usually present as well. Diagnosis is based on marked increases in porphyrins in plasma and urine. The most widely used treatment is repeated phlebotomy, although low-dose chloroquine may also be used, particularly in patients who cannot tolerate phlebotomies. Because PCT is not progressive and is seldom disabling, the prognosis is usually excellent.
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Understanding Hepatitis C and Your Therapy Choices Source: Thousand Oaks, CA: Amgen. 1999. 11 p.
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Contact: Available from COMPASS Program, Amgen, Inc. 1 Amgen Center Drive, Professional Services, Mailstop 36-2-A, Thousand Oaks, CA 91362. (888) 508-8088. Website: www.infergen.com. PRICE: Single copy free. Summary: This brochure helps people with hepatitis C understand the treatment options available to them. Written in a question and answer format, the brochure first reviews the symptoms and complications of hepatitis C and how it is transmitted. Even though hepatitis C can cause serious liver damage, many infected people don't have any symptoms and don't know they are infected. Hepatitis C is bloodborne and can be transmitted by blood transfusion, shared needles, improperly sterilized tattooing and body piercing instruments, sharing of personal items, and multiple sexual contacts, and can be passed from an infected pregnant mother to her unborn child; some of these routes of transmission are quite rare. People with hepatitis C are generally categorized in three groups, based on their history of treatment for the disease: naive patients who have never before been treated for hepatitis C; relapsers are patients who have received hepatitis C therapy before but, although the therapy worked for awhile, it stopped working for them; or nonresponders, patients who tried hepatitis C therapy before but it never worked for them. The brochure outlines the types of approved therapies for hepatitis C, notably different types of interferon therapies and discusses the safety precautions that must be used by patients on interferon therapies. The brochure includes a blank form for patients to fill out which helps them to summarize their history with hepatitis and can clarify doctor patient communication. •
Hepatitis B and C Source: Santa Cruz, CA: Journeyworks Publishing. 1999. [2 p.]. Contact: Available from Journeyworks Publishing. P.O. Box 8466, Santa Cruz, CA 95061. (800) 775-1998. Fax (408) 423-8102. PRICE: Single copy free; bulk copies available. Summary: This brochure offers basic facts about hepatitis B and hepatitis C and ways to protect oneself from contracting either one. Hepatitis B and C can cause liver damage and lead to liver scarring, cancer, and sometimes death. Anyone who is sexually active or who uses needles needs to understand the risks of hepatitis B and C. Taking steps to protect oneself is important because hepatitis is much more contagious than HIV, and is difficult to treat. The brochure discusses how each type is transmitted and includes a brief section on hepatitis A. The brochure briefly reviews the symptoms of hepatitis infection, but emphasizes that people with hepatitis may not have any symptoms and could still be contagious. The brochure concludes with a list of recommendations for preventing hepatitis B and C: use a latex condom for vaginal, anal, or oral sex; do not share needles or other supplies for drugs, tattoos, body piercing, or acupuncture; do not share razors or toothbrushes; cover all cuts and open sores; get vaccinated for hepatitis B; and talk with sexual partners about safer sex. The brochure includes the toll free information lines from the American Liver Foundation (800-GO-LIVER) and the Centers for Disease Control and Prevention Hepatitis Information Line (888-443-7232). The brochure is illustrated with line drawings of youthful people representing a variety of ethnic groups.
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If You Have Hepatitis C 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, Bldg. 6, MS G-37, Atlanta, GA 30333. (800) 443-7232. Fax (404) 639-1538. Website: www.cdc.gov. PRICE: Single copy free.
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Summary: This brochure provides information for patients with hepatitis C, a liver disease spread by contact with the blood of an infected person. Written in question and answer format, the brochure helps readers better understand what the disease is, how they may have contracted it, and how they can avoid passing hepatitis C virus (HCV) to others. Many people with long term (chronic) hepatitis C have no symptoms and feel well, but they should still be under the care of a physician for long term monitoring. The brochure includes a special section for readers who are pregnant, stressing that infants can become infected at birth if their mothers have HCV. A drug called interferon is licensed for the treatment of people with long term hepatitis C; however, only about 2 of every 10 people who are treated get rid of the virus. The brochure concludes with a section reminding readers to take care of their livers by seeing a physician regularly, avoiding alcohol, telling their physician about all the medicines they are taking, and getting vaccinated against hepatitis A (for those people who already have liver damage from hepatitis C). The brochure includes the telephone number for the toll free Hepatitis Hotline (888 443 7232), as well as the Internet and the postal addresses. •
What is Hemochromatosis? Source: Cedar Grove, NJ: American Liver Foundation. 2001. [4 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: $0.75 for single copy; bulk orders available; plus shipping and handling. Summary: This brochure reviews hemochromatosis, an inherited condition that causes the body to absorb and store too much iron. The brochure answers common questions about hemochromatosis, covering the risk factors for the disease, the symptoms, diagnostic tests for iron overload, treatment options, the prognosis for people with hemochromatosis, the presence of anemia with iron overload, the role of alcohol in accelerating liver damage, the relationship between diet and iron overload, and liver transplantation in patients with hemochromatosis. The brochure concludes with a brief description of the American Liver Foundation (ALF), a nonprofit, national voluntary health organization dedicated to the prevention, treatment, and cure of hepatitis and other liver diseases through research, education, and advocacy.
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What is Viral Hepatitis? Source: Cedar Grove, NJ: American Liver Foundation. 2001. [6 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 brochure reviews viral hepatitis, an infection of the liver that affects people from all walks of life. The brochure first reviews the risks of viral hepatitis and how they can be avoided, including fecal and oral contamination, blood and body fluids, blood to blood contact, and potential risk factors. The brochure then summarizes the different types of hepatitis, including hepatitis C, hepatitis B, and hepatitis A, focusing on the symptoms, diagnosis, prevention, and therapy of each disease. The brochure emphasizes the need for screening tests, particularly for people who think they may have been exposed to infected blood. Vaccines for hepatitis A and B can provide
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long term protection from these diseases. The use of alcohol substantially increases the risk of serious liver damage in persons with chronic viral hepatitis, and thus should be avoided. The brochure concludes with a description of the work of the American Liver Foundation (ALF) and its contact information (www.liverfoundation.org). •
Does Your Patient Have Chronic Hepatitis B? Source: St. Paul, MN: Hepatitis B Coalition. 1997. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet answers common questions that health care providers may have about chronic hepatitis B virus (HBV) infection. Topics include how chronic HBV infection is diagnosed; the outcomes in a patient with chronic HBV infection, including the possibilities of liver cirrhosis and primary hepatocellular carcinoma (HCC, or liver cancer); the liver damage caused by HBV; the need for ongoing patient followup, even when test batteries indicate a lower infection rate; management of patients who are chronically infected with HBV; and the treatment modalities. Approximately 40 percent of suitable patients with chronic HBV with significant liver damage and ongoing viral replication benefit from treatment with interferon. Those who are most likely to respond to treatment for HBV are those who have evidence of liver damage and low HBV DNA levels. Because interferon may have significant risks and side effects associated with its use, treatment should be carried out by a gastroenterologist or hepatologist with experience in the antiviral treatment of chronic hepatitis. 1 table. (AA-M).
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Caring for Your Liver Source: Cedar Grove, NJ: Hepatitis Foundation International. 2001. 2 p. Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904-2901. (301) 622-4200. Fax (301) 622-4702. E-mail:
[email protected]. Website: www.hepatitisfoundation.org. PRICE: $2.00 for 5 copies; discounts available for bulk orders. Summary: This fact sheet from Hepatitis Foundation International presents basic information about the liver and its proper care. Topics covered include the physiology of the liver; anatomy and functions; the ability of the liver to regenerate; cirrhosis; the causes of liver cell damage; the role of alcohol in liver damage; liver problems from inhalants and aerosol fumes; risk factors and vaccination for hepatitis A; hepatitis B; hepatitis C; and hepatitis D. The fact sheet concludes that caring for one's liver means maintaining a healthy diet, exercising, getting lots of fresh air, and avoiding things that can cause liver damage.
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Questions Frequently Asked About Hepatitis B Source: St. Paul, MN: Immunization Action Coalition. 1996. 4 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104-6328. (612) 647-9009. Fax (651) 647-9131. E-mail:
[email protected]. Website: www.immunize.org. PRICE: Full-text available online at no charge; $1.00 for single copy. Item number: P4090. Summary: This fact sheet poses and answers questions frequently asked about hepatitis B, a viral infection that attacks the liver and can lead to severe illness, liver damage, and, in some cases, death. The fact sheet emphasizes that the best way to be protected from
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hepatitis B is to be vaccinated against the disease. Topics covered include risk factors, transmission, symptoms, recovery and prognosis considerations, how to know if one has ever been exposed to hepatitis B, hepatitis B carrier status, long-term effects of hepatitis B, why hepatitis B is so serious in pregnant women, prevention, the hepatitis B vaccine and how it is administered, how hepatitis B differs from hepatitis A and C, and where to get more information. The fact sheet concludes with a brief description of the Hepatitis B Coalition, a nonprofit organization that promotes hepatitis B vaccination for all infants, children, and adolescents. The fact sheet provides specific recommendations, especially for those readers who are hepatitis B carriers, for preventing transmission of the disease. 1 table. (AA-M). •
Methotrexate Source: American Academy of Family Physicians. 2003. 2 p. Contact: Available online from American Academy of Family Physicians. Website: http://familydoctor.org. Summary: This fact sheet provides patients with information on methotrexate (MTX), a drug that is used to treat rheumatoid arthritis, psoriasis, and other immune system disorders. Methotrexate is used to suppress an overactive immune system. Side effects include nausea, vomiting, loss of appetite, diarrhea, and mouth sores. MTX is taken orally or by injection. It is very important to take MTX as prescribed and to inform the doctor if a dose is missed. Patients should not drink alcohol while taking MTX as it can cause liver damage. Both women and men should use birth control while taking MTX. Women should not use MTX when breast feeding.
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Managing Side Effects : Living With ART Contact: Community AIDS Treatment Information Exchange, PO Box 1104, Toronto, (416) 203-7122, http://www.catie.ca. Summary: This fact sheet, for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses the side effects of antiretroviral therapy (ART). Although ART can help manage HIV, it often has mild to extremely severe side effects, and medications are not always the cause of symptoms. The fact sheet recommends that individuals consult their health care professionals to determine the causes. Causes of ART side effects and ways to cope with them such as using complementary, homeopathic therapies, or by varying ART dosage are discussed. Symptoms such as nausea, vomiting, diarrhea, rash, fever, flu-like symptoms, fatigue, and sleep problems and long-term side effects such as liver damage are also described.
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Cognex Source: Toronto, Ontario: Alzheimer Society of Canada. September 1993. [2 p.]. Contact: Alzheimer Society of Canada. 1320 Yonge Street, Suite 201, Toronto, Ontario M4T 1X2, CANADA. (416) 925-3552. PRICE: Free. Summary: This fact sheet, written in French, provides updated information on the drug Cognex (tacrine). It discusses what Cognex does, the role of acetylcholine in Alzheimer's disease (AD), what testing has been done to see if Cognex is helpful in AD, results of the tests, and incidence of side effects. The sheet explains that Cognex decreases the breakdown of acetylcholine, an element in the brain that helps transmission of information; that it may cause a brief 24-hour improvement in mental function in some patients; and that the drug may cause liver damage in some patients. The drug has
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approval for marketing in the United States, making it the first drug approved for the treatment of individuals with mild to moderate AD. Also available in English. (See: AZDC05647). •
Fifty Ways to Love Your Liver Source: Cedar Grove, NJ: American Liver Foundation. 200x. 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) 4 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: This health education brochure provides basic information about the liver, its role in general health, and how readers can prevent liver damage. The brochure features a liver-shaped cartoon character that provides the information, beginning with a description of the functions of the liver, including storage of iron, other minerals, and vitamin reserves; manufacture of bile to help digest food; detoxification of poisonous chemicals (including alcohol, medications, and other drugs); storage of energy; manufacture of proteins; detoxification of inhaled poisons; manufacture of clotting factors; and defense against infection. The brochure list 50 specific items of information or strategies for how to maintain a healthy liver, including the following: do not drink alcohol, do not use street drugs, do not smoke, take care of the liver to prevent illness, eat a good diet, get plenty of exercise, be aware that the liver is noncomplaining organ (it can be damaged without symptoms). Also know that there are higher incidences of hepatitis in certain ethnic groups and in people who have recently immigrated; transmission of hepatitis B can happen in all body fluids, including saliva; who should be tested for hepatitis B and C; what to do after receiving a positive test result for hepatitis; symptoms of liver trouble; the role of liver transplantation; the need for organ donors; and the activities of the American Liver Foundation (ALF). The brochure is illustrated with brightly colored graphics. One sidebar reviews the basic food groups and the nutritional role of each group. The brochure includes the hotline numbers and website for the ALF (www.liverfoundation.org ).
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Love Your Liver Workbook Source: Cedar Grove, NJ: American Liver Foundation. 1995. [18 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) 4 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: This health education coloring book provides basic information about the liver, its role in general health, and how young readers can prevent liver damage. The brochure features a liver-shaped cartoon character that provides the information, beginning with a description of the functions of the liver, including storage of iron, other minerals, and vitamin reserves; manufacture of bile to help digest food; detoxification of poisonous chemicals (including alcohol, medications, and other drugs); storage of energy; manufacture of proteins; detoxification of inhaled poisons; manufacture of clotting factors; and defense against infection. The brochure then offers pages that remind youngsters about how to maintain a healthy liver, including the following: do
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not drink alcohol, do not use street drugs, do not smoke, take care of the liver to prevent illness, eat a good diet, get plenty of exercise. •
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 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.
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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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Management of Chronic Hepatitis B in Children and Adults Source: St. Paul, MN: Hepatitis B Coalition. 1997. 12 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $5.00. Summary: This information packet contains six fact sheets addressing common concerns that health care providers may have about chronic hepatitis B virus (HBV) infection in children and adults. The six fact sheets are: Does Your Patient Have Chronic Hepatitis B?; Management of the HBsAg Positive Patient; Management of Chronic Hepatitis B in Adults; Management of Chronic Hepatitis B in Children and Adults; and What the Physician Can Do to Help the Child Who is a Hepatitis B Carrier. Topics include how chronic HBV infection is diagnosed; the outcomes in a patient with chronic infection, including the possibilities of liver cirrhosis and primary hepatocellular carcinoma (HCC, or liver cancer); the liver damage caused by HBV; the need for ongoing patient followup, even when test batteries indicate a lower infection rate; the management of patients who are chronically infected with HBV; the treatment modalities available; the natural history of HBV; risk factors for transmission; indications for testing of sexual and household contacts; and diagnostic testing and followup in children. 2 figures. 2 tables.
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Hepatitis C and HIV Contact: University of New Mexico School of Medicine, Infectious Diseases Division, New Mexico AIDS Education and Training Center, New Mexico AIDS InfoNet, PO Box 810, Arroyo Seco, NM, 87514-0810, (505) 776-8032, http://www.aidsinfonet.org. Summary: This information sheet discusses the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). Hepatitis C is a chronic viral liver disease that is transmitted through infected blood. Some people clear HCV from their bodies without treatment, but the majority of people infected with HCV develop chronic infection. Without treatment, serious liver damage can occur. The information sheet explains how hepatitis C is diagnosed, treated, and
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prevented. In addition, it discusses the impact of hepatitis C on individuals with HIV/AIDS. •
Enfermedades de Transmision Sexual: Hepatitis: Tipo A (Causada por el Virus de Hepatitis A) Contact: Minnesota Department of Health, Infectious Disease Epidemiology Prevention and Control Division, PO Box 9441, Minneapolis, MN, 55440-9441, (612) 676-5414, http://www.health.state.mn.us/divs/dpc/idepc.html. Summary: This information sheet presents an overview of hepatitis A, including information on signs and symptoms, routes of transmission, complications and consequences such as long-term liver damage, and prevention. It explains that there is no known treatment to shorten the course of acute hepatitis A infection. Sources for additional information are provided.
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Be Wise, Immunize!: Vaccinate on Time Source: Cleveland, OH: Learning Curve of Weingart Design. 199x. [2 p.]. Contact: Available from Learning Curve of Weingart Design. 4614 Prospect Avenue, Number 421, Cleveland, OH 44103-4314. (800) 795-9295. Fax (216) 881-7177. Website: www.learningcurve1.com. PRICE: $10.00 for a pack of 100; single copies are not available. Summary: This oversized bookmark lists the latest recommendations for pediatric immunizations from the Centers for Disease Control (CDC). The bookmark reminds parents that getting the shots (vaccinations) and getting all of them, is one of the most important things they can do for their babies. The front of the bookmark lists the age and recommended immunizations. The reverse side lists each of the immunizations and briefly notes what each one covers. Included are vaccines against hepatitis B, which causes liver damage; Hib (haemophilus influenzae b), which causes brain infection and brain damage; DTP or DTaP, which protects against diphtheria (serious breathing problems that can lead to paralysis and heart failure), pertussis (whooping cough), and tetanus (causes painful muscle spasms leading to lockjaw); polio (OPV), a disease that can paralyze arms and legs; MMR, measles, mumps, and rubella (rubella is German measles, a more serious form of measles that can lead to birth defects in babies); and varicella, or chicken pox. The schedule printed on the front of the bookmark is recommended by the American Academy of Pediatrics and the American Academy of Family Physicians.
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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
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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 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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Learn the Facts About Hepatitis C Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This pamphlet provides information about hepatitis C (HCV), a serious liver disease that is caused by a virus that is found in blood and other body fluids. The pamphlet discusses transmission, symptoms, and treatment of HCV. The symptoms are mild and flu-like and sometimes people have no symptoms. However a blood test can tell if an individual has HCV or any liver damage. The pamphlet includes suggestions to help persons with HCV live a healthy life and lists ways of preventing the disease by not sharing personal care items, needles, and syringes; explaining how to clean needles if using injecting drugs; and advises abstaining from sex or using a new, male latex condom if sexually active.
•
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.
•
Coping with Ulcers Source: Physician Assistant. p. 29. December 1999. Contact: Available from Springhouse Corporation. Physician Assistant, P.O. Box 908, Springhouse, PA 19477. (215) 646-8700. Fax (215) 646-4399. Summary: This patient handout reviews peptic ulcer disease (PUD), commonly referred to as ulcers, and defined as sores or craters in the lining of the stomach (gastric ulcers) or in the first part of the small intestine called the duodenum (duodenal ulcers). The handout offers information about the causes of ulcers, risk factors that make it more likely to get ulcers, treatment options, and the possible complications of ulcers. Gastric ulcers are caused when the lining of the stomach is injured. Risk factors for gastric ulcers include regular use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), excess amounts of bile in the stomach, Helicobacter pylori infection, type O blood, and uncommon tumors called gastrinomas (usually found in the pancreas). Duodenal ulcers develop when an overproduction of enzymes, such as stomach acid, bile or other enzymes, overwhelms the layer of mucus protecting the surface of the duodenum. Risk
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factors for duodenal ulcers include regular use of aspirin or NSAIDs, smoking, chronic kidney failure, liver damage from alcohol, infection with Helicobacter pylori bacteria, and type O blood. Lifestyle modifications, including smoking cessation, avoidance of NSAIDs, and weight loss, are usually the first line of defense against ulcers. Complications of untreated ulcers can include significant blood loss, intestinal blockage, perforation of the stomach lining or small intestine with spillage of acid, bile, and other substances into the abdominal cavity, and stomach cancer. The handout concludes with the contact information for two resource organizations: American Gastroenterology Association and the International Foundation for Functional Gastrointestinal Disorders. •
Hagase la Prueba de la Hepatitis C: Debe hacerse la prueba de la Hepatitis C si se le ha notificado que ha recibido sangre posiblemente infectada por el virus hepatitis C (VHC) o si usted ha recibido sangre Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This Spanish-language pamphlet discusses who should be tested for hepatitis C and the effects, treatment, transmission, and prevention of hepatitis C. Persons should be tested if they were notified that they received blood that possibly contained hepatitis C virus (HCV) or if they received blood before July 1992. Persons may have received this blood before tests to identify blood donors with hepatitis C were available or when tests were less precise than they are now. Hepatitis C is a liver disease caused by infection with HCV, which is found in the blood of persons who have this disease. If persons test positive for hepatitis C, they will need to see a doctor to determine if they have liver disease and how severe it is, to determine if they should be treated for the liver disease, to learn how they can protect their livers from further harm, and to learn how they can prevent spreading HCV to others. Persons should not donate blood as a means of being tested. Whether persons feel sick or not, they should have a blood test for hepatitis C. 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. Antiviral medicines are approved for the treatment of persons with chronic hepatitis C. Treatment is effective in about 2-3 out of every 10 persons treated. Others at risk of getting hepatitis C are persons who have ever injected street drugs, healthcare workers exposed to blood in the workplace, and babies born to infected mothers. HCV also can be spread by sex, but this does not occur very often. 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. Sexual practices involving one steady partner do not need to change, and persons with HCV do not need to avoid pregnancy or breast feeding. 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.
•
Hepatitis Information You Need to Know: The Impact of Viral Hepatitis in Our Community Source: New York, NY: American Liver Foundation. 2000. [4 p.]. Contact: Available from American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038-4810. (800) 465-4837. Fax (212) 483-8179. E-mail:
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[email protected]. Website: www.liverfoundation.org. PRICE: $.75 for single copy; discounts available for bulk orders. Summary: Viral hepatitis is an infection of the liver that affects people from all walks of life regardless of age, race, gender, or sexual orientation. This brochure describes the different types of viral hepatitis and provides information about avoiding the risk factors that enable transmission of hepatitis. Hepatitis A infection can cause an acute, flu like illness with yellowing of the skin (jaundice), nausea and vomiting, fatigue, loss of appetite, abdominal pain, or diarrhea. Hepatitis B infection can causes symptoms similar to hepatitis A; in approximately 5 percent of cases, it becomes chronic and can result in cirrhosis (liver scarring). Hepatitis C infection can result in up to 85 percent of cases becoming chronic, and often causes no symptoms until liver damage has occurred many years after infection. Risk factors for each type of hepatitis are outlines, with a special section discussing the emerging epidemic of hepatitis C infection. The brochure then encourages readers to consider getting tested for hepatitis; this section briefly describes the treatment options for the main types of hepatitis. Adoption of a healthy lifestyle with a good diet, plenty of rest, and stress reduction can improve one's health and well being. Studies show that the use of alcohol substantially increases the risk of serious liver damage in persons with chronic viral hepatitis, and thus should be avoided. The brochure then discusses a viral hepatitis education campaign, the Digestive Health Initiative (DHI), which is educating consumers, patients, physicians, policy makers, and other healthcare professionals about hepatitis. The brochure concludes with a list of sources of information and support for people affected by hepatitis. 1 table. 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 damage. 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 damage. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with liver damage. 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 damage. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “liver damage” (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 damage”. 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 damage” (or synonyms) into the “For
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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 damage” (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.22
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
22
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)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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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
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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
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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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 DAMAGE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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 myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH]
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Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] 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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adduction: The rotation of an eye toward the midline (nasally). [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
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]
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Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [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] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. [NIH]
Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU]
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Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH] Alpha 1-Antitrypsin Deficiency: A disease caused by single gene defects. [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-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] 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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [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] 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,
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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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] 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] Androgenic: Producing masculine characteristics. [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] 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] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] 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]
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Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anthelmintic: An agent that is destructive to worms. [EU] 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] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] 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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and
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febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] 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; 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] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] 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] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]
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Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] 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] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] 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 Translocation: The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. [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
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coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] 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 Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]
Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to
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fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopterin: A natural product that has been considered as a growth factor for some insects. [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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [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] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH]
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Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] 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] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [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
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many enzymatic processes. [NIH] Calcium blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calendula: Genus of annuals in the family Asteraceae that contains carotenoids, essential oils (oils, volatile), flavonoids, mucilage, saponins, and sterols. It is used both topically and internally. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbimazole: An imidazole antithyroid agent. Carbimazole is metabolized to methimazole, which is responsible for the antithyroid activity. [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] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [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]
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Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalyse: To speed up a chemical reaction. [EU] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is
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being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] 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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [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] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH]
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Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Choleretic: A choleretic agent. [EU] Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter. [NIH] 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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] 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] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical 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]
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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] Cloxacillin: A semi-synthetic antibiotic that is a chlorinated derivative of oxacillin. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Color blindness: A form of defective color vision requiring only two primary colors, mixed
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in various proportions, to match all other colors. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] 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 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] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] 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]
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Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] 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] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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 study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type
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of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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 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] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH]
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Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystamine: A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. [NIH] Cysteamine: A radiation-protective agent that oxidizes in air to form cystamine. It can be given intravenously or orally to treat radiation sickness. The bitartrate has been used for the oral treatment of nephropathic cystinosis. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] 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] Cytotoxic: Cell-killing. [NIH]
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Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [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] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defibrotide: A drug under study for the prevention of veno-occlusive disease, a rare complication of high-dose chemotherapy and stem cell transplantation in which small veins in the liver become blocked. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), 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] 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] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
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Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] 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] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] 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] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimercaprol: 2,3-Dimercapto-1-propanol. An anti-gas warfare agent that is effective against Lewisite (dichloro(2-chlorovinyl)arsine). It acts as a chelating agent and is used in the treatment of arsenic, gold, and other heavy metal poisoning. [NIH]
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Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dimethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents. [NIH]
Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [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] 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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]
Duodenum: The first part of the small intestine. [NIH] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] 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 produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] 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] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU]
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Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [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] Enhancer: Transcriptional element in the virus genome. [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 Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] 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]
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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] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [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] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [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] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU]
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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] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members. [NIH]
Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] 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] Fatty Liver, Alcoholic: Fatty liver in alcoholics. It is potentially reversible and may be associated with alcoholic hepatitis or cirrhosis. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Ferrochelatase: An enzyme widely distributed in cells and tissues. It is located in the inner mitochondrial membrane and catalyzes the formation of heme from protoporphyrin IX and ferrous ions during the terminal step in the heme biosynthetic pathway. EC 4.99.1.1. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH]
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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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorosis: Discoloration of the tooth enamel due to fluorine. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [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] 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] Fungistatic: Inhibiting the growth of fungi. [EU] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd,
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atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] 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] Gamma-Glutamyltransferase: An enzyme that catalyzes reversibly the transfer of a glutamyl group from a glutamyl-peptide and an amino acid to a peptide and a glutamylamino acid. EC 2.3.2.2. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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.,
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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 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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] 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] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]
Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [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]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their
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molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] 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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Haemophilus influenzae: A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. [NIH]
Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal
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condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] 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] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [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 Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body 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] 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] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] 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]
Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is
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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 B: Hepatitis caused by hepatitis B virus. It may be transmitted by transfusion of contaminated blood or blood products. [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 E: An acute form of hepatitis caused by a virus serologically distinct from the agents of hepatitis A, B, and C. Hepatitis E is associated with fecally-contaminated water, is enterically transmitted, and is commonly found in tropical or subtropical countries. [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] 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] Hepatologist: A doctor who specializes in liver diseases. [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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of
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bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [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] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hyaluronidase: An enzyme that splits hyaluronic acid and thus lowers the viscosity of the acid and facilitates the spreading of fluids through tissues either advantageously or disadvantageously. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [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
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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] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] 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] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypervascular: Having a large number of blood vessels. [NIH] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [NIH] Hypophyseal: Hypophysial. [EU] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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]
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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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [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] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [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 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] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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
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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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [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] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH]
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Insomnia: Difficulty in going to sleep or getting enough sleep. [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] 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] 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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin
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or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] 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]
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] 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
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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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lactulose: A mild laxative. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [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]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] 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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [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]
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Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid 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] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [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] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [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 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 Mitochondria: Yellow discoloration of the liver due to fatty degeneration of liver parenchymal cells; the cause may be chemical poisoning. [NIH] Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobule: A small lobe or subdivision of a lobe. [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]
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Localized: Cancer which has not metastasized yet. [NIH] Lockjaw: Inability to open the mouth due to tonic contracture of the muscles of the jaw. [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 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] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] 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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] 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]
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Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malathion: A wide spectrum aliphatic organophosphate insecticide widely used for both domestic and commercial agricultural purposes. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Mefloquine: A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against Plasmodium falciparum with very few side effects. [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 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 Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [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]
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Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] 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] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] 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] Methimazole: A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. Before its alphaadrenergic actions became clear, methyldopa was thought to act by inhibiting decarboxylation of DOPA leading to depletion of norepinephrine or by conversion to and release as the false transmitter alpha-methylnorepinephrine. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [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] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU]
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Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [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] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles
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are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopathy: Any disease of a muscle. [EU] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU]
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Nasal Mucosa: The mucous membrane lining the nasal cavity. [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] 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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] 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] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH]
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Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrofurantoin: A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and longterm suppression. [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] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by
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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] Nucleoprotein: Chromosomes consist largely of nuclei acids and proteins, joined here as complexes called nucleoproteins. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [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] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] 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] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxacillin: An antibiotic similar to flucloxacillin used in resistant staphylococci infections.
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[NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxyquinoline: An antiseptic with mild fungistatic, bacteriostatic, anthelmintic, and amebicidal action. It is also used as a reagent and metal chelator, as a carrier for radioindium for diagnostic purposes, and its halogenated derivatives are used in addition as topical anti-infective agents and oral antiamebics. [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] 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] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] 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] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other
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route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] 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 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] Pelvis: The lower part of the abdomen, located between the hip bones. [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] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] 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]
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Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [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] Perivascular: Situated around a vessel. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, 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.
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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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [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] Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [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] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized
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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 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] 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] 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] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyvinyl Chloride: A polyvinyl resin used extensively in the manufacture of plastics, including medical devices, tubing, and other packaging. It is also used as a rubber substitute. [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]
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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] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [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 Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portography: Examination of the portal circulation by the use of X-ray films after injection of radiopaque material. [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] 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] Potentiate: 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] 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] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH]
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Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]
Prenatal: Existing or occurring before birth, with reference to the fetus. [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 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] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [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] 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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] 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
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configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [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]
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]
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Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] 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 Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] 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]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] 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
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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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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
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remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [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] 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 Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
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] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] 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]
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Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribonuclease: RNA-digesting enzyme. [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] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [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] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] 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]
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Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [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] Schistosome: Dermatitis caused by the snail parasite, Schistosoma cercariae. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH]
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Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Siderosis: The deposition of iron in a tissue. In the eye, the iron may be deposited in the stroma adjacent to the Descemet's membrane. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet
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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] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasmodic: Of the nature of a spasm. [EU]
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Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Steatosis: Fatty degeneration. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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
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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] 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 suburban and rural areas, and tend to be grossly impure and may cause unexpected toxicity. [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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] 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]
Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU]
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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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] 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] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
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Thioacetamide: A crystalline compound used as a laboratory reagent in place of hydrogen sulfide. It is a potent hepatocarcinogen. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by 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 Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of
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restoring normal tone to tissue. [EU] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] 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] 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] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [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]
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Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [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] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] 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] Triolein: (Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester. [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] 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] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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]
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Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Unresectable: Unable to be surgically removed. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] 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] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [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] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in
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which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Varicella: Chicken pox. [EU] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: 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]
Dictionary 253
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] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the
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cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
255
INDEX A Abdomen, 114, 130, 158, 181, 191, 205, 218, 221, 231, 245, 246, 248 Abdominal, 62, 122, 165, 169, 170, 181, 221, 230, 251 Abdominal Pain, 122, 165, 170, 181, 251 Abortion, 118, 181 Abscess, 126, 181 Acatalasia, 181, 193 Acceptor, 181, 221, 230, 249 Acetaminophen, 29, 44, 69, 75, 90, 91, 92, 93, 94, 96, 140, 158, 181, 208 Acetylcholine, 162, 181, 195, 228 Actin, 7, 181, 226 Acute leukemia, 51, 181 Acute lymphoblastic leukemia, 56, 181 Acute lymphocytic leukemia, 181 Acute myelogenous leukemia, 181, 182 Acute myeloid leukemia, 10, 181, 182 Acute nonlymphocytic leukemia, 181, 182 Acute renal, 67, 182 Acyl, 182, 223 Adaptability, 182, 193 Adduct, 20, 21, 29, 182 Adduction, 22, 182 Adenocarcinoma, 182, 213 Adenovirus, 24, 182 Adipose Tissue, 27, 182 Adjuvant, 21, 182 Adrenal Cortex, 182, 199 Adrenal Glands, 182, 185 Adrenergic, 182, 203, 206, 224 Adverse Effect, 26, 136, 182, 219, 233, 243 Aerobic, 182, 225, 230 Aerobic Metabolism, 182, 230 Aerobic Respiration, 182, 230 Aerosol, 161, 182 Affinity, 61, 182, 183, 244 Age-Adjusted, 14, 183 Agonist, 183, 203, 224 Agranulocytosis, 41, 42, 183 Alanine, 15, 26, 27, 69, 183 Alanine Transaminase, 15, 27, 183 Albumin, 14, 15, 183, 234 Alcohol Dehydrogenase, 5, 42, 73, 183 Aldehydes, 21, 22, 183 Algorithms, 183, 190 Alimentary, 183, 230, 231
Alkaline, 27, 183, 184, 191 Alkaline Phosphatase, 27, 183 Alkaloid, 183, 196, 225, 230 Alkylating Agents, 183, 201 Alleles, 13, 183 Allergen, 183, 202 Allogeneic, 184, 232 Allograft, 184, 227 Alopecia, 184, 200 Alpha 1-Antitrypsin, 40, 81, 157, 184 Alpha 1-Antitrypsin Deficiency, 81, 157, 184 Alpha Particles, 184, 238 Alpha-fetoprotein, 41, 184, 208 Alternative medicine, 34, 135, 184 Ameliorating, 111, 117, 184 Amino Acid Sequence, 22, 184, 186, 206, 236 Amino Acid Substitution, 111, 117, 184 Amino-terminal, 184, 236 Ammonia, 15, 130, 184, 214, 251 Amphetamines, 184, 196 Amplification, 32, 184 Ampulla, 185, 195 Amyloidosis, 123, 124, 185 Anabolic, 185, 206 Anaerobic, 185, 211 Anaesthesia, 39, 53, 59, 72, 185, 217 Anal, 159, 185, 222 Analgesic, 181, 185, 196, 215, 225, 229 Analog, 185, 220 Anaphylatoxins, 185, 197 Anatomical, 185, 194, 202, 204, 216 Androgenic, 185, 201 Androgens, 72, 182, 185, 199 Anemia, 64, 160, 185, 189, 247 Anesthesia, 185 Aneurysm, 185, 252 Angina, 110, 185 Angina Pectoris, 110, 185 Anginal, 185, 228 Animal model, 8, 10, 14, 34, 35, 185 Anions, 183, 186, 219 Anthelmintic, 186, 230 Antibacterial, 186, 219, 245 Antibiotic, 186, 196, 206, 229, 245 Antibodies, 11, 21, 42, 186, 212, 215, 222, 234, 243
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Antibody, 11, 21, 33, 38, 39, 55, 57, 77, 131, 182, 186, 197, 206, 212, 214, 215, 216, 217, 223, 225, 239, 245 Anticoagulant, 186, 237, 253 Anticonvulsant, 61, 186, 232, 252 Antidepressant, 186, 252 Antigen-Antibody Complex, 186, 197 Antigen-presenting cell, 186, 201 Antihypertensive, 186, 224 Anti-infective, 186, 214, 219, 228, 230 Anti-Infective Agents, 186, 230 Anti-inflammatory, 181, 186, 188, 199, 202, 210, 215, 241 Anti-Inflammatory Agents, 186, 188, 199 Antimetabolite, 186, 224, 240 Antineoplastic, 183, 186, 199, 200, 224, 244 Antioxidant, 9, 29, 33, 77, 85, 90, 92, 93, 108, 114, 186, 188, 230, 244 Antipyretic, 181, 186 Antiseptic, 187, 230 Antispasmodic, 187, 229 Antitussive, 187, 229 Antiviral, 7, 32, 72, 127, 136, 158, 161, 169, 187, 218, 231, 240 Antiviral Agents, 127, 158, 187 Anuria, 187, 219 Anus, 185, 187, 191, 196 Anxiety, 85, 187, 219 Apolipoproteins, 69, 187, 221 Apoptosis, 7, 8, 15, 18, 23, 31, 38, 48, 187, 193 Applicability, 24, 187 Aqueous, 90, 187, 189, 200, 214 Arachidonic Acid, 187, 236 Arginine, 7, 185, 187, 228, 250 Arrhythmia, 187, 252 Arterial, 19, 47, 52, 110, 187, 195, 199, 215, 237, 247 Arteries, 187, 190, 199, 222, 224, 226 Arteriography, 47, 187 Arteriolar, 187, 191, 207 Arteriosclerosis, 187, 215, 226 Artery, 185, 187, 199, 204, 226, 231, 238, 240, 241 Ascorbic Acid, 108, 188, 214 Asparaginase, 66, 188 Aspartate, 15, 26, 43, 188 Aspiration, 188, 208 Aspirin, 96, 168, 188 Assay, 14, 27, 31, 73, 115, 188, 216 Asymptomatic, 109, 126, 157, 181, 188, 189, 213, 230
Atrial, 188, 199, 253 Atrial Fibrillation, 188, 253 Atrophy, 188, 221 Attenuation, 10, 188 Autodigestion, 188, 230 Autoimmune disease, 16, 109, 110, 112, 118, 188 Autoimmune Hepatitis, 109, 110, 125, 188 Autoimmunity, 41, 42, 188 Autologous, 124, 188, 232 Autonomic, 181, 188, 228, 232 B Bacteria, 169, 182, 186, 188, 189, 198, 200, 201, 204, 205, 207, 209, 211, 224, 239, 243, 245, 249, 251, 252 Bacterial Translocation, 75, 188 Bactericidal, 188, 206 Bacteriophage, 188, 249 Bacteriostatic, 189, 206, 230 Bacterium, 189, 198 Base, 189, 200, 201, 219, 220, 247, 251 Base Sequence, 189, 200 Basophils, 183, 189, 211, 220 Benign, 43, 123, 189, 201, 212, 227, 239, 241 Beta-Thalassemia, 43, 189 Bile Acids, 23, 189, 245, 247 Bile Acids and Salts, 189 Bile duct, 43, 124, 156, 189, 209, 236 Bile Pigments, 189, 219 Biliary, 45, 75, 91, 94, 110, 122, 123, 126, 156, 189, 195, 197, 230 Biliary Atresia, 75, 189 Biliary Tract, 189, 230 Bilirubin, 15, 124, 183, 189, 209, 215 Bioavailability, 30, 189 Biochemical, 23, 36, 70, 74, 114, 115, 126, 183, 184, 186, 189, 211, 219, 220, 243 Biological response modifier, 189, 190, 218 Biological therapy, 189, 211 Biomarkers, 15, 190 Biopsy, 13, 45, 113, 156, 190 Biopterin, 190, 227 Biotechnology, 36, 37, 38, 135, 147, 190 Biotransformation, 35, 190 Biotypes, 190, 211 Biphasic, 30, 190 Bladder, 136, 190, 227, 237, 251 Blood Coagulation, 117, 190, 191, 248 Blood Coagulation Factors, 190 Blood pressure, 157, 186, 190, 207, 215, 225, 228, 235, 244 Blood transfusion, 155, 159, 164, 167, 190
257
Blood vessel, 190, 191, 192, 194, 199, 204, 205, 207, 215, 219, 221, 222, 231, 233, 244, 246, 248, 252 Blood-Brain Barrier, 190, 247 Body Composition, 26, 28, 190 Body Fluids, 158, 160, 163, 164, 168, 190, 204, 208, 227, 229, 244, 250 Bone Marrow, 13, 42, 45, 136, 181, 182, 191, 200, 209, 216, 222, 232, 245 Bone Marrow Transplantation, 42, 191 Bone scan, 191, 242 Bowel, 96, 185, 191, 202, 217, 218, 220, 227, 251 Bowel Movement, 191, 202 Brachytherapy, 191, 218, 239 Bradykinin, 191, 228, 234 Branch, 177, 191, 222, 231, 238, 245, 247 Breakdown, 6, 153, 162, 191, 202, 209 Bronchiseptica, 191, 232 Buccal, 191, 222 C Cachexia, 33, 191 Calcitonin, 20, 191 Calcitonin Gene-Related Peptide, 20, 191 Calcium, 23, 76, 108, 110, 191, 192, 197, 207, 217, 226, 228, 230, 237, 243, 252 Calcium blocker, 110, 192 Calcium channel blocker, 192, 252 Calendula, 84, 192 Calmodulin, 192, 217 Calpain, 24, 192 Capsules, 28, 192 Carbimazole, 43, 109, 192 Carbohydrate, 192, 199, 210, 211, 234 Carbon Dioxide, 192, 200, 201, 240 Carboxy, 118, 192 Carcinogen, 116, 182, 192 Carcinogenic, 183, 192, 203, 217, 236, 245 Carcinoma, 192 Cardiac, 27, 188, 192, 199, 206, 210, 226, 245 Carnitine, 15, 68, 192 Carotene, 85, 86, 97, 101, 192 Carotenoids, 192 Carrier Proteins, 21, 117, 192, 234 Carrier State, 126, 192 Caspase, 24, 193 Catalase, 5, 181, 193 Catalyse, 193, 249 Cathode, 193 Cations, 9, 193, 219 Causal, 124, 193, 247
Cause of Death, 31, 193 Cell, 7, 8, 9, 10, 11, 15, 16, 18, 21, 23, 24, 25, 29, 30, 31, 33, 34, 35, 48, 57, 65, 66, 70, 85, 103, 114, 116, 118, 123, 124, 161, 181, 182, 183, 184, 185, 186, 187, 188, 190, 192, 193, 194, 195, 197, 198, 200, 201, 202, 205, 206, 207, 209, 210, 211, 213, 216, 217, 218, 220, 225, 226, 227, 228, 229, 230, 232, 233, 234, 237, 239, 240, 243, 244, 248, 249, 250, 252, 253 Cell Death, 23, 31, 33, 36, 118, 187, 193, 210 Cell Differentiation, 19, 193, 243 Cell Division, 10, 188, 193, 211, 225, 234 Cell membrane, 192, 193, 202, 209, 217, 233, 244 Cell motility, 193, 213 Cell proliferation, 11, 31, 33, 116, 187, 193, 243 Cell Respiration, 182, 193, 225, 230, 240 Cell Survival, 34, 193, 211 Cell Transplantation, 103, 193 Cellulose, 193, 234 Central Nervous System, 15, 181, 183, 184, 193, 196, 209, 212, 225, 229, 243, 247 Centrifugation, 193, 224 Ceramide, 23, 24, 26, 193 Cerebellar, 194, 250 Cerebellar Diseases, 194, 250 Ceroid, 194, 221 Cervical, 194, 241 Cervix, 181, 194 Character, 163, 185, 194, 201 Chelation, 78, 194 Chelation Therapy, 78, 194 Chemoembolization, 59, 194 Chemokines, 32, 194 Chemotactic Factors, 194, 197 Chemotherapy, 121, 194, 201 Chenodeoxycholic Acid, 45, 194, 251 Chin, 194, 224 Chlorophyll, 194, 200 Chloroplasts, 194, 200 Chloroquine, 158, 195 Cholecystectomy, 52, 195 Choleretic, 194, 195, 251 Cholestanol, 56, 195 Cholestasis, 23, 112, 157, 195 Cholesterol, 19, 23, 26, 27, 38, 57, 59, 96, 117, 189, 195, 209, 215, 221, 222, 223, 242, 245 Cholesterol Esters, 195, 221 Choline, 44, 195
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Choroid, 195, 240 Chromatin, 5, 187, 195, 205 Chromosomal, 184, 195, 241 Chromosome, 195, 198, 211, 221, 241, 250, 251 Chronic Disease, 5, 157, 191, 195, 220 Chylomicrons, 195, 221 Cirrhosis, 4, 6, 7, 8, 12, 16, 58, 91, 109, 110, 112, 113, 123, 125, 126, 127, 129, 136, 152, 153, 154, 156, 157, 161, 164, 165, 166, 167, 168, 170, 195, 207, 212, 235, 236, 252 CIS, 5, 195, 216 Citrus, 188, 195 Clear cell carcinoma, 195, 202 Clinical Medicine, 80, 115, 195, 235 Clinical trial, 5, 11, 44, 103, 104, 147, 154, 195, 198, 200, 203, 231, 237, 239 Clone, 5, 195 Cloning, 190, 196 Cloxacillin, 60, 196 Coagulation, 39, 47, 48, 49, 50, 190, 196, 212, 234, 248, 253 Coca, 196 Cocaine, 78, 196 Codeine, 140, 196, 229 Codon, 65, 196 Coenzyme, 188, 196, 220 Cofactor, 6, 196, 237, 248 Colchicine, 196, 250 Colitis, 96, 196 Collagen, 13, 16, 70, 76, 184, 196, 208, 234, 236 Collapse, 191, 196 Colloidal, 183, 196 Colon, 196, 217, 220, 251 Color blindness, 71, 196 Combination chemotherapy, 10, 197 Combination Therapy, 50, 157, 197 Common Bile Duct, 52, 197, 200 Complement, 36, 44, 55, 114, 185, 197, 223, 234 Complementary and alternative medicine, 89, 90, 101, 197 Complementary medicine, 90, 197 Complete remission, 197, 240 Computational Biology, 147, 197 Computed tomography, 197, 242 Conception, 181, 198, 208, 245 Condoms, 167, 168, 169, 198 Conjugated, 189, 194, 198, 200, 226 Conjugation, 111, 118, 190, 198
Conjunctiva, 198, 217 Connective Tissue, 188, 191, 196, 198, 202, 208, 209, 222, 240, 247 Connexins, 198, 209 Consciousness, 185, 198, 201, 203, 212, 238 Constipation, 122, 198 Constriction, 198, 219, 241 Consumption, 5, 8, 14, 16, 17, 18, 20, 21, 37, 40, 46, 123, 125, 198, 229, 230 Contamination, 116, 160, 198, 213 Contracture, 198, 222 Contraindications, ii, 198 Control group, 4, 28, 198 Controlled study, 49, 198 Conventional therapy, 136, 198, 199 Conventional treatment, 198 Convulsions, 186, 199 Cor, 199 Coronary, 110, 185, 199, 224, 226 Coronary Circulation, 185, 199 Coronary Thrombosis, 199, 224, 226 Corticosteroid, 21, 199 Cortisol, 183, 199 Cortisone, 199, 202 Creatine, 27, 59, 87, 199 Creatine Kinase, 27, 59, 199 Creatinine, 199, 200, 219, 251 Curative, 200, 247 Cutaneous, 200, 222, 233 Cyanobacteria, 37, 200 Cyclic, 31, 192, 200, 211, 228, 235, 237 Cyclophosphamide, 136, 200 Cyclosporine, 200, 216 Cystamine, 200 Cysteamine, 70, 200 Cystic Duct, 197, 200 Cytochrome, 5, 9, 70, 200 Cytokine, 11, 18, 26, 30, 200, 244 Cytoplasm, 24, 187, 189, 193, 200, 205, 217, 226 Cytotoxic, 21, 72, 200, 239, 243 Cytotoxicity, 4, 21, 34, 57, 201 D Dacarbazine, 46, 68, 201 Dairy Products, 201, 242 Danazol, 46, 58, 201 Data Collection, 201, 208 Deamination, 115, 201, 251 Decarboxylation, 201, 213, 224, 251 Decision Making, 73, 201 Defibrotide, 103, 201 Degenerative, 109, 201, 213
259
Delavirdine, 201, 228 Deletion, 13, 187, 201 Dementia, 131, 201 Dendrites, 201, 227 Dendritic, 18, 201, 223 Dendritic cell, 18, 201 Density, 38, 59, 193, 201, 221, 229 Dental Caries, 201, 208 Depolarization, 9, 202, 243 Depressive Disorder, 202, 221 Dermis, 202, 240 DES, 22, 185, 202 Desensitization, 9, 202 Detoxification, 15, 17, 29, 115, 125, 131, 163, 202 Dexamethasone, 49, 202 Diagnostic procedure, 4, 107, 135, 202, 233 Dialyzer, 202, 212 Diarrhea, 122, 158, 162, 170, 202 Diastolic, 202, 215 Dietitian, 129, 202 Digestion, 117, 129, 183, 189, 191, 202, 218, 221, 231, 246, 252 Digestive system, 104, 122, 202, 209 Digestive tract, 202, 244 Dilatation, 181, 185, 202, 252 Dilatation, Pathologic, 202, 252 Dilation, 191, 202, 252 Dilution, 42, 202 Dimercaprol, 70, 202 Dimethyl, 68, 203 Dimethylnitrosamine, 94, 95, 203 Diphtheria, 10, 166, 203 Diphtheria Toxin, 10, 203 Diploid, 203, 234 Direct, iii, 5, 15, 18, 21, 23, 24, 34, 110, 139, 195, 203, 230, 239 Disease Progression, 7, 15, 17, 18, 203, 252 Disinfectant, 203, 206 Dissociation, 182, 203, 219 Distal, 5, 203, 238 Dopamine, 196, 203, 228, 232 Double-blind, 28, 49, 203 Drug Approval, 124, 139, 154, 203 Drug Interactions, 64, 131, 141, 157, 203 Drug Tolerance, 204, 248 Duct, 152, 185, 197, 204, 206, 241, 245 Duodenal Ulcer, 168, 204 Duodenum, 168, 189, 204, 231, 246 Dynein, 37, 204 E Ectopic, 24, 204
Edema, 204, 226, 235, 251 Effector, 32, 181, 197, 204 Efficacy, 15, 36, 49, 62, 110, 204 Ejaculation, 204, 242 Elastin, 196, 204 Electrocoagulation, 196, 204 Electrolysis, 186, 193, 204 Electrolyte, 199, 204, 208, 220, 225, 229, 235, 244, 251 Emboli, 204, 253 Embolism, 204, 238, 253 Embolization, 204, 253 Embolus, 204, 217 Embryo, 181, 193, 204, 216, 234 Emphysema, 96, 111, 117, 184, 204 Enamel, 201, 204, 208 Encephalopathy, 40, 72, 204 Endemic, 17, 204, 213, 245 Endocytosis, 37, 205 Endogenous, 22, 33, 85, 93, 115, 190, 191, 192, 203, 205, 237, 249 Endometriosis, 201, 205 Endothelial cell, 23, 30, 190, 205, 248 Endothelium, 205, 228 Endothelium-derived, 205, 228 Endotoxemia, 7, 26, 205 Endotoxic, 205, 221 Endotoxin, 6, 8, 29, 33, 69, 205, 250 Enhancer, 205, 240 Enteropeptidase, 205, 250 Environmental Exposure, 205, 229 Environmental Health, 4, 47, 61, 146, 148, 205 Enzymatic, 27, 184, 192, 197, 201, 205, 213 Enzyme Induction, 57, 205 Enzyme Inhibitors, 205, 234 Eosinophils, 183, 205, 211, 220 Epidemic, 26, 136, 170, 205, 245 Epidermis, 202, 205, 238 Epigastric, 205, 230 Epinephrine, 182, 203, 206, 228, 250 Epithelial, 182, 206, 213 Epithelial Cells, 206, 213 Epitope, 21, 206 Erythrocytes, 185, 191, 192, 206, 239 Erythromycin, 4, 206 Escalation, 11, 206 Esophagus, 202, 206, 209, 231, 232, 246, 252 Estrogens, 158, 206 Ethanol, 4, 5, 6, 9, 14, 16, 20, 21, 25, 33, 35, 50, 52, 77, 79, 93, 109, 183, 206, 207
260
Liver Damage
Ethnic Groups, 159, 163, 164, 206 Eukaryotic Cells, 206, 229, 251 Evacuation, 198, 206, 220 Excrete, 187, 206, 219 Exocrine, 206, 230 Exogenous, 26, 115, 190, 205, 206, 237 Exon, 13, 206 Expiration, 206, 240 Extensor, 206, 238 External-beam radiation, 206, 238 Extracellular, 24, 31, 111, 117, 198, 205, 206, 207, 208, 244 Extracellular Matrix, 198, 207, 208 Exudate, 207, 229 Eye Infections, 182, 207 F Failure to Thrive, 157, 207 Family Health, 125, 207 Family Planning, 147, 207 Fat, 26, 27, 108, 113, 130, 182, 187, 189, 190, 191, 192, 193, 199, 204, 207, 221, 234, 240, 242, 244, 250 Fatigue, 156, 162, 165, 170, 207, 212 Fatty acids, 27, 183, 207, 236 Fatty Liver, 8, 12, 14, 26, 27, 36, 112, 123, 130, 207 Fatty Liver, Alcoholic, 123, 207 Feces, 195, 198, 207 Felodipine, 110, 207 Fermentation, 183, 207 Ferritin, 43, 73, 207 Ferrochelatase, 13, 207 Fetal Alcohol Syndrome, 131, 207 Fetoprotein, 208 Fetus, 181, 184, 208, 236, 252 Fibrin, 190, 208, 248 Fibrinogen, 208, 234, 248 Fibroblasts, 110, 208 Fibrosis, 12, 14, 16, 20, 36, 45, 110, 112, 113, 198, 208, 241 Fine-needle aspiration, 208, 227 Fluid Therapy, 208, 229 Fluorescence, 23, 208 Fluorine, 63, 208 Fluorosis, 63, 208 Focus Groups, 6, 208 Fold, 5, 7, 10, 13, 208, 224 Forearm, 190, 208 Free Radicals, 59, 186, 203, 208, 226 Fulminant Hepatic Failure, 112, 208 Fungi, 198, 207, 208, 224, 254 Fungistatic, 208, 230
G Gadolinium, 50, 52, 208 Galactosemia, 72, 153, 209 Gallbladder, 96, 124, 125, 181, 189, 195, 200, 202, 209 Gallstones, 126, 189, 194, 195, 209, 251 Gamma Rays, 209, 238, 239 Gamma-Glutamyltransferase, 57, 209 Ganglia, 181, 209, 227, 232 Gap Junctions, 9, 198, 209 Gas, 184, 192, 202, 208, 209, 214, 228 Gastric, 46, 118, 168, 188, 192, 209, 213, 231 Gastric Juices, 209, 231 Gastrin, 209, 214 Gastritis, 5, 209 Gastroenterologist, 161, 209 Gastrointestinal, 169, 188, 191, 206, 209, 243, 246, 250 Gastrointestinal tract, 188, 206, 209, 243, 250 Gene Expression, 12, 13, 22, 209 Gene Therapy, 25, 182, 209 Genetic Counseling, 13, 210 Genetics, 153, 158, 198, 210 Genotype, 73, 76, 81, 111, 210, 232 Gestation, 210, 235 Giant Cells, 210, 241 Gland, 182, 199, 210, 222, 230, 231, 233, 237, 242, 246, 248 Glioma, 48, 210 Glomerular, 210, 219, 240 Glottis, 210, 232 Glucocorticoid, 202, 210 Gluconeogenesis, 210 Glucose, 48, 52, 114, 117, 188, 193, 209, 210, 212, 217, 218, 233, 241 Glutamate, 183, 210 Glutathione Peroxidase, 210, 242 Glycine, 184, 189, 194, 210, 228, 243 Glycogen, 114, 115, 117, 124, 129, 210, 233 Glycogen Storage Disease, 124, 210 Glycols, 210, 214 Glycoprotein, 111, 117, 184, 208, 210, 211, 248, 250 Glycosylation, 109, 211 Governing Board, 211, 235 Gp120, 211, 231 Graft, 24, 126, 211, 214, 216, 226 Graft Survival, 25, 211 Gram-negative, 69, 188, 191, 200, 205, 211, 228 Gram-Negative Bacteria, 69, 200, 205, 211
261
Gram-positive, 211, 228 Granulocyte, 10, 211 Granuloma, 32, 211 Growth factors, 11, 31, 211 Guanylate Cyclase, 211, 228 H Habitual, 194, 211 Haemophilus, 166, 211 Haemophilus influenzae, 166, 211 Haemorrhage, 181, 211 Haploid, 211, 234 Haptens, 182, 212 Headache, 212, 217 Health Education, 129, 163, 212 Health Promotion, 164, 212 Health Status, 207, 212 Heart failure, 166, 212 Heme, 189, 200, 207, 212, 226, 234, 235, 251 Hemochromatosis, 60, 64, 123, 125, 160, 212 Hemodialysis, 68, 76, 122, 123, 202, 212, 219, 220 Hemoglobin, 185, 189, 206, 212, 235, 247 Hemoglobin A, 212, 235 Hemoglobinopathies, 210, 212 Hemorrhage, 204, 212, 226, 238, 246 Hemostasis, 47, 212, 243 Hepatic Encephalopathy, 15, 130, 212 Hepatitis A, 7, 14, 122, 155, 159, 160, 165, 166, 170, 213 Hepatitis B, 55, 113, 152, 153, 154, 155, 158, 159, 161, 162, 164, 165, 170, 213 Hepatitis D, 73, 125, 213 Hepatitis Delta Virus, 73, 213 Hepatitis E, 170, 213 Hepatitis Viruses, 122, 130, 213 Hepatocellular carcinoma, 7, 13, 16, 17, 18, 32, 47, 59, 76, 127, 157, 161, 165, 213 Hepatocyte, 8, 14, 15, 16, 21, 31, 32, 33, 34, 36, 42, 55, 112, 117, 195, 213 Hepatocyte Growth Factor, 112, 213 Hepatologist, 161, 213 Hepatotoxic, 4, 111, 112, 118, 124, 213 Hepatotoxicity, 4, 8, 20, 29, 35, 111, 112, 124, 213 Hepatovirus, 213 Hereditary, 60, 124, 153, 184, 213, 247 Heredity, 209, 210, 213 Heterodimers, 13, 213 Heterogeneity, 182, 213 Histamine, 185, 213, 214 Histidine, 20, 213, 214
Histology, 29, 113, 126, 214 Homeostasis, 34, 214 Homodimer, 34, 214 Homologous, 183, 198, 209, 214, 247, 250 Hormonal, 188, 199, 214, 224 Hormone, 9, 64, 75, 116, 191, 199, 202, 206, 209, 214, 218, 219, 224, 240, 243, 248 Host, 16, 17, 27, 30, 32, 33, 56, 113, 188, 192, 211, 214, 216, 252, 253 Humoral, 113, 214 Humour, 214 Hyaluronidase, 74, 214 Hybrid, 20, 21, 195, 214 Hydrogen, 181, 183, 189, 192, 193, 210, 214, 221, 225, 228, 230, 237, 248, 254 Hydrogen Peroxide, 193, 210, 214, 221 Hydrolysis, 109, 190, 214, 233, 237, 250 Hydrophobic, 214, 221 Hydroxides, 214 Hydroxyl Radical, 29, 214 Hydroxylysine, 196, 214 Hydroxyproline, 184, 196, 214 Hyperammonemia, 15, 214 Hyperbilirubinemia, 124, 215, 219 Hypercholesterolemia, 23, 26, 27, 96, 215 Hyperlipidemia, 19, 27, 215 Hyperplasia, 66, 215 Hyperreflexia, 215, 247 Hypersensitivity, 41, 43, 112, 183, 202, 215, 240 Hypertension, 110, 199, 212, 215, 227, 235, 251 Hypertriglyceridemia, 26, 215 Hypertrophy, 31, 199, 215 Hypervascular, 47, 215 Hypogammaglobulinemia, 58, 215 Hypophyseal, 10, 215 Hypotensive, 118, 215 Hypothalamic, 10, 215 Hypothalamus, 215, 233 Hypoxia, 8, 215 Hypoxic, 56, 215 I Ibuprofen, 44, 215 Id, 86, 95, 170, 176, 178, 215 Idiopathic, 58, 75, 215, 241 Imidazole, 192, 213, 215 Immune Sera, 215, 216 Immune system, 22, 129, 162, 186, 188, 189, 215, 216, 222, 226, 227, 252, 253 Immunity, 30, 183, 216, 249 Immunization, 21, 130, 161, 216, 243
262
Liver Damage
Immunoassay, 27, 216 Immunodeficiency, 30, 130, 162, 165, 215, 216 Immunodeficiency syndrome, 130, 216 Immunogenic, 21, 216, 221 Immunoglobulin, 57, 58, 186, 216, 225 Immunologic, 194, 216, 239 Immunology, 22, 23, 41, 182, 216 Immunophilins, 9, 216, 244 Immunosuppressant, 183, 216, 224, 244 Immunosuppressive, 126, 136, 200, 210, 216, 247 Immunotherapy, 190, 202, 216 Impairment, 52, 130, 195, 207, 216, 224 Implant radiation, 216, 218, 239 In vitro, 11, 13, 19, 21, 22, 23, 32, 33, 35, 114, 209, 216, 247 In vivo, 11, 21, 23, 30, 32, 108, 114, 209, 216, 247 Incision, 216, 218 Incubated, 20, 216 Incubation, 216, 232 Incubation period, 216, 232 Indicative, 216, 231, 252 Induction, 9, 11, 16, 185, 216 Infancy, 75, 217 Infarction, 27, 217, 240 Infiltration, 16, 109, 217 Inflammatory bowel disease, 60, 217 Influenza, 8, 126, 217 Infusion, 22, 217, 226, 249 Ingestion, 37, 40, 52, 217, 234 Inhalation, 57, 182, 217, 234 Initiation, 20, 22, 217, 236, 249 Inlay, 217, 240 Inorganic, 214, 217, 225 Inositol, 9, 217 Inositol 1,4,5-Trisphosphate, 9, 217 Inotropic, 203, 207, 217 Insight, 18, 30, 32, 34, 217 Insomnia, 76, 218 Insulin, 27, 28, 35, 52, 69, 218, 241 Insulin-dependent diabetes mellitus, 218 Interferon, 18, 38, 60, 112, 125, 127, 154, 157, 159, 160, 161, 218, 222 Interferon-alpha, 218 Interleukin-1, 112, 113, 218 Interleukin-10, 112, 113, 218 Interleukin-2, 218 Internal Medicine, 21, 44, 60, 73, 85, 110, 112, 209, 218 Internal radiation, 218, 238
Interstitial, 191, 218, 240 Intestinal, 6, 60, 76, 115, 169, 188, 192, 194, 205, 218 Intestinal Mucosa, 188, 218 Intestine, 5, 169, 189, 191, 218, 220, 232 Intoxication, 40, 62, 68, 218, 254 Intracellular, 9, 12, 19, 24, 31, 217, 218, 228, 235, 237, 242, 243, 253 Intrahepatic, 32, 70, 218 Intramuscular, 218, 231 Intravascular, 39, 47, 48, 218 Intravenous, 11, 48, 58, 217, 218, 231 Intrinsic, 182, 218 Invasive, 4, 75, 216, 218, 222 Involuntary, 219, 226, 244 Iodine, 219, 224 Ionization, 22, 219 Ions, 189, 192, 203, 204, 207, 214, 217, 219, 237, 244 Ischemia, 23, 24, 29, 188, 219, 226, 240 Isoenzyme, 27, 199, 219 Isomerases, 216, 219 Isoniazid, 80, 98, 140, 219 J Jaundice, 75, 84, 125, 126, 157, 158, 164, 170, 215, 219 K Kava, 85, 89, 98, 134, 219 Kb, 146, 219 Keto, 219, 249 Kidney Failure, 169, 219 Kidney Failure, Acute, 219 Kidney Failure, Chronic, 219 Kidney Transplantation, 122, 220 Kinetic, 220 L Labile, 197, 220 Laceration, 220, 247 Lactate Dehydrogenase, 74, 220 Lactulose, 6, 220 Lamivudine, 154, 220 Large Intestine, 202, 218, 220, 239, 244 Laxative, 194, 220 Lectin, 220 Leprosy, 75, 220 Lethal, 9, 14, 31, 188, 203, 220 Leucocyte, 220, 222 Leukaemia, 60, 220 Leukemia, 51, 210, 220 Leukocytes, 189, 191, 194, 205, 218, 220, 250 Libido, 185, 220
263
Library Services, 176, 220 Life cycle, 190, 208, 220 Ligaments, 199, 221 Ligands, 11, 34, 221 Linkage, 26, 221 Lipid A, 23, 221 Lipid Peroxidation, 16, 20, 21, 22, 26, 55, 78, 108, 221, 230 Lipodystrophy, 27, 221 Lipofuscin, 67, 194, 221 Lipopolysaccharide, 10, 211, 221 Lipoprotein, 19, 38, 42, 59, 211, 221, 222, 253 Lithium, 65, 109, 221 Liver cancer, 6, 7, 17, 113, 125, 126, 127, 152, 153, 154, 156, 157, 161, 164, 165, 184, 221 Liver Cirrhosis, 65, 68, 96, 123, 161, 165, 221 Liver Mitochondria, 25, 221 Liver Regeneration, 31, 116, 221 Liver scan, 221, 242 Liver Transplantation, 24, 29, 47, 51, 56, 57, 71, 123, 126, 130, 152, 156, 157, 160, 163, 221 Lobe, 221 Lobule, 9, 221 Localization, 12, 24, 34, 116, 221 Localized, 181, 185, 201, 203, 217, 221, 222, 234, 247, 251 Lockjaw, 166, 222 Locomotion, 222, 234 Longitudinal study, 14, 222 Low-density lipoprotein, 221, 222 Lupus, 47, 136, 222, 247 Lymph, 188, 194, 205, 214, 222, 241 Lymph node, 188, 194, 222, 241 Lymphatic, 205, 217, 222, 241, 245, 248 Lymphatic system, 222, 241, 245, 248 Lymphoblastic, 222 Lymphoblasts, 13, 181, 222 Lymphocyte, 8, 186, 222, 223 Lymphocytic, 16, 222 Lymphoid, 186, 220, 222 Lysine, 20, 214, 222, 236, 250 Lytic, 222, 243 M Macrophage, 10, 218, 222 Magnetic Resonance Imaging, 222, 242 Maintenance therapy, 63, 223 Major Histocompatibility Complex, 39, 223
Malathion, 50, 223 Malignant, 182, 186, 221, 223, 227, 239 Malnutrition, 63, 130, 183, 188, 191, 223 Malondialdehyde, 20, 21, 22, 223 Manic, 221, 223 Manifest, 109, 223 Meat, 223, 242 Mediate, 8, 18, 21, 23, 26, 110, 203, 223 Mediator, 10, 12, 218, 223, 243 Medicament, 44, 223 MEDLINE, 147, 223 Mefloquine, 38, 40, 223 Melanin, 223, 232, 250 Melanocytes, 223 Melanoma, 72, 223 Membrane Fluidity, 25, 223 Memory, 201, 223 Meninges, 193, 224 Mental, iv, 4, 105, 130, 131, 146, 148, 162, 194, 201, 203, 207, 223, 224, 238, 242, 251 Mental deficiency, 207, 224 Mental Disorders, 105, 131, 224 Mental Health, iv, 4, 105, 146, 148, 224, 238 Mercaptopurine, 44, 224 Mesenteric, 188, 224, 235 Metabolic disorder, 36, 157, 210, 214, 224 Metabolite, 20, 29, 118, 190, 203, 224, 236 Methimazole, 109, 192, 224 Methionine, 25, 33, 34, 84, 203, 224, 246 Methotrexate, 56, 62, 63, 64, 70, 73, 75, 78, 80, 162, 224 Methyldopa, 54, 64, 70, 224 Methyltestosterone, 72, 224 MI, 44, 91, 93, 179, 224 Microbe, 224, 249 Microcirculation, 221, 224 Microorganism, 196, 224, 253 Microscopy, 15, 224 Microsomal, 57, 224 Milk Thistle, 43, 84, 90, 99, 100, 115, 225, 244 Mineralocorticoids, 182, 199, 225 Mitochondria, 8, 13, 24, 25, 225, 226, 229 Mitosis, 187, 225 Modeling, 64, 225 Modification, 19, 21, 35, 85, 93, 117, 184, 225, 238, 254 Molecule, 31, 33, 186, 189, 196, 197, 203, 204, 205, 206, 211, 212, 214, 219, 220, 225, 230, 233, 239, 243, 249, 252
264
Liver Damage
Monitor, 46, 49, 91, 114, 136, 158, 200, 225, 228 Monoclonal, 39, 55, 77, 225, 239 Monocyte, 18, 225 Mononuclear, 211, 225, 250 Morphine, 196, 225, 226, 229 Morphogenesis, 207, 225 Motility, 11, 225, 243 Motion Sickness, 225, 227 Motor Activity, 37, 199, 225 Mucins, 225, 241 Mucosa, 222, 225 Mucus, 168, 225, 251 Muscle relaxant, 225, 232, 247 Muscle Spindles, 225, 232 Mutagenic, 183, 203, 226 Myalgia, 217, 226 Myocardial infarction, 199, 224, 226, 253 Myocardial Ischemia, 185, 226 Myocardial Reperfusion, 226, 240 Myocardial Reperfusion Injury, 226, 240 Myocarditis, 203, 226 Myocardium, 185, 224, 226 Myofibrils, 192, 226 Myoglobin, 226, 235 Myopathy, 77, 226 N Naive, 159, 226 Narcosis, 226 Narcotic, 62, 140, 225, 226 Nasal Mucosa, 217, 227 Nausea, 122, 136, 158, 162, 165, 170, 227, 251 NCI, 1, 103, 104, 145, 195, 227 Needle biopsy, 15, 208, 227 Neonatal, 123, 227 Neoplasia, 31, 227 Neoplasm, 227, 250 Neoplastic, 112, 227 Neopterin, 7, 227 Nephrologist, 122, 227 Nerve, 182, 185, 194, 201, 223, 227, 229, 231, 235, 246, 250 Nervous System, 193, 223, 227, 232 Neural, 191, 208, 214, 227, 244 Neural tube defects, 208, 227 Neuromuscular, 181, 227, 251 Neuromuscular Junction, 181, 227 Neurons, 196, 201, 209, 225, 227, 247 Neuropathy, 118, 227, 254 Neuropeptide, 191, 227 Neurophysiology, 202, 227
Neurotransmitter, 181, 184, 191, 203, 210, 214, 228, 243, 246 Neutrons, 184, 228, 238 Neutrophil, 111, 117, 157, 184, 228 Nevirapine, 228 Nifedipine, 110, 228 Nitric Oxide, 6, 10, 29, 228 Nitrofurantoin, 42, 228 Nitrogen, 183, 185, 200, 219, 228, 250 Non-nucleoside, 154, 201, 228 Norepinephrine, 182, 203, 224, 228 Normotensive, 39, 228 Nuclear, 19, 30, 33, 34, 116, 198, 206, 209, 228, 251 Nuclei, 184, 198, 209, 222, 225, 228, 229, 237, 241 Nucleic acid, 189, 228, 240, 253, 254 Nucleoprotein, 213, 229 Nucleus, 24, 34, 187, 189, 195, 200, 205, 206, 209, 225, 228, 229, 237 Nutritional Status, 68, 71, 229 Nutritional Support, 123, 229 O Oliguria, 219, 229 Oncogene, 72, 213, 229 Opacity, 201, 229 Opium, 48, 225, 229, 230 Opportunistic Infections, 131, 229 Optic Nerve, 229, 240 Organ Transplantation, 118, 229 Organelles, 193, 200, 223, 229 Osmotic, 183, 229 Osteoclasts, 191, 229 Overdose, 47, 48, 52, 66, 67, 70, 208, 229 Overexpress, 19, 229 Oxacillin, 196, 229 Oxidation, 6, 20, 108, 181, 186, 190, 200, 210, 221, 224, 230 Oxidation-Reduction, 190, 230 Oxidative metabolism, 9, 182, 230 Oxidative Stress, 15, 16, 22, 26, 28, 34, 71, 230 Oxygen Consumption, 230, 240 Oxyquinoline, 4, 230 P Palliative, 230, 247 Pancreas, 44, 125, 168, 181, 190, 202, 209, 212, 218, 230, 245, 250 Pancreatic, 192, 230 Pancreatitis, 5, 44, 230 Papaverine, 229, 230 Paralysis, 166, 230
265
Parasite, 32, 230, 242 Parasitic, 32, 43, 109, 110, 230 Parenteral, 67, 230, 231 Parenteral Nutrition, 67, 231 Parotid, 231, 241 Paroxysmal, 185, 231, 232, 253 Partial remission, 231, 239 Pathogenesis, 16, 17, 18, 23, 28, 30, 32, 56, 67, 69, 72, 122, 231 Pathologic, 44, 187, 190, 199, 215, 231, 238 Pathologic Processes, 187, 231 Pathophysiology, 28, 123, 231 Patient Education, 130, 152, 168, 174, 176, 179, 231 Patient Selection, 154, 231 Pelvis, 181, 231, 251 Penis, 198, 204, 231 Pepsin, 231 Peptic, 168, 231 Peptic Ulcer, 168, 231 Peptide, 8, 16, 20, 27, 37, 61, 75, 184, 191, 205, 209, 231, 236, 237, 239 Peptide T, 8, 20, 231 Perforation, 169, 231 Perfusion, 215, 231, 248 Peripheral Nervous System, 224, 228, 232, 246 Peripheral stem cell transplantation, 103, 232 Peristalsis, 118, 232 Perivascular, 191, 232 Peroxide, 29, 232 Pertussis, 166, 232, 253 Phagocytosis, 115, 117, 232 Pharmacokinetic, 232 Pharmacologic, 185, 232, 248, 249 Pharynx, 217, 232 Phenotype, 5, 13, 232 Phenyl, 50, 110, 118, 232 Phenylalanine, 232, 250 Phenytoin, 45, 68, 232 Phlebotomy, 158, 233 Phospholipases, 233, 243 Phospholipids, 207, 217, 221, 223, 233 Phosphorus, 191, 233 Phosphorylase, 192, 233 Phosphorylation, 9, 22, 25, 37, 233 Photoallergy, 233 Photocoagulation, 196, 233 Photosensitivity, 13, 233, 235 Physical Examination, 4, 233 Physiologic, 183, 233, 236, 239, 250
Physiology, 15, 84, 85, 93, 155, 156, 161, 209, 227, 233 Pigments, 189, 192, 233 Pilot study, 30, 233 Pituitary Gland, 199, 233 Plants, 36, 183, 192, 194, 195, 196, 210, 220, 228, 233, 234, 241, 249 Plasma cells, 186, 234 Plasma protein, 115, 183, 234, 237 Platelet Activation, 234, 244 Platelet Aggregation, 185, 228, 234 Platelets, 192, 228, 234, 243, 248 Pneumonia, 198, 234 Poisoning, 37, 67, 71, 194, 202, 218, 221, 227, 234 Pollen, 234, 238 Polymerase, 187, 234, 236 Polymorphism, 13, 42, 234 Polyneuritis, 203, 234 Polysaccharide, 186, 193, 234 Polyunsaturated fat, 27, 91, 234 Polyvinyl Chloride, 64, 234 Porphyria, 39, 49, 91, 123, 158, 233, 234, 235 Porphyria Cutanea Tarda, 39, 49, 91, 123, 158, 233, 235 Porphyria, Hepatic, 235 Porphyrins, 158, 234, 235 Portal Hypertension, 62, 79, 157, 235 Portal Vein, 157, 235 Portography, 47, 235 Posterior, 185, 195, 230, 235 Postnatal, 207, 235, 245 Postsynaptic, 235, 243 Potassium, 108, 225, 235 Potentiate, 8, 235 Potentiation, 235, 243 Practice Guidelines, 148, 235 Preclinical, 134, 235 Precursor, 31, 33, 187, 195, 200, 203, 204, 205, 227, 228, 232, 235, 236, 237, 250, 251 Pre-Eclampsia, 74, 235 Pregnancy Maintenance, 206, 236 Prenatal, 204, 207, 236 Prevalence, 3, 14, 122, 236 Primary Biliary Cirrhosis, 56, 74, 79, 109, 110, 125, 156, 236 Primary Sclerosing Cholangitis, 125, 236 Procollagen, 75, 236 Prodrug, 118, 236 Progeny, 198, 236
266
Liver Damage
Progression, 8, 12, 17, 18, 25, 31, 36, 47, 56, 74, 76, 112, 152, 185, 236 Progressive disease, 113, 236 Proline, 196, 214, 236 Promoter, 13, 46, 65, 236 Promotor, 236, 240 Prone, 9, 236 Prophylaxis, 58, 187, 228, 236, 252, 253 Prospective study, 56, 71, 73, 222, 236 Prostaglandin, 33, 118, 236 Prostaglandins A, 236, 237 Prostate, 190, 237, 250 Protease, 184, 197, 237 Protein Binding, 237, 248 Protein C, 11, 183, 184, 187, 188, 196, 207, 221, 237, 251, 253 Protein Conformation, 184, 237 Protein S, 187, 190, 203, 206, 237 Proteinuria, 235, 237 Proteolytic, 184, 197, 205, 208, 237 Prothrombin, 49, 237, 248 Protocol, 4, 14, 111, 237 Protons, 184, 214, 237, 238 Protozoa, 198, 224, 238 Proximal, 203, 238 Psoriasis, 63, 70, 75, 162, 238 Psychic, 220, 224, 238, 242 Psychoactive, 238, 254 Public Health, 17, 31, 32, 37, 40, 84, 148, 238 Public Policy, 147, 238 Pulmonary, 95, 184, 190, 198, 199, 219, 238, 253 Pulmonary Artery, 190, 238 Pulmonary Edema, 219, 238 Pulmonary Embolism, 238, 253 Pulse, 225, 238 Purifying, 108, 156, 238 Purpura, 58, 211, 238 Pyridoxal, 43, 238, 249 Q Quality of Life, 6, 238 Quercetin, 91, 94, 95, 238 R Race, 28, 170, 238 Radiation, 85, 108, 109, 121, 185, 200, 205, 206, 208, 209, 218, 238, 239, 242, 254 Radiation therapy, 121, 206, 218, 238 Radioactive, 191, 214, 216, 218, 219, 221, 228, 238, 239, 242, 251 Radiolabeled, 239 Radiotherapy, 191, 239
Randomized, 28, 52, 204, 239 Ras gene, 72, 239 Reactivation, 54, 239 Reactive Oxygen Species, 8, 16, 19, 24, 30, 239 Reagent, 230, 239, 248 Receptor, 9, 11, 19, 23, 31, 33, 34, 37, 58, 93, 118, 186, 203, 211, 213, 231, 239, 243 Recombinant, 24, 239, 252 Recombination, 198, 209, 239 Rectum, 187, 191, 196, 202, 209, 217, 220, 237, 239 Recurrence, 126, 239 Red blood cells, 206, 235, 239, 241 Reductase, 224, 239 Refer, 1, 191, 197, 208, 221, 222, 226, 228, 239, 249 Refraction, 239, 245 Refractory, 11, 204, 239 Regeneration, 31, 239 Regimen, 204, 239 Relapse, 10, 109, 131, 239 Remission, 38, 127, 223, 239 Renal failure, 54, 240, 251 Reperfusion, 23, 24, 29, 226, 240 Reperfusion Injury, 23, 240 Respiration, 8, 192, 225, 240 Response Elements, 34, 240 Response rate, 11, 240 Restoration, 31, 112, 226, 239, 240, 254 Reticular, 9, 240 Retina, 118, 195, 229, 240, 241, 253 Retinoid, 34, 240 Retinol, 34, 240 Retrospective, 30, 240 Retroviral vector, 209, 240 Rheumatism, 215, 240 Rheumatoid, 48, 62, 162, 195, 240 Rheumatoid arthritis, 48, 62, 162, 195, 240 Ribavirin, 112, 126, 240 Riboflavin, 76, 241 Ribonuclease, 20, 241 Rigidity, 234, 241 Risk factor, 8, 14, 16, 26, 28, 31, 36, 66, 126, 152, 154, 160, 161, 162, 165, 168, 170, 236, 241 Rod, 189, 205, 211, 241 Rosiglitazone, 35, 241 Rubber, 234, 241 Rubella, 166, 241 Rutin, 238, 241
267
S Salicylate, 44, 241 Saliva, 163, 241 Salivary, 202, 241 Salivary glands, 202, 241 Saponins, 192, 241, 245 Sarcoidosis, 73, 96, 241 Satellite, 213, 241 Saturated fat, 27, 242 Scans, 80, 242 Schistosome, 33, 242 Schizoid, 242, 253 Schizophrenia, 242, 253 Schizotypal Personality Disorder, 242, 253 Screening, 4, 17, 36, 44, 62, 114, 116, 136, 152, 160, 195, 242 Secretion, 9, 10, 32, 111, 115, 117, 118, 199, 213, 214, 218, 225, 242, 252 Sedative, 196, 219, 242 Sedimentation, 193, 242, 250 Seizures, 231, 232, 242 Selenium, 94, 242 Self Care, 124, 242 Semen, 164, 204, 237, 242 Sensibility, 185, 242 Sepsis, 188, 243 Sequence Homology, 231, 243 Sequester, 194, 243 Serine, 243, 250 Seroconversion, 65, 243 Serologic, 17, 126, 216, 243 Serotonin, 228, 243, 250 Sertraline, 40, 243 Serum, 7, 8, 11, 14, 20, 23, 26, 27, 28, 44, 45, 49, 50, 56, 57, 70, 73, 74, 75, 76, 91, 113, 117, 183, 185, 197, 199, 215, 219, 222, 225, 243, 250 Sex Characteristics, 185, 206, 243 Sexual Partners, 159, 243 Shock, 23, 29, 205, 243, 250 Side effect, 11, 57, 108, 116, 121, 131, 136, 139, 161, 162, 182, 190, 200, 223, 243, 249, 254 Siderosis, 123, 243 Signal Transduction, 9, 24, 33, 217, 243 Signs and Symptoms, 166, 239, 244, 251 Silymarin, 91, 115, 225, 244 Sirolimus, 216, 244 Skeletal, 185, 199, 225, 226, 244 Skeleton, 181, 236, 244 Skull, 227, 244, 247
Small intestine, 168, 194, 195, 200, 204, 214, 218, 244, 250 Smoking Cessation, 169, 244 Smooth muscle, 184, 185, 192, 207, 214, 225, 230, 244, 246 Sneezing, 167, 169, 232, 244 Social Environment, 238, 244 Sodium, 68, 108, 140, 225, 244, 252 Sodium Channels, 244, 252 Soft tissue, 191, 244 Solvent, 206, 229, 244 Soma, 244 Somatic, 34, 214, 225, 232, 244 Soybean Oil, 234, 244 Spasmodic, 232, 244 Specialist, 122, 171, 202, 245 Species, 18, 30, 35, 101, 184, 193, 196, 206, 211, 214, 225, 229, 230, 238, 239, 243, 245, 246, 250, 253, 254 Specificity, 182, 245, 248 Spectrum, 22, 76, 157, 223, 245 Sperm, 167, 168, 169, 185, 195, 234, 245, 250 Spinal cord, 193, 195, 224, 227, 232, 245 Spleen, 185, 188, 222, 241, 245 Splenic Vein, 235, 245 Sporadic, 235, 245 Stabilization, 232, 245 Staging, 242, 245 Steatosis, 8, 13, 20, 25, 74, 76, 207, 245 Steel, 116, 245 Stellate, 15, 22, 245 Stem cell transplantation, 103, 201, 245 Stem Cells, 11, 232, 245 Stenosis, 245, 246 Sterile, 155, 245 Sterility, 200, 245 Steroid, 189, 199, 201, 241, 245 Stimulant, 213, 246, 247 Stimulus, 246, 248 Stomach, 5, 122, 168, 181, 188, 202, 206, 209, 214, 227, 231, 232, 244, 245, 246 Street Drugs, 155, 163, 164, 167, 169, 246 Stress, 17, 24, 26, 29, 33, 117, 122, 124, 170, 199, 227, 230, 240, 241, 246 Stricture, 52, 245, 246 Stroke, 105, 146, 246 Stroma, 243, 246 Stupor, 226, 246 Subacute, 25, 217, 246 Subclinical, 113, 217, 242, 246 Subcutaneous, 204, 221, 231, 246
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Liver Damage
Subspecies, 245, 246 Substance P, 206, 224, 242, 246 Sulfur, 220, 224, 246 Superoxide, 29, 43, 246 Supplementation, 12, 26, 85, 94, 246 Support group, 131, 157, 246 Suppression, 38, 55, 199, 228, 246 Suppressive, 118, 136, 246 Symptomatic, 13, 230, 247 Synaptic, 228, 243, 247 Synergistic, 21, 247 Systemic, 26, 48, 131, 140, 185, 188, 190, 195, 203, 206, 217, 239, 241, 247, 249, 253 Systemic lupus erythematosus, 195, 247 Systemic therapy, 195, 247 Systolic, 215, 247 T Tacrine, 100, 162, 247 Tacrolimus, 216, 247 Taurine, 189, 194, 247 Temporal, 23, 25, 30, 247 Terminator, 196, 247, 254 Tetani, 247 Tetanic, 247 Tetanus, 166, 247 Thalassemia, 189, 247 Therapeutics, 141, 247 Thermal, 29, 203, 228, 247 Thiamine, 76, 247 Thioacetamide, 93, 248 Thorax, 181, 248 Threonine, 231, 243, 248 Threshold, 4, 215, 248 Thrombin, 208, 234, 237, 248 Thrombomodulin, 237, 248 Thrombosis, 49, 80, 237, 246, 248 Thrombus, 199, 217, 226, 234, 248, 252 Thymus, 216, 222, 248 Thyroid, 38, 40, 75, 191, 219, 224, 248, 250 Thyroid Gland, 248 Thyroid Hormones, 224, 248, 250 Thyroxine, 56, 78, 183, 232, 248 Tissue Distribution, 27, 248 Tolerance, 9, 15, 79, 182, 248 Tomography, 17, 197, 242, 248 Tone, 228, 248 Tonic, 222, 248 Topical, 206, 214, 230, 249 Torsion, 217, 249 Toxicity, 11, 16, 25, 29, 33, 41, 59, 62, 89, 108, 114, 203, 246, 249 Toxicokinetics, 249
Toxicology, 29, 35, 40, 50, 78, 80, 148, 249 Toxin, 51, 124, 203, 205, 247, 248, 249 Trace element, 71, 208, 249 Trachea, 232, 248, 249 Transaminase, 8, 45, 75, 113, 122, 249 Transcriptase, 201, 220, 228, 249, 254 Transcription Factors, 240, 249 Transduction, 24, 243, 249 Transfection, 190, 209, 249 Transfer Factor, 216, 249 Transferases, 211, 249 Transfusion, 136, 213, 249 Translation, 184, 206, 249 Translational, 6, 250 Translocating, 188, 250 Translocation, 10, 33, 188, 206, 250 Transmitter, 181, 203, 223, 224, 228, 250 Transplantation, 23, 25, 31, 44, 47, 51, 55, 56, 57, 68, 71, 73, 126, 216, 223, 232, 250 Trauma, 62, 112, 212, 230, 250 Tremor, 65, 250 Triglyceride, 215, 250 Triolein, 80, 250 Troglitazone, 35, 250 Trypsin, 20, 184, 205, 250, 254 Tryptophan, 196, 243, 250 Tuberculostatic, 219, 250 Tubulin, 7, 250 Tumor marker, 190, 250 Tumor Necrosis Factor, 21, 110, 250 Tumour, 41, 48, 250 Tyrosine, 25, 203, 250 U Ubiquitin, 111, 118, 251 Ulcer, 204, 251 Ulceration, 231, 251 Ulcerative colitis, 217, 236, 251 Unconscious, 215, 251 Univalent, 214, 230, 251 Unresectable, 59, 251 Uraemia, 230, 251 Uranium, 134, 251 Urea, 115, 219, 251 Uremia, 48, 219, 240, 251 Urethra, 231, 237, 251 Urinary, 6, 15, 67, 80, 228, 229, 251 Urinary tract, 228, 251 Urinary tract infection, 228, 251 Urine, 15, 43, 158, 187, 190, 199, 200, 219, 229, 237, 241, 251 Uroporphyrinogen Decarboxylase, 158, 235, 251
269
Ursodeoxycholic Acid, 45, 49, 251 Uterine Contraction, 181, 251 Uterus, 181, 194, 251, 252 V Vaccination, 122, 152, 153, 161, 162, 167, 252 Vaccine, 154, 155, 162, 164, 182, 237, 252 Vacuoles, 205, 229, 252 Vagina, 194, 202, 252 Vaginal, 159, 164, 252 Valproic Acid, 45, 51, 252 Varicella, 166, 252 Varices, 50, 252 Vascular, 112, 195, 202, 205, 207, 217, 221, 224, 228, 248, 252 Vasculitis, 41, 230, 252 Vasodilation, 110, 230, 252 Vasodilator, 191, 203, 214, 226, 228, 230, 252 Vector, 249, 252 Vein, 77, 185, 218, 228, 231, 233, 235, 241, 245, 252 Venlafaxine, 40, 252 Venous, 52, 237, 252, 253 Venous Thrombosis, 252, 253 Verapamil, 60, 110, 252 Vesicular, 224, 252 Veterinary Medicine, 147, 252 Vinblastine, 250, 252 Vincristine, 250, 252 Viral Hepatitis, 21, 32, 69, 73, 76, 96, 109, 123, 126, 155, 156, 160, 169, 170, 252
Viral Load, 14, 252 Viremia, 14, 113, 253 Virion, 213, 253 Virulence, 249, 253 Virus Diseases, 187, 253 Virus Replication, 50, 253 Visceral, 76, 253 Viscosity, 214, 253 Vitamin A, 87, 217, 240, 253 Vitreous, 240, 253 Vitreous Body, 240, 253 Vitro, 33, 253 Vivo, 30, 108, 253 W Warfarin, 6, 80, 253 Weight Gain, 207, 253 White blood cell, 157, 181, 186, 211, 216, 220, 222, 225, 228, 234, 253 Whooping Cough, 166, 232, 253 Windpipe, 232, 248, 253 Withdrawal, 80, 123, 253 Wound Healing, 31, 254 X Xenograft, 185, 254 X-ray, 187, 193, 197, 208, 209, 228, 235, 238, 239, 242, 254 Y Yeasts, 208, 232, 254 Z Zalcitabine, 220, 254 Zygote, 198, 254 Zymogen, 237, 254
270
Liver Damage
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272
Liver Damage
