ACETAMINOPHEN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
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., 1960Acetaminophen: 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: 0-597-84319-8 1. Acetaminophen-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 acetaminophen. 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 ACETAMINOPHEN .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Acetaminophen ............................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 44 The National Library of Medicine: PubMed ................................................................................ 45 CHAPTER 2. NUTRITION AND ACETAMINOPHEN........................................................................... 91 Overview...................................................................................................................................... 91 Finding Nutrition Studies on Acetaminophen ............................................................................ 91 Federal Resources on Nutrition ................................................................................................... 95 Additional Web Resources ........................................................................................................... 96 CHAPTER 3. ALTERNATIVE MEDICINE AND ACETAMINOPHEN .................................................... 99 Overview...................................................................................................................................... 99 National Center for Complementary and Alternative Medicine.................................................. 99 Additional Web Resources ......................................................................................................... 109 General References ..................................................................................................................... 116 CHAPTER 4. DISSERTATIONS ON ACETAMINOPHEN .................................................................... 117 Overview.................................................................................................................................... 117 Dissertations on Acetaminophen ............................................................................................... 117 Keeping Current ........................................................................................................................ 118 CHAPTER 5. CLINICAL TRIALS AND ACETAMINOPHEN ............................................................... 119 Overview.................................................................................................................................... 119 Recent Trials on Acetaminophen ............................................................................................... 119 Keeping Current on Clinical Trials ........................................................................................... 120 CHAPTER 6. PATENTS ON ACETAMINOPHEN ............................................................................... 123 Overview.................................................................................................................................... 123 Patents on Acetaminophen ........................................................................................................ 123 Patent Applications on Acetaminophen..................................................................................... 148 Keeping Current ........................................................................................................................ 160 CHAPTER 7. BOOKS ON ACETAMINOPHEN ................................................................................... 161 Overview.................................................................................................................................... 161 Book Summaries: Federal Agencies............................................................................................ 161 Book Summaries: Online Booksellers......................................................................................... 163 Chapters on Acetaminophen ...................................................................................................... 164 CHAPTER 8. PERIODICALS AND NEWS ON ACETAMINOPHEN ..................................................... 169 Overview.................................................................................................................................... 169 News Services and Press Releases.............................................................................................. 169 Newsletter Articles .................................................................................................................... 173 Academic Periodicals covering Acetaminophen......................................................................... 174 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 175 Overview.................................................................................................................................... 175 U.S. Pharmacopeia..................................................................................................................... 175 Commercial Databases ............................................................................................................... 177 Researching Orphan Drugs ....................................................................................................... 178 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 181 Overview.................................................................................................................................... 181 NIH Guidelines.......................................................................................................................... 181 NIH Databases........................................................................................................................... 183 Other Commercial Databases..................................................................................................... 185 The Genome Project and Acetaminophen .................................................................................. 185
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APPENDIX B. PATIENT RESOURCES ............................................................................................... 189 Overview.................................................................................................................................... 189 Patient Guideline Sources.......................................................................................................... 189 Finding Associations.................................................................................................................. 199 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 201 Overview.................................................................................................................................... 201 Preparation................................................................................................................................. 201 Finding a Local Medical Library................................................................................................ 201 Medical Libraries in the U.S. and Canada ................................................................................. 201 ONLINE GLOSSARIES................................................................................................................ 207 Online Dictionary Directories ................................................................................................... 209 ACETAMINOPHEN DICTIONARY.......................................................................................... 211 INDEX .............................................................................................................................................. 297
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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 acetaminophen 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 acetaminophen, 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 acetaminophen, 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 acetaminophen. 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 acetaminophen, 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 acetaminophen. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON ACETAMINOPHEN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on acetaminophen.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and acetaminophen, 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 “acetaminophen” (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: •
Acute Renal Failure Due to Acetaminophen Ingestion: A Case Report and Review of the Literature Source: Journal of the American Society of Nephrology. 6(1): 48-53. July 1995. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201. (800) 638-0672 or (410) 528-4000. Summary: Acetaminophen is the most commonly reported drug overdose in the U.S. In this article, the authors present a case report of acute renal failure (ARF) due to acetaminophen ingestion and review the relevant literature. They note that, at therapeutic dosages, acetaminophen can be toxic to the kidneys in patients who are glutathione depleted (chronic alcohol injection, starvation, or fasting) or who take drugs that stimulate the P-450 microsomal oxidase enzymes (anticonvulsants). Acute renal
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Acetaminophen
failure due to acetaminophen manifests as acute tubular necrosis (ATN), either alone or in combination with hepatic necrosis. The azotemia of acetaminophen toxicity is typically reversible, although it may worsen over 7 to 10 days before the recovery of renal function occurs. The authors stress that recognition of acetaminophen nephropathy requires the following: a thorough drug history, including over-thecounter medications such as Tylenol or Nyquil; knowledge of the risk factors that lessen its margin of safety at therapeutic ingestions; and consideration of acetaminophen in the differential diagnosis of patients who present with combined hepatic dysfunction and ATN. 1 figure. 5 tables. 21 references. (AA-M). •
Severe Hepatotoxicity, Acute Renal Failure, and Pancytopenia in a Young Child After Repeated Acetaminophen Overdosing Source: Clinical Pediatrics. 33(1): 42-45. January 1994. Contact: Available from Cortlandt Group. 500 Executive Boulevard, Ossining, NY 10562. Summary: In this article, the authors report the case of a young child who developed severe hepatotoxicity, renal failure, and pancytopenia after repeated acetaminophen overdosing and who survived after supportive treatment and late N-acetylcysteine therapy. The 3.5-year-old child had received 320 mg of acetaminophen every 2 hours for at least 48 hours. This dose is the equivalent of about 25 mg/kg of body weight every 2 hours, which exceeds the recommended therapeutic dose of 10 to 20 mg/kg every 4 hours. The patient received Mucomyst 36 hours after the last acetaminophen dose, for a total of 18 doses in addition to peritoneal dialysis. On follow-up a week later, all laboratory parameters were normal. The authors hypothesize that the bone marrow depression in this patient may have been caused by acetaminophen toxicity as a direct effect of the acetaminophen toxic metabolite. N-acetylcysteine therapy may have had a role in this patient's recovery despite late administration. 1 table. 14 references.
•
Recognizing Acetaminophen Hepatotoxicity in Chronic Alcoholics Source: Postgraduate Medicine. 91(4): 241-245. March 1992. Summary: The authors of this article discuss the metabolism of acetaminophen and describe how it differs in chronic alcoholics and suicidal patients who overdose. The mechanism of increased susceptibility involves induction of isoenzymes of the cytochrome P-450 system by alcohol and depletion of hepatic glutathione reserves, both of which can result from chronic alcohol ingestion and both of which affect the metabolism of acetaminophen. In addition, the authors compare the presentation of acetaminophen hepatotoxicity with that of alcoholic hepatitis. 1 figure. 3 tables. 3 references. (AA-M).
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Risk of Kidney Failure Associated With the Use of Acetaminophen, Aspirin, and Nonsteroidal Antiinflammatory Drugs Source: New England Journal of Medicine. 331(25): 1675-1679. December 22, 1994. Summary: This article reports on a case-control study of 716 patients treated for endstage renal disease (ESRD) and 361 control subjects to determine the risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs (NSAIDs). The study participants were interviewed by telephone about their past use of these medications. For each analgesic drug, the average use (in pills per year) and the cumulative intake (in pills) were examined for any association with ESRD. Heavier acetaminophen use was associated with an
Studies
5
increased risk of ESRD in a dose-dependent fashion. When persons who took an average of 0 to 104 pills per year were used for reference, the odds ratio of ESRD was 1.4 for those who took 105 to 365 pills per year; and 2.1 for those who took 366 or more pills per year, after adjustment for race, sex, age, and intake of other analgesic drugs. Approximately 8 to 10 percent of the overall incidence of ESRD was attributable to acetaminophen use. 5 tables. 17 references. •
Outcome of Acetaminophen Overdose in Pediatric Patients and Factors Contributing to Hepatotoxicity Source: Journal of Pediatrics. 130(2): 300-304. February 1997. Summary: This article reports on a study that investigated the outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatoxicity. The medical records of 73 pediatric patients admitted for acetaminophen overdose were reviewed. Twenty-eight patients (39 percent) had severe liver toxic effects, and 6 of them underwent liver transplantation. Multiple miscalculated overdoses given by parents, with delay in therapy, are risk factors and the major cause of overdose in children 10 years of age or younger. Factors contributing to toxic effects are multiple overdosing, delayed referral and therapy, and concomitant ingestion of 'enzyme inducers.' Time should be spent in educating caregivers regarding proper dosing and warning them of the dangers of overingestion. Health care providers should always include a detailed history of medications taken by the patient to avoid missing a diagnosis of overdose and to avoid delay in management. The article is accompanied by a related editorial from the same issue. 1 figure. 2 tables. 30 references. (AA-M).
Federally Funded Research on Acetaminophen The U.S. Government supports a variety of research studies relating to acetaminophen. 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 acetaminophen. 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 acetaminophen. The following is typical of the type of information found when searching the CRISP database for acetaminophen: •
Project Title: A MULTI-CENTER THERAPY TRIAL FOR ACUTE LIVER FAILURE Principal Investigator & Institution: Lee, William M.; Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105
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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Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (provided by applicant): The Acute Liver Failure Study Group (ALFSG) goals are to advance knowledge and understanding of acute liver failure through a multicenter approach including data, serum and DNA collection, and a therapeutic trial of Nacetylcysteine (NAC) for non-acetaminophen acute liver failure. At the beginning the third year of this grant, several specific additional funding needs have been identified. The purpose of this competing supplement is to request increased funding for an expanded scope of work, specifically in 3 areas: 1) Twelve additional sites have been added to the study group in order to fulfill the group's main goal, the completion of the N-acetylcysteine trial. The original plan called for 15 adult sites; we now have 27 sites participating, necessitated by the slower than expected enrollment in the therapy trial. The administrative costs required to support the additional sites are requested, to ensure the trial's completion. 2) A long-term follow-up study and the acquisition of DNA samples in addition of sera have been added to the original data and serum registry. The original study had no provision for study of patient outcomes past their initial hospitalization. DNA samples had not originally been anticipated but provide a valuable resource for future investigations. 3) Funding is requested for several ancillary studies not anticipated at the time of the original grant, all targeted toward a better understanding of the pathogenesis of ALF. These include 1) analysis of the role of apoptotic markers, 2) study of the role of heavy metals and reactive oxygen species, and 3) a study of acetaminophen adducts as markers of liver injury due to acetaminophen toxicity. To date, several ancillary studies have been accomplished within the current grant budget. These three ancillary studies require additional support beyond that anticipated in the original grant submission. To seize the opportunities now present, we request additional funding in 3 areas: central site resources for full implementation of the NAC trial and DNA sample handling, the long-term follow-up study and to fully utilize the rich clinical material available for ancillary studies closely related to acute liver failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A PHARMACOKINETIC STUDY OF GLUCOSAMINE AND CHONDROITIN Principal Investigator & Institution: Jackson, Christopher G.; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2004; Project Start 15-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Osteoarthritis is the most common musculoskeletal disease in the United States and throughout the world. While predisposing conditions have been identified, the actual cause of osteoarthritis remains unknown and therapy at present is limited to relief of symptoms. Traditional treatments, most often nonsteroidal anti-inflammatory drugs and nonnarcotic analgesics such as acetaminophen, produce variable efficacy and may be complicated by significant toxicity. The use of alternative and complementary therapies in the treatment of osteoarthritis is common and particular interest has focused on glucosamine and chondroitin preparations. Numerous anecdotal and preliminary reports with these agents have ted to present NIAMS/NCCAM sponsored Glucosamine Arthritis Intervention Trial (GAIT). The specific aims of this multi-center trial are to determine to determine the efficacy of glucosamine, chondroitin, and the combination in relieving the symptoms of knee osteoarthritis and to investigate the possibility of a chondroprotective effect. A number of biologic actions have been attributed to glucosamine and chondroitin but no convincing mechanism of action is apparent. The specific aim of this study is to
Studies
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determine the single-dose and multiple-dose pharmacokinetics of these agents when used individually as well as in combination. The study medications and dosing regimens to be investigated are those being utilized in GAIT. A better understanding of the pharmacokinetics of these agents may provide a more rational basis for future clinical investigations as well as suggesting potential sites and mechanisms of action. Pharmacokinetic studies of glucosamine and chondroitin to date have been limited by uncertain product quality, study design, sample size, and problematic assay methods. The present availability of a plasma assay that is sensitive and specific combined with a properly designed and controlled pharmacokinetic trial on a sufficient number of human subjects will provide the necessary information to fully characterize both the single-dose and steady-state pharmacokinetics of each of these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE-RELATED CHANGES IN GLUTATHIONE SYNTHESIS Principal Investigator & Institution: Fukagawa, Naomi K.; Associate Professor of Medicine; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Oxidative stress is thought to be one of the mechanisms leading to the initiation or progression of specific diseases as well as to the general process of aging. Glutathione (GSH), a tripeptide present in high concentrations in all mammalian cells, is the body's major endogenous antioxidant and plays a vital role in detoxification reactions and in the protection of cells from the toxic effects of oxidants. Maintenance of body GSH stores is a complex, integrated phenomenon, and there has been a resurgence of interest in potential interventions that may modulate GSH levels in the whole body and in specific tissues and cells. Advancing age, known to be associated with increased oxidative stress, is also reported to be associated with low GSH concentrations. In addition, aging is associated with an increased prevalence of cardiovascular disease, impaired glucose tolerance, and diabetes mellitus; the latter has also been shown to be accompanied by lower GSH concentrations. The mechanisms that could be responsible for a compromised GSH status include decreased synthesis and/or increased utilization relative to synthetic capacity. Ideally, one would like to measure in vivo rates of both GSH synthesis and utilization. Unfortunately, the multitude of pathways consuming GSH, as well as tissue variation, makes it impossible to have meaningful simultaneous measurements of utilization by all of the different pathways in the human. Hence, the focus of this proposal will be on GSH synthesis rates. We plan to test the hypotheses that 1) older men and women (age 60+ years) will have lower GSH synthesis rates and lower GSH levels compared to younger (<35 years) subjects and these differences will be exacerbated by diabetes mellitus in the old and 2) the provision of precursors for cysteine, the rate-limiting amino acid in GSH synthesis, will attenuate these differences. The specific aims are to determine: 1) Rates of GSH synthesis in younger and older groups of non-diabetic men and women using stable isotope tracer methodology, and GSH concentrations in plasma and erythrocytes of these volunteers. 2)The effect of diabetes mellitus on GSH synthesis rates and concentrations in older men and women. 3)The effect of GSH depletion by acetaminophen on rates of GSH synthesis in young and old non-diabetics. 4) The effect of GSH depletion by acetaminophen on rates of GSH synthesis in older non-diabetics and diabetics. 5) Whether acute administration of the cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTZ), will increase rates of GSH synthesis and GSH levels in young and old non-diabetic volunteers. 6) Whether acute administration of the cysteine precursor, OTZ, will
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increase rates of GSH synthesis and GSH levels 7 older nondiabetic and diabetic men and women. Data obtained in these in vivo studies will help to integrate in humans the diverse findings obtained in experiments conducted in animals and from in vitro cell culture systems and to improve our fundamental understanding of the effect of aging on GSH homeostasis in humans. It is hoped that the data will lay the groundwork for future studies examining the efficacy of nutritional supplements aimed at modulating an individual's GSH status and potentially ameliorating the deleterious effects of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL AND ACETAMINOPHEN HEPATOTOXICITY Principal Investigator & Institution: Sinclair, Jacqueline A.; Biochemistry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The overall goals of our research are to characterize the mechanism by which consumption of alcoholic beverages increases the risk of APAP hepatotoxicity. CYP2E1 is considered responsible for alcohol-mediated increases in APAP hepatotoxicity. However, our work suggests that CYP3A also has a role. We have recently found that alcohols also induce CYP1A2, another form of CYP that produces the reactive metabolite of APAP. In this proposal, using knockout mice, we will investigate the roles of CYP2E1, CYP3A and CYP1A2 in alcohol-mediated APAP hepatotoxicity. The widely consumed chemicals caffeine and theophylline enhance the activity of CYP3A, and thus have the potential to augment alcohol-mediated APAP hepatotoxicity if consumed simultaneously with APAP. Therefore it is important to ascertain whether these methylxanthines are additional risk factors in alcohol-mediated APAP hepatotoxicity. In this proposal, we will also investigate the effects of caffeine and theophylline on alcohol-mediated APAP hepatotoxicity in rodents. HYPOTHESES We hypothesize that CYP3A can have a major role in the enhancement of APAP hepatotoxicity by alcohols. The actual contribution of a CYP in alcohol-mediated APAP hepatotoxicity will depend on the relative amount of that CYP as well as its activity in the liver at the time of exposure to APAP and the dose of APAP. The SPECIFIC AIMS of this proposal are: 1. To investigate the relative roles of CYPs 3A, 2E1 and 1A2 in APAP hepatotoxicity caused by pretreatment with ethanol and isopentanol, using CYP and reporter gene knockout mice. 2. To investigate the effect of methylxanthines, which increase CYP3A activity but decrease CYP1A2, on alcohol-mediated APAP hepatotoxicity in wild-type and CYP1A2 knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1 Principal Investigator & Institution: Cederbaum, Arthur I.; Professor of Biochemistry; Pharmacology/Biological Chem; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 29-SEP-2003 Summary: (Adapted from the Investigator's Abstract) There is much current interest in the role of CYP2E1 in alcohol-induced liver injury. We propose to characterize CYP2E1and ethanol-mediated cytotoxicity in HepG2 cell models either transduced or transfected to express human CYP2E1. We have recently developed a new HepG2 cell line which over-expresses CYP2E1 at levels 5 to 10-fold greater than previously
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established cell lines. The CYP2E1 over-expressing E47 cells grow at a slower rate than control cells but remain viable. When GSH is depleted, marked toxicity is observed with the E47 cells but not control cells. Sp. Aim I is designed to characterize and evaluate mechanisms involved in this growth inhibition effect caused by over-expression of CYP2E1 and in the cytotoxic effect observed when GSH is depleted. The ability of antioxidants and iron chelators to prevent the growth inhibition and cytotoxicity, and the ability of iron and polyunsaturated fatty acids to exacerbate these effects will be determined. Impairment of mitochondrial function and development of oxidative stress will be studied. Whether injury is apoptotic in nature and the ability of bcl-2 to "rescue" the cells from CYP2E1-catalyzed toxicity will be evaluated. Calcium plays a critical role in cell injury produced by oxidative stress and hepatotoxins. Aim II will evaluate the ability of metabolites derived from CYP2E1 oxidation of ethanol and other substrates and CYP2E1-catalyzed formation of reactive oxygen species to activate Ca2+ channels in microsomes and promote release of Ca2+. The role of Ca2+ in toxicity exhibited by ethanol, PUFA or over-expressed CYP2E1 in HepG2 cells will be evaluated. Aim III will evaluate whether oxidative stress mediated by CYP2E1 itself or CYP2E1 interactions with ethanol, PUFA, acetaminophen activates the transcription factor NF-kB, and if so, whether the HepG2 cells can initially be protected against injury by upregulation of NFkB-activated genes. Special emphasis will be on cellular GSH levels. TNF-CYP2E1 interactions and induction of IL-8, a powerful chemoattractant will be evaluated. Selected experiments will be carried out with cultures containing hepatocytes isolated from chronic ethanol-fed rats and pair-fed controls to allow extrapolation of results with the HepG2 cells to normal hepatocytes. It is hoped that these studies will help to define the role of CYP2E1 and CYP2E1-derived reactive oxygen species in the hepatotoxic actions of ethanol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL, DYSFUNCTION
ACETAMINOPHEN,
AND
LIVER
SINUSOID
Principal Investigator & Institution: Mc Cuskey, Robert S.; Professor and Head; Cell Biology and Anatomy; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: Acute liver failure and death due to the ingestion of normally therapeutic doses of acetaminophen (APAP), Tylenol, is a serious clinical problem in chronic alcoholics. The toxic response to APAP is hallmarked by hemorrhagic centrilobular necrosis and towering levels of serum transaminases which are preceded by centrilobular microvascular injury and congestion. Little is known about the pathophysiology of this early microvascular lesion, which is suspected to be important in the progression of magnitude of the subsequent parenchymal injury. We propose to study this aspect of the toxic response of the liver to APAP and its potentiation by alcohol bringing. The later is a growing and serious problem, especially on college campuses, but is pathophysiology has received little experimental attention. Preliminary data strongly suggests that alcohol binge drinking significantly increases the susceptibility of the liver to injury by APAP. The hypotheses to be tested in mice are: (a) APAP elicits alterations in the hepatic microvascular in a dose dependent manner that precedes and potentiates parenchymal injury and that alcohol bringing increases the susceptibility of the liver to injury by APAP; (b) that sinusoidal endothelial cells (SEC) and their cytoskeleton are the principal sites of microvascular injury; and (c) that injury to SEC is related to changes in their intracellular levels of glutathione (GSH) and cytochrome P450-2E1 (CYP2E1) as well as mediators released from Kupffer cells and/or
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recruited inflammatory cells. High-resolution in vivo microscopy will be used to determine the dynamic spatial and temporal development of hepatic microvascular dysfunction. Light and electron microscopic examination of fixed specimens and isolated SEC will elucidate structural alterations that can not ve visualized in vivo. These will be correlated with changes in GSH, CYP2E1, pro-inflammatory cytokines, superoxide, nitric oxide in SEC, liver and plasma to gain clues to explain the responses observed microscopically. How inhibition of these mediators modifies the injury will further elucidate their role. The results should provide new information about the pathophysiology and mechanisms involved in the early microvascular injury elicited by overdoses of APAP associated with suicide attempts or therapeutic doses of APAP in abusers of alcohol and their contribution to the time course, progression, and magnitude of hepatic injury. A better knowledge of the hepatic pathophysiology of alcohol bringing also should result. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALTERED HEPATIC DISPOSITION OF ANIONIC DRUGSMECHANISMS Principal Investigator & Institution: Brouwer, Kim L.; Professor and Director of Graduate Studi; Drug Delivery & Disposition; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 30-JUN-2005 Summary: Altered hepatic disposition of anionic drugs secondary to drug interactions, chemical exposure, disease states or genetic variations has important therapeutic implications. Systemic exposure and duration of pharmacologic activity may be altered substantially by changes in hepatic translocation of drugs. Likewise, altered hepatic transport can influence systemic, hepatic, or intestinal toxicity. The long-term objective of this research program continues to be the development of a mechanistic understanding of how perturbations in hepatic transport influence overall hepatobiliary disposition of anionic drugs and derived metabolites. A multiexperimental approach utilizing in vivo, isolated perfused rat liver, and in vitro cellular systems will be employed to elucidate mechanisms of altered function of hepatic organic anion transport systems. The hypothesis that hepatic canalicular (Mrp2) and basolateral (Mrp3) transporters function in a coordinate fashion to modulate biliary excretion, intrahepatic concentrations and systemic exposure of anionic substrates will be tested. The utility of an in vitro model system to explore mechanisms of altered hepatobiliary transport, including fundamental aspects of transporter regulation and trafficking, and to predict functional consequences, will be evaluated. This model system represents an exciting tool for studying hepatobiliary drug disposition as it maintains hepatocyte polarity and bile canalicular function, allows direct access to the hepatocyte and adjacent biliary compartment, and minimized the use of experimental animals. Extension of this in vitro methodology to human hepatocytes may provide a novel approach to examine hepatic transport mechanisms and drug transport interaction in the human hepatobiliary system. A pilot study to validate a method of quantify biliary excretion in humans will be performed to evaluate in vitro/in vivo correlations. Elucidation of the mechanisms of hepatic organic anion transport, and knowledge of how xenobiotic interactions or physiologic variations alter these processes, is fundamental to understanding how the liver disposes of endogenous and exogenous compounds. This information will facilitate a priori predictions of hepatic xenobiotic/metabolite disposition in response to altered hepatic transport, and is prerequisite to exploiting hepatic transport processes to achieve desirable therapeutic
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endpoints. The merit of this work is realized when one considers the number of xenobiotics that undergo hepatic elimination, and the potential for alterations in hepatic transport of these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALGESIA OF SC-65872, OXYCODONE/ACETAMINOPHEN, OR IBUPR Principal Investigator & Institution: Brennan, Timothy J.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: This study is designed to compare the analgesic efficacy and safety of orally administered SC-65872, a novel compound that exhibits potent anti-inflammatory and analgesic activity via selective inhibition of one form of the enzyme cyclooxygenase, to oxycodone/acetaminophen, ibuprofen and placebo in patients with moderate to severe pain after general surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ANALGESIC CHALLENGES IN ASPIRIN SENSITIVE ASTHMATIC PATIENTS Principal Investigator & Institution: Stevenson, Donald D.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ANALGESIC USE AND THE RISK OF CHRONIC RENAL FAILURE Principal Investigator & Institution: Curhan, Gary C.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-AUG-1998; Project End 31-JUL-2004 Summary: Analgesic-associated nephropathy is potentially fatal and costly yet completely preventable as a cause of renal dysfunction. Retrospective studies have reported an increased risk of renal dysfunction associated with consumption of large amounts of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) but not aspirin. Since these analgesics are widely available and used, their association with renal dysfunction is particularly important. The primary objective of this study is to examine, prospectively, the association between chronic consumption of acetaminophen, aspirin and NSAIDs, and the risk of chronic renal dysfunction, defined as an increase in serum creatinine or a decrease in calculated creatinine clearance during the 5-year study period. From participants in two large female cohorts, the Nurses' Health Studies I and II (NHSI, NHSII), 3 groups of women will be identified, each comprised of 1150 participants (half from each cohort), who reported frequent use of acetaminophen, aspirin, or NSAIDs, and a fourth group of 1150 women who reported no use of these analgesics. Detailed information on dosage and duration of analgesic use will be obtained through supplementary questionnaires, to be mailed in the 01, 03, and 05 years, which have been shown to be reproducible. 4600 nurses will be enrolled at the outset and, after excluding women with prevalent renal disease and those who drop out, an expected 4000 will complete the study in the 05 year. The outcomes are: change in serum creatinine and calculated creatine clearance, measured at baseline and years 03
12
Acetaminophen
and 05 from all subjects. Mixed effects regression will be used to analyze the slope of renal function in the unexposed and exposed groups during the 5 year study period. For approximately 2000 subjects in NHSI, stored blood from 1989 will be used to perform the same analyses over a 13 year period. This study will provide: prospective data on change in renal function associated with chronic analgesic use; threshold levels of safe cumulative dose and duration of these analgesics; and population-based incidence rates and attributable risks of analgesic-associated chronic renal dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALGESICS INDIVIDUALS
AND
RESISTANCE
TRAINING
IN
OLDER
Principal Investigator & Institution: Trappe, Todd A.; Assistant Professor of Geriatrics and Ph; Geriatrics; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): We have shown that over-the-counter doses of the common analgesics ibuprofen and acetaminophen block the normal increase in skeletal muscle protein synthesis following resistance exercise. These two drugs are the most commonly used drugs by individuals that suffer from osteoarthritis, who number nearly 25 million in the United States. Many of these individuals are over the age of 65 y and are increasing their physical activity through resistance exercise as a result of a physician recommendation to help their arthritis or to improve their muscle strength, functional status, and overall health. Chronic consumption of acetaminophen or ibuprofen, or similar analgesic and anti-inflammatory drugs, may chronically inhibit skeletal muscle protein synthesis and the resultant hypertrophy and strength gains in strength training individuals. We propose to study two groups of older (65-80 y) women and men who have arthritis: 1) Those that have upper-body osteoarthritis (i.e., of the hand or shoulder), and 2) Those that have lower-body osteoarthritis (i.e., of the knee). This grouping will allow us to study individuals that need to take analgesic therapy and to separate the effects of the drugs on the exercise responses from the ability to perform the exercise, which may or may not be compromised in those individuals with osteoarthritis of the knee. We will examine the fractional rate of muscle protein synthesis (FSR), muscle hypertrophy (size) using magnetic resonance imaging and muscle fiber size, and muscle strength before and after four months of resistance exercise training of the lower body in an age-matched group that does not take any drug (control group), and upper- and lower-body arthritic groups that consume either acetaminophen (4 g.d-1) or ibuprofen (1.2 g.d-1) during the training period. We hypothesize that skeletal muscle FSR, size, and strength will be increased in the control group, while increases in these variables will be blunted in both the upper-body and lower-body arthritic groups that consume acetaminophen or ibuprofen. Dr. Trappe, a new investigator, and the co-investigators in the Department of Geriatrics and the Division of Rheumatology at UAMS have experience in all of the proposed methodologies. This investigation will provide important information for clinicians and older individuals with regard to expected benefits from physical activity during periods of analgesic and anti-inflammatory based therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIOXIDATIVE ROLE OF GPX1 IN VIVO OF TRANSGENIC MICE Principal Investigator & Institution: Lei, Xingen; Animal Science; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853
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Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2006 Summary: (provided by applicant): Cellular glutathione peroxidase (GPX1), a major selenium (Se)-containing protein in the body, has been widely considered an antioxidant enzyme. Most striking, we have found that although the enzyme protects against oxidative stress mediated by reactive oxygen species (ROS) in vivo and in vitro, knockout of GPX1 actually renders mouse hepatocytes highly resistant to apoptosis and protein nitration induced by 0.4 mM peroxynitnte (OONO-, PN), a potent reactive nitrogen species (RNS). Because this promoting role of GPX1 in the PN-induced oxidative stress is so fascinating, we propose to determine the underlying biochemical mechanism, signal pathway, and metabolic relevance. Our long-term goal is to elucidate the physiological function of GPX1 gene expression in Se nutrition and human health. We will conduct eight experiments to achieve three specific aims. First, we will use both ROS generators and scavengers as well as glutathione synthesis modulators to determine whether moderate elevation of intracellular ROS and glutathione duplicates the GPX1 knockout effect on the PN-induced oxidative stress in mouse hepatocytes. Second, we will use specific inhibitors to test whether the GPX1 action in these cells is signaled by the cytochrome c/caspase 3, poly(ADP-nbose) polymerase (PARP), and mitogen-activated protein kinase (MAPK) pathways. Last, we will find out if and how GPX1 promotes oxidative stress induced by endogenous PN generated from acetaminophen metabolism in mouse hepatocytes and liver. Key assays will be oxidative injuries including DNA fragmentation or strand breaks and protein nitrotyrosine formation, apoptotic signaling including cytochrome c release and activation of caspase 3, PARP, and MAPK, and cell death or histopathology. Our results will unveil a novel function of GPX1 and Se, and help define their dual role in coping with ROS and RNS. These findings may not only enhance our understanding of the mechanisms of Se in preventing cancer, viral infection and chronic diseases, but also lead to fundamental changes in the current theory and application of antioxidants, and shed new light on pathogeneses of many ROS/RNS-related diseases. Therefore, this research will make significant contribution to guiding the optimal use of Se and GPX1 mimic to improve the US public health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL SALICYLATE
PHARMACOLOGY OF
ACETAMINOPHEN
AND
Principal Investigator & Institution: Oates, John A.; Professor and Chairman; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: (provided by applicant) In contrast to the cyclooxygenase inhibitors in the nonsteroidal anti-inflammatory class, acetaminophen exerts a more narrow spectrum of pharmacologic effects, acting primarily as an antipyretic and an analgesic agent with much less effect on inflammation, the platelet, and the gastrointestinal tract. Acetaminophen is known to inhibit prostaglandin production in the central nervous system and endothelial cells. We have found that the inhibition of prostaglandin biosynthesis by acetaminophen in endothelial cells was more marked when these cells were stimulated with the pyrogen, IL-l alpha, which induces both cyclooxygenase-2 and PGE2 synthase in the endothelial cell, with a resultant increase in prostacyclin and even more marked increase in the biosynthesis of PGE2. In human studies we have found that endotoxin markedly increases prostacyclin biosynthesis. From these preliminary data we postulate that acetaminophen will inhibit the biosynthesis of the prostaglandin pyrogen, PGE2, and pyrexia induced by endotoxin, and will assess this in a study with
14
Acetaminophen
human volunteers. It is also hypothesized that during endotoxemia, acetaminophen will inhibit prostacyclin biosynthesis to a greater degree than in the control state. The effect of reducing production of this potent inhibitor of platelet aggregation on the enhanced activation of platelets in vivo during endotoxemia will be Sodium salicylate in high doses has anti-inflammatory properties. It is a weak inhibitor of purified cyclooxygenase in vitro, but has been shown to reduce prostaglandin biosynthesis in some cells. The mechanism of its antipyretic effect is unknown. We plan to determine whether an antipyretic dose of salicylate will inhibit prostaglandin biosynthesis in endotoxininduced pyrexia, and also to assess this in relationship to the doses that exert an antiinflammatory effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLON ACETAMINOPHEN
AND
LIVER
ANTICARCINOGENICITY
BY
Principal Investigator & Institution: Williams, Gary M.; Professor; Pathology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The overall objective of the proposed research is to examine the hypothesis that phenolic compounds can act as anticarcinogens at low levels by blocking the cellular effects of carcinogens that operate as reactive electrophiles. In testing this hypothesis, we will conduct a series of in vivo studies in rats with the widely used analgesic acetaminophen (APAP), which has demonstrated anticarcinogenic properties in colon. As model carcinogens in the rat, 3,2'-dimethyl-4aminobiphenyl (DMAB) and 2-amino-3-methyl-3H-imidazo [4,5-f]quinoline (IQ) will be used to produce a moderate level of initiation in rat colon as well as liver. We will establish the ability of low levels of APAP to inhibit the early carcinogen-induced effects that underlie initiation of colon and liver carcinogenesis, such as enhanced cell proliferation, decreased apoptosis and induction of preneoplastic lesions, and will study the mechanism(s) of this inhibition, focusing on blocking of intracellular reactivity of the carcinogens (i.e., adduct formation). These experiments will be pursued in three specific aims as follows: 1. Define low doses of the carcinogens 3,2'-dimethyl-4-aminobiphenyl (DMAB) and 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) that produce a moderate level of initiation in rat colon and liver to be studied for inhibition by low levels of APAP; 2. Establish the dose responses for inhibition of carcinogen-induced initiation by low levels of APAP against selected doses of carcinogens in order to determine conditions for mechanistic studies and 3. Determine whether low levels of APAP inhibit initiation by reduction of formation of IQ DNA adducts in order to gain insight into potential mechanisms of anticarcinogenicity. These experiments will provide the basis for future studies of prophylaxis against human carcinogens, such as aflatoxin B1. In addition, these experiments will provide support for the epidemiological observations of reduced cancer risk associated with the use of APAP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF NOVEL THERAPEUTICS FOR POSTSURGICAL PAIN Principal Investigator & Institution: Narducy, Kenneth W.; St Charles Pharmaceuticals 478 Broadway St New Orleans, La 70118 Timing: Fiscal Year 2002; Project Start 01-NOV-1998; Project End 29-FEB-2004
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Summary: Acetaminophen and NSAIDs have been used routinely for treatment of pain and/or fever. This dual action is sometimes contraindicated. In many instances, pain needs to be controlled without masking symptomatic fever (e.g., during the postoperative period). These drugs can cause hepatotoxicity, particularly after ingestion of large doses or from chronic use (especially when liver function has been compromised), which can lead to death. We are exploring a series of new and proprietary derivatives of acetaminophen that have good pharmacological potency and little hepatotoxic, nephrotoxic, or antipyretic effects. In preliminary studies, the initial compounds demonstrated high analgesic activity free from antipyretic activity and hepatotoxicity. In Phase I, we further characterized these initial compounds and several other analogs/derivatives and identified a lead candidate drug. We will further test and develop this drug in Phase II for treating postoperative pain and for other analgesic treatments where acetaminophen is contraindicated. We will also use a combination of in vitro and in vivo models to evaluate additional analogs and derivatives of the Phase I lead candidate drug. We will choose second-generation candidates based on efficacy, pharmacokinetic, and toxicity evaluations. PROPOSED COMMERCIAL APPLICATION: The market for pain relievers in the US is estimated to be approaching $6 billion. Acetaminophen (marketed under the name Tylenol(TM) and other brand names) represents about 48% of that market. Although widely used, acetaminophen is not without some serious side effects. There is a clear unmet medical need for pain relievers that are effective but have a better safety profile than acetaminophen. This research is directed at developing a pain reliever that is as effective as acetaminophen but with fewer side effects. This drug would be targeted at those patients most at risk from acetaminophen toxicity, particularly those who must take pain relievers on a chronic basis, and those with postoperative pain where masking of fever by acetaminophen could delay the diagnosis of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG INTERACTIONS Principal Investigator & Institution: Rettie, Allan E.; Professor and Chair; Medicinal Chemistry; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-1983; Project End 31-JUL-2008 Summary: (provided by applicant): Metabolically-based drug-drug interactions are a major cause of morbidity and mortality in the therapeutic treatment of disease. Although significant advances have been made in our understanding of the etiology of such adverse drug reactions, quantitative prediction of these events at early stages of drug development and clinical use remains elusive. This Program Project Grant focuses on understanding the in vitro to in vivo relationships for drug-drug interactions involving the human cytochrome P450 family of enzymes and drug transporters. In the current proposal, we will investigate several emerging factors that complicate our ability to accurately predict changes in drug metabolizing enzyme and drug transporter activity that result from the co-administration of multiple interacting species; (i) nonhyperbolic kinetics and cooperative ligand binding to human P450s, (ii) sequential oxidative metabolism and the formation of metabolic-intermediate (MI) complexes, (iii) the variable contribution made by Type II binding to inhibitor Ki, (iv) the role(s) of drug transporters such as the human OCTs, MDRs and MRPs, and (v) the interplay of drugmetabolizing enzymes and drug transporters in drug interactions associated with induction mechanisms. In Project 1 we will synthesize novel high affinity inhibitors for human CYP2C enzymes and combine this with site-directed mutagenesis studies to enable construction of discriminating computational and structural models for the
16
Acetaminophen
prediction of inhibitor Ki. In Project 2, we will explore the mechanistic basis for 'allosteric' kinetic behavior with CYP3A4, towards a variety of ligands including caffeine, acetaminophen, pyrene and hypericin using fluorescence and NMR-based approaches. In Project 3, we will explore reasons for the discrepancy between in vivo and in vitro Kis for the test compounds, itraconazole and fluvoxamine and develop new kinetic models for sequential metabolism and MI complex formation with macrolides and antidepressants. In Project 4 we will determine the molecular and genetic factors that influence, both in vivo and in vitro, the magnitude and spectrum of human P450 enzymes and drug transporters induced by the anti-HIV protease inhibitors, nelfinavir and ritonavir. Collectively, these studies should provide new conceptual and practical tools to achieve quantitative predictions of drug-drug interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG METABOLISM AND CHRONIC LIVER DISEASE Principal Investigator & Institution: Branch, Robert A.; Professor/Director; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): This is a resubmission of a proposal whose goal is to use pharmacogenetic principles to better understand the influence of liver disease associated with hepatitis C on drug disposition and develop new tools to evaluate hepatic function. We propose to address the following specific hypotheses: In Specific Aim 1: Hepatitis C influences the clearance of drugs that undergo metabolism in comparison to matched controls. Furthermore, the extent of change in clearance is different for drugs that are metabolized by different drug metabolizing enzymes and is associated with the severity of the liver disease. Specific Aim 2: Selective decreases in drug metabolism in patients with hepatitis C without hepatic decompensation is associated with enzyme specific down-regulation of hepatic expression of mRNA for that enzyme and increased circulating levels of the cytokines, Interleukin-6 and Tumor Necrosis Factor- ?. Specific Aim 3: The measurement of activity of multiple drug metabolizing enzymes can be interpreted in the context of a sequential, progressive model of hepatic dysfunction to provide an integrated assessment of hepatic function and prognosis in patients with hepatitis C. We propose to study patients with hepatitis C (n= 112) associated with chronic persistent hepatitis, chronic active hepatitis and cirrhosis with or without hepatic decompensation and age, sex matched controls (n=48) on two occasions. Each study subject will participate in three pharmacokinetic (PK) studies that uses drugs selected as probes of substrates metabolized predominantly or exclusively by an individual drug metabolizing enzyme. Part 1: A cocktail to include: caffeine (CYP1A2), flurbiprofen (CYP2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and dapsone (acetylation). Part 2: Semisimultaneous oral:intravenous administration with midazolam to measure intestinal and hepatic contributions to CYP3A metabolism and Part 3: oral administration of acetaminophen (UGT1A6) simultaneously with intravenous morphine (UGT2B7). When feasible, liver tissue obtained at the time of diagnostic liver biopsy as part of routine patient care will have concentrations of mRNA for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, UGT1A6 and UGT2B7 measured. Patients with hepatitis C-associated liver disease will be followed at 6 monthly intervals until liver transplantation, death or duration of funding. The study will be repeated either after a change in clinical status or at 2 years in patients with liver disease and after one or 12 months in control subjects. Collectively, these studies will provide a consolidated base of information within the same cohort of patients with hepatitis C and normal subjects
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to better understand the influence of hepatitis C-associated live disease on drug metabolizing enzymes. This information has potential to create new integrated indices to evaluate hepatic function and prognosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF CIRRHOSIS AND SHUNTS ON DRUG DISPOSITION Principal Investigator & Institution: Gorski, J. Christopher.; Associate Professor of Medicine; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): It is well established that hepatic cirrhosis results in reduced clearance of drugs that are highly metabolized and an enhanced sensitivity to the pharmacological and adverse actions of drugs. Chronic alcohol consumption and hepatitis C are the two most common causes of cirrhosis in the United States with an incidence of 3.1 per 1000 people. The development of portal hypertension is the primary mechanism behind several major complications of cirrhosis such as bleeding from gastroesophageal varices, hepatic encephalopathy, and ascites. Transjugular intrahepatic portosystemic shunts (TIPS) and other surgical shunts are performed to manage these complications of portal hypertension. We have demonstrated that in addition to a reduction in hepatic clearance, cirrhotic patients with TIPS experience an increase in intestinal availability of midazolam, a selective cytochrome P450 3A (CYP3A) substrate. This increased bioavailability primarily reflects a functional lack of intestinal wall firstpass metabolism relative to cirrhotics without TIPS and healthy volunteers. The mechanism for this lack of intestinal wall metabolism is unknown. We propose to characterize the mechanism and consequences of this loss of intestinal wall CYP3A activity in cirrhotics with TIPS by directly examining the CYP3A protein and mRNA levels, intestinal permeability, and in vivo hepatic and intestinal CYP3A activity before, immediately after, and I month after TIPS placement. Cirrhotic patients with TIPS, and potentially other types of portosystemic shunts, are expected to be at risk for excessive pharmacological effects or suffer from an increased incidence of adverse reactions following CYP3A substrate administration. We will examine the susceptibility of these individuals to adverse drug reactions and drug-drug interaction by examining the ability of erythromycin to prolong the QT interval and clarithromycin to inhibit metabolism of buspirone, a CYP3A substrate. Finally, the expression of other enzymes such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs) and pglycoprotein may also be altered in cirrhosis. We will characterize the changes in these enzymes using the partial clearance of acetaminophen to glucuronide (UGT) and sulfate (SULT) conjugates and the disposition of fexofenadine in cirrhotics with and without TIPS and healthy volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFICACY OF ACUPUNCTURE WITH PT FOR KNEE OSTEOARTHRITIS Principal Investigator & Institution: Farrar, John T.; Senior Scholar; Biostatistics and Epidemiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 31-MAR-2006 Summary: Acupuncture is an ancient Chinese technique of using a fine needle to stimulate points along theoretical meridians of energy to correct imbalances thought to be responsible for specific disease states. In the United States, acupuncture is often used
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Acetaminophen
for the treatment of painful conditions. The 1997 NIH Consensus Conference concluded that there was adequate evidence of efficacy in an acute dental pain model and in nausea. In chronic pain, most studies were too small, poorly designed, poorly executed, or improperly controlled to adequately demonstrate that needle acupuncture worked better than sham acupuncture, placebo, standard medical therapy, or even no treatment. Osteoarthritis (OA) of the knee has been proposed as a good model to test the efficacy of acupuncture in a chronic pain condition because it is an extremely common, well defined, and disabling condition with well established outcome measures for symptoms and functional status. There is clinical trial evidence of efficacy for the standard treatments of acetaminophen and NSAIDs, and exercise physical therapy (EPT), which is usually added when the patient develops functional limitations. One high quality study of acupuncture for knee OA, demonstrated moderate benefit in an unblinded comparison to a usual care control group. As such, a major question remains about whether acupuncture, used in addition to exercise therapy, will provide a clinically meaningful improvement in pain and function. Since pain can be the primary limiting factor in improved exercise capacity, if acupuncture has any efficacy in reducing the pain of knee OA, then the combination with an EPT program should be substantially more effective than EPT alone. Another major concern is that the effect of the acupuncture may be predominantly mediated by non- specific placebo effects rather than the specific effects of the placement of a needle. Another important component of this proposal is our use of a validated blinded placebo needle instead of sham acupuncture points. Therefore, the primary goal of this proposal is to use a properly designed randomized blinded clinical trial, using American College of Rheumatology (ACR) criteria and Food and Drug Administration (FDA) recommended outcome measures, to determine whether the addition of acupuncture to standard EPT provides an overall clinically important benefit to patients with symptomatic knee OA compared to placebo acupuncture. As a secondary goal, we will use the clinical trial data to develop prognostic and etiologic models for the patients that are most likely to respond to acupuncture. If a clinically important benefit for acupuncture is found, a broader application of this technique would be justified. However, if the results are negative, then the addition of acupuncture to EPT should be generally curtailed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOOD RESTRICTION ON ACETAMINOPHEN METABOLISM & DISPOSITION 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: The purpose of this study is to determine the effects of decreased food intake by obese patients on the elimination of acetaminophen from blood and on the acetaminophen metabolite ratio in urine. The theoretical basis of the study is the known qualitative and quantitative pathways of normal acetaminophen degradation and the evidence that it is the oxidative minor metabolite which, if not combined with glutathione, is toxic to the liver and, secondarily, to the kidney. It is known that fasting results in depletion of glutathione and, to a lesser extent, of glucuronic acid. The net result would be a shunting of more acetaminophen to the toxic oxidative pathway. The study proposes to restrict dietary intake in two groups, one to 1,000 kcal/day for 2 weeks and one to 500 kcal/day for 5 days. A 2 gm dose of acetaminophen will be used as a probe. It is expected that there will be lower drug removal from blood and a shift in
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urinary metbolites toward mercaptide. This will be correlated with plasma glutathione, as 60% of this is derived from liver. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHENOTYPES
GLUCURONIDATION
IN
HUMANS--GENOTYPES
AND
Principal Investigator & Institution: Lampe, Johanna W.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Glucuronidation is an important detoxification process that plays a critical rote in the defense against chemical induced carcinogenesis. drug toxicities, and hormonal imbalances. UDP-glucuronosyltransferases (UGTs) catalyze the transfer of the glucuronyl group from uridine 5'-disphosphoglucuronic acid to endogenous molecules, such as bilirubin and steroid hormones, and exogenous substrates, such as drugs, plant-food Constituents, environmental pollutants, and carcinogens. The resulting glucuronyl products are more polar, generally water-soluble, less toxic, and more easily excreted than the substrate molecules. Polymorphisms in several UGT isoforms influence glucuronidation of xenobiotic compounds, as well as bile acids and some steroid hormones. The opposite reaction, the hydrolysis of such glucuronide moieties by human beta-glucuronidase (f3-G) can restore biologic activity of xenobiotics and steroid hormones. Thus, the impact of beta-G as part of the glucuronidation cycle should also be considered. We postulate that the induction of UGTs and the inhibition of beta-G are plausible mechanisms by which a diet high in vegetables and fruit (V&F) may reduce risk of various diseases. We propose to examine the effects of V&F consumption on UGT and beta-G activities, considering the potential interaction with genetic polymorphisms in several relevant UGTs. The specific aims of this proposal are: 1) To determine whether UGT activity, as measured by acetaminophen and aspirin glucuronide formation and serum bilirubin concentrations, differs by UGT genotypes for the following isozyme polymorphisms: UGTIAI*28, UGT/A6*2, and UGT2B15(D85Y); 2) To measure the effect of feeding specific V&F under controlled dietary conditions on UGT and beta-G activity; and 3) To determine whether the effects of these plant foods on UGT activity differ by UGTgenotypes (UGTJA1*28, UGTIA6*2, UGT2BI5(D85Y)). The project will be implemented in two parts: 1) a cross-sectional study and 2) a feeding study. For the cross-sectional study, we will recruit 300 non-smokers, aged 20-40 years, and who are not taking any medication. We will genotype them for UGTIAI*28, (UGTIA6*2, and UGT2B15(D85Y), measure acetaminophen, aspirin metabolite, and bilirubin conjugation, and serum beta-G activity, and assess diet using a food frequency questionnaire and 3-day food records. For the feeding study, we will recruit a subset of the 300 (30 men and 30 women), based on their UGT genotypes, to take part in two, 14-day feeding periods. We will examine the effect of a high-V&F diet compared to a basal (low-phytochemical) diet on UGT and beta-G activities. The randomized cross-over design will allow us to test efficiently for diet effects within individuals, as well as for gene-by-diet and sex-by-diet interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCURONYL TRANSFERASE ACTIVITY IN THE FETAL PRIMATE Principal Investigator & Institution: Garland, Marianne; Assistant Professor; Pediatrics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2005
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Acetaminophen
Summary: A broad pharmocipia of drugs are used in pregnancy. Despite this, our knowledge of the disposition of drug to the fetus and how the fetus metabolizes various drugs is limited. Glucuronyltransferase, a common phase II conjugation system, is down regulated in the fetus and undergoes induction near birth. Despite the limited activity of this enzyme in utero, we have shown that fetal glucuronidation of drugs can have significant effects on fetal concentration of both drugs and their metabolites in the fetus. Drug concentrations are diminished and metabolite concentrations can exceed those in the mother. Furthermore. premature induction of these enzymes could lead to more pronounced effects. To predict the likely effect a drug will have on the fetus, pharmacokinetic models are required to estimate fetal drug and metabolite concentrations. Using glucuronyltransferase as a model, the goal of this proposal, is to establish the role of fetal metabolism in overall maternal-fetal pharmacokinetics. Our overall hypothesis is that fetal metabolism accounts for a significant amount of the observed nonplacental clearance of drug from the fetus. In addition, measures of glucuronyltransferase expression during fetal life will predict the observable changes in fetal drug and metabolite concentrations. We propose to test these hypotheses by a series of experiments in the fetal baboon. A novel pharmacokinetic approach to the quantification of the rate of formation of glucuronide metabolites in the fetal baboon will be combined with biochemical assays of glucuronyltransferase activity and quantitative measures of expressed protein (protein immunoanalysis and steady-state mRNA) in fetal tissues. We will quantify the rate of glucuronide formation of buprenorphine, imipramine, acetominophen, and morphine in the fetal baboon across late gestation and correlate this with biochemical measures of enzyme-activity. We will quantify the change in metabolism following exposure to phenobarbital and dexamethasone, known inducers of glucuronyltransferase, and then quantify the effect this has on steady-state fetal-to-maternal ratios following maternal drug administration. In conjunction with recent advances in pharmacologic therapy for pregnant women, there is a pressing need for developing pharmacokinetic models which reliably define drug levels in the fetus. The long-term goal of this research is to reverse a trend which left the fetus as a therapeutic orphan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTAMATE-L-CYSTEINE LIGASE EXPRESSION AND LIVER INJURY Principal Investigator & Institution: Kavanagh, Terrance J.; Environmental Health; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Oxidative stress is involved the pathophysiology of a large number of diseases. This stress originates not only from normal aerobic metabolism, but also from the metabolism of foreign compounds, and as a direct result of the release of reactive oxygen species by certain cell types. Organisms have evolved antioxidant defenses against oxidative insults, which include antioxidant enzymes and through the consumption of antioxidant compounds. A very important enzyme involved in antioxidant defense is glutamate-cysteine ligase (GCL), the rate limiting enzyme for the synthesis of the cellular antioxidant glutathione (GSH). The primary goal of this project will be to investigate the role of GCL in defense against substances and conditions which induce oxidative damage to the liver. We propose to characterize a transgenic mouse model of GCL overexpression, and to assess the effects of modulating GCL expression on susceptibility to oxidant-induced damage to the liver. We propose to use three agents known to cause oxidative liver injury, namely acetaminophen, carbon
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tetrachioride, and tumor necrosis factor-alpha. Transgenic and wild-type (normal) littermates will be exposed to non-lethal doses of these agents, and sacrificed from 6 to 48 hours later. Liver tissue will be excised and examined for signs of oxidative damage, cellular necrosis and apoptosis, and biochemical and cellular measures of cell viability and function will be made. Such information will be useful in determining the functional significance of GCL in defense against reactive oxygen species and xenobiotics which induce oxidative stress, and lead to a better understanding of the significance of variable GCL expression in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATOXICITY CLINCAL RESEARCH NETWORK Principal Investigator & Institution: Watkins, Paul B.; Professor of Medicine; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): This proposal represents an institutional response from the University of North Carolina at Chapel Hill (UNC) to become a Clinical Center under the RFA (DK-02-033) recently announced by the National Institutes of Health entitled: HEPATOTOXICITY CLINICAL RESEARCH NETWORK (HCRN). During year one, we will work with the Steering Committee to craft a standardized definition and, we believe, specific sub-definitions, of liver injury due to drugs, toxins, and complementary-alternative medicines (DILl). In addition, we will help develop and validate a diagnostic instrument for DILl. Year one will also be devoted to the development of protocols that will be HIPAA compliant, ethical, and have the highest likelihood for success in answering important questions concerning DILl. We propose a collaboration with researchers at the NIEHS that employs state-of-the-art technology to define the molecular events involved in acetaminophen toxicity. We also propose a second protocol that will define the natural history of DILl. The strengths of our proposal are: a) The location of our program within the UNC General Clinical Research Center (GCRC) which will allow efficiency through collaboration with existing GCRC personnel who have the demonstrated competence, experience, and infrastructure necessary for success. The GCRC will also serve as the centralized site for studies involving genotype/phenotype correlations, and we propose two such protocols, b) Cooperative understandings with the other two major academic medical centers in our region of the U.S. (Duke University and Medical College of Virginia), c) An extensive network of collaborating physicians, both gastroenterologists and primary care physicians, throughout the state facilitated by the UNC managed Area Health Education Centers (AHEC), d) Unique access to the state Medicaid database and evolving Emergency Department Network that will provide near real time access to HIPAA compliant patient data, e) Utilization of the traveling nurse team established by a coinvestigator to enroll research subjects and to obtain biological specimens from anywhere within our state, f) Access to large banks of DNA that will facilitate gene association studies by providing controls, g) An investigative team that is lead by both a senior investigator who has extensive experience in both the clinical and research aspects of DILl and a junior investigator who has targeted DILl as the focus for a K23 award. The team has extensive experience in all aspects of multicenter clinical trials including data collection, regulatory issues, and productive collaboration across institutions. We anticipate that our proposed infrastructure will allow successful identification and enrollment of patients experiencing severe DILl within the midAtlantic region of the country.
22
Acetaminophen
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOME CARE MANAGEMENT OF PEDIATRIC PAIN Principal Investigator & Institution: Sutters, Kimberly A.; Physiological Nursing; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 29-FEB-2004 Summary: The pediatric surgery outpatient population has grown extensively in recent years. Tonsillectomy, one of the most prevalent ambulatory surgeries in children, has been associated with a substantial degree of postoperative morbidity, with inadequate pain control cited as a major concern. Therefore, this randomized clinical trial will compare the effectiveness of a structured pain management program (i.e. that combines routine parent postoperative education, with around the clock (ATC) dosing of analgesics and nurse coaching, that is targeted at decreasing barriers to effective pain control in the home), with either standard care (i.e. routine parent postoperative education) and "as needed" analgesic dosing, or standard care and ATC dosing. Patients (N = 300) will be recruited from a large ambulatory surgery program and will be randomized to one of three treatment groups. Parents in the standard care groups will receive routine postoperative education and will be told to administer pain medication to their children every 4 hours "as needed" (Group A), or every 4 hours ATC (Group B). Parents in the structured pain management group (Group C) will receive and educational session that includes standard postoperative instructions and pain management education targeted at increasing knowledge and decreasing barriers to effective pain management as part of a coaching intervention, and will told to administer pain medication every four hours ATC. Parents in all three groups will receive follow-up phone calls on days 1 and 2 following surgery. In the standard care groups, the purpose of the phone calls will be to ascertain level of adherence with completion of the daily logs. Parents in the structured pain management group will receive coaching during the phone calls to include review of pain scores, child adherence to taking pain medicine, strategies for pain medication administration (as indicated), rationale for ATC dosing and instruction for ATC dosing, and potential side effects. Patients will be followed for three days and nights following tonsillectomy and parents will complete diaries in the morning and in the evening. The major outcome variables for this study are: pain intensity scores with and without swallowing, analgesic consumption, oral intake of fluids, negative behaviors and side effects. Patients and parents in all pain management groups will have and end of study interview to describe their experiences with the program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYDROXYCHLOROQUINE OR ACETAMINOPHEN IN NODAL ARTHRITIS Principal Investigator & Institution: Weisman, Michael H.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IATRONGENIC CAUSES OF CANCER Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033
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Timing: Fiscal Year 2002; Project Start 01-APR-1979; Project End 31-JAN-2004 Summary: This proposal requests continued support for a Program Project Grant (PPG) to conduct epidemiologic and biostatistical research on iatrogenic causes of cancer by investigators at the Kenneth Norris Jr. (University of Southern California) Comprehensive Cancer Center. This PPG is currently in its 16th year of continuous funding. The professional staff of this Program consists of 11 epidemiologists and statisticians with major research interests in iatrogenic exposures and cancer. The Scientific Program of the current application consists of 3 case-control studies. The successful conduct of these 3 projects depends on 5 core resources. The 4 projects include the following: (1) A continuation of an ongoing case-control study of the relationship of hormone replacement therapy and breast cancer risk in postmenopausal women. An expanded study will allow more detailed and precise evaluation of duration and latency effects, the evaluation of interactions and adequate adjustment for confounding factors; (2) A continuation of an ongoing case- control study of analgesics and diuretics and renal cell carcinoma. Preliminary results suggest that acetaminophen is associated with a greater increment in risk than aspirin, but the strong correlation between different formulations requires larger sample sizes to determine independent effects; and A continuation of an ongoing case-control study of diagnostic radiation and acute myelogenous leukemia. Preliminary data suggest a dose response relationship between trunk x-rays and risk but results are not statistically significant. The major core resource for this PPG is the Cancer Surveillance Program, a rapid ascertainment population-based tumor registry. Other core resources include a Medical Record Retrieval Core for validating self-reported prescription medications, diagnostic and therapeutic radiation, a Control Identification Core for identifying neighborhood controls for case-control studies, a Statistical Core for developing strategies for analyzing the types of studies described above and an Administrative Core for overseeing the scientific direction of the PPG and handling its fiscal administration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVED LIVER FUNCTION AND REGENERATION WITH A20 Principal Investigator & Institution: Ferran, Christiane; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Necrosis and apoptosis of hepatocytes are critical pathologic features associated with liver injury. Hepatocyte apoptosis is a feature of viral hepatitis, ischemic liver injury, sepsis, cholestasis, and a result of exposure to hepatotoxic substances such as ethanol, acetaminophen and cytostatic drugs. Massive hepatocyte apoptosis and necrosis result in fulminant hepatic failure (FHF). Only 14% of patients diagnosed with FHF recover with medical therapy. Orthotopic liver transplantation (OLT) has dramatically improved the fate of these patients (49% undergo OLT), yet 37% die while awaiting OLT. This gloomy picture is balanced by the unique capacity of the liver to regenerate. Hepatocyte replication leads to a full recovery of liver function and mass 1-2 weeks following surgical, viral or chemical hepatic loss. We propose that protecting hepatocytes from apoptosis and promoting their proliferation are two strategies that could beneficially impact FHF. Our preliminary data demonstrate that A20 promotes hepatocyte proliferation and is anti-apoptotic. A20 is part of the physiologic response of hepatocytes to injury. A20 is upregulated in hepatocytes by pro-inflammatory stimuli including TNF and LPS and functions to protect from TNF mediated apoptosis. Gene transfer of A20 to mice livers protects from lethality in the galactosamine and LPS (D-gal/LPS) model of toxic FHF. Adenovirus
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Acetaminophen
mediated expression of A20 in livers of BALB/c mice yields an 89% survival rate following administration of D-gal/LPS as compared to 15-20% in control mice. Mice expressing A20 maintain normal liver function as assessed by prothrombin time while controls suffer from a severe bleeding diathesis. Expression of A20 in the liver protects from lethality associated with a subtotal (87%) liver resection (LR). In this model, resection of 87% of the liver mass results in 100% lethality. In contrast, >60% of mice expressing A20 survive the 87% LR and demonstrate increased regenerative capacity as assessed by the number of PCNA (proliferating cell nuclear antigen) positive nuclei in the liver. These results qualify A20 as a critical gene involved in accelerating liver regeneration and promoting hepatocyte survival and function, even when facing extreme metabolic demands. These encouraging results prompted the submission of this proposal. Our specific aims are i) to dissect, in vitro, the molecular basis of the (1) antiapoptotic and (2) pro-proliferative function of A20 in hepatocytes and ii) to confirm that liver directed gene therapy using A20 will beneficially impact upon toxic, FAS-mediated and surgical experimental models of FHF. From a basic science standpoint, the in vitro work proposed will address the effect of A20 upon transcription factors and expression of genes involved in apoptosis, activation and proliferation of hepatocytes. This should unveil many unknowns in our understanding of hepatocyte biology and could lead to the discovery of novel therapeutic targets. From a therapeutic standpoint, validation of the beneficial effect of A20 in the murine in vivo models of FHF should set the basis for extending this approach to models of FHF in non human primates and potentially to clinical applications. The generation of novel safer and tissue specific viral vectors for gene transfer and the development of non-viral means of protein delivery to cells will facilitate clinical translation of A20 based therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERACTION OF ASPIRIN W IBUPROFEN, ACETAMINOPHEN OR ROF Principal Investigator & Institution: Fitzgerald, Garret A.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTION OF MIDAZOLAM AND ACETAMINOPHEN Principal Investigator & Institution: Feierman, Dennis E.; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: KUPFFER CELLS AND CHEMICAL TOXICITY Principal Investigator & Institution: Laskin, Debra L.; Professor; Pharmacology and Toxicology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 01-DEC-1984; Project End 30-APR-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LACTATE TRANSPORT & METABOLISM IN DOG LIVER Principal Investigator & Institution: Schwab, Andreas; Associate Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The appropriate model contains processes for influx into and efflux from both red blood cells and hepatocytes, as well as hepatocellular sequestration; however, in this case, part of the tracer emerges as labelled bicarbonate formed by the action of pyruvate dehydrogenase, whereas a presumably smaller part is incorporated into other metabolites by the action of pyruvate carboxylase. The model thus incorporates the formation of labelled bicarbonate as a metabolic product. The behavior of bicarbonate in the liver has previously been investigated using the multiple indicator dilution technique. Preliminary evaluation of the data showed that a substantial proportion of blood lactate is carried within red cells and therefore less readily available for hepatic uptake. The situation is similar to that for acetaminophen and will be treated in the same fashion. New experiments were therefore recently performed where lactate was injected in plasma alone (no red cells); the hematocrit in the bolus was re-established by simultaneously injecting blood where the hematocrit was increased by adding 51Crlabelled red cells (non-pre-equilibrated case), as previously done with thiourea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF ACETAMINOPHEN NEPHROTOXICITY Principal Investigator & Institution: Tarloff, Joan B.; Professor; Pharmaceutical Sciences; University of the Sciences Philadelphia in Philadelphia Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): Acetaminophen (APAP) is a commonly used analgesic agent that has been associated with acute liver and kidney damage when taken in overdoses. APAP or its nephrotoxic metabolite, para-aminophenol (PAP), may be responsible for the kidney damage. APAP-induced kidney damage has not been well investigated and the mechanisms responsible for injury have not been identified. The present proposal is designed to test the hypothesis that cell death due to APAP or PAP, regardless of the outcome, is initiated by apoptosis. Cell death is thought to occur by one of two processes, oncosis (necrosis) or apoptosis. Chemical-induced cytotoxicity has been considered to represent cell death by oncosis, but recent evidence suggests that low concentrations of chemicals may activate apoptotic pathways that allow deletion of sublethally injured cells. The current proposal will test the involvement of oncotic and apoptotic pathways in APAP and PAP-induced cytotoxicity by addressing the following specific aims: (1) examination of the time course and dose-dependence of DNA damage in vivo following administration of APAP and PAP, (2) examination of the time course and concentration-dependence of the appearance of apoptotic markers in vitro following incubation of LLC-PK1 cells with APAP or PAP, (3) examination of cytochrome c release from mitochondria in LLC-PK1 cells following incubation with APAP or PAP, and (4) determination of reactive oxygen intermediate (ROI) formation in LLC-PK1 cells following incubation with APAP or PAP. Evidence documenting apoptosis in vivo will be obtained by examining tissue collected from rats receiving nontoxic and toxic doses of APAP and PAP for DNA damage. Evidence documenting oncosis and apoptosis in vitro will be obtained by examining markers for both pathways in LLC-PK1 cells incubated with various concentrations of APAP and PAP. Mitochondria represent a target for APAP and PAP and mitochondrial damage may cause cytochrome c release from the inner mitochondrial membrane. Cytochrome c
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Acetaminophen
release will be investigated by incubating LLC-PK1 cells with concentrations of APAP and PAP shown to cause apoptosis. Cytosol and mitochondrial proteins will be separated by polyacrylamide gel electrophoresis and Western blotting for cytochrome c. ROI formation will be assessed using specific dyes that respond to these chemical intermediates. The results of these studies will shed important insight into mechanisms of cytotoxicity following exposure to APAP and PAP and into the relationship between apoptosis and oncosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ALTERED VECTORAL HEPATIC EXCRETION Principal Investigator & Institution: Slitt, Angela L.; Pharm/Toxicology/Therapeutics; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 01-SEP-2002 Summary: (provided by applicant): Understanding drug absorption, distribution, metabolism, and excretion (ADME) is essential for the development of safe, effective drug therapies. Moreover, understanding mechanisms by which drug-drug interactions affect drug ADME is also critical for identifying potential toxicities or side effects of pharmaceutical preparations. Specifically, this work seeks to relate the effects of microsomal inducers on hepatic excretion of drug conjugates to regulation of hepatic drug transporters responsible for the excretion of drug conjugates that result from phase I and II metabolism. This work will determine whether alteration in the vectoral route of excretion of acetaminophen (APAP) metabolites from hepatobiliary to hepatovascular by pretreatment with Phenobarbital-type microsomal inducers is due to changes in hepatic levels of the organic anion transporters mrp2 and mrp3. Therefore, specific aims 1 and 2 will determine whether hepatic levels/and or distribution of mrp2 and/or mrp3 is altered following treatment with constitutive active receptor (CAR) inducers and if these changes correlate with increased excretion of APAP-glucuronide, APAP-sulfate, and APAP-GSH from the liver into the blood. Next, specific aim3 will determine whether APAP metabolites are substrates for mrp2 and mrp3 using membrane vesicles prepared from Sf9 cells that heterologously express mrp2 or mrp3. Lastly, specific aim 3 will determine whether PB increases mrp3 mRNA through nuclear translocation of CAR and activation of a putative PB response element in the promoter region for rat mrp3. These studies will elucidate mechanisms that control hepatic transport and excretion of pharmaceuticals and will aid in the development of safer more biologically effective drug preparations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM DYSFUNCTION
OF
OPIATE
INDUCED
AUDIOVESTIBULAR
Principal Investigator & Institution: Ishiyama, Gail P.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The focus of this project will be the cellular and molecular mechanism mediating opiate-induced deafness and vestibular dysfunction. Profound bilateral deafness requiring cochlear implantation secondary to chronic high dose use of acetaminophen/hydrocodone has been reported by our Neurotology Clinic. Heroin and propoxyphene have also been associated with profound deafness and vestibular dysfunction. These experiments will test the hypotheses that: 1) There is a differential expression of opioid receptor mRNA in the rat and human auditory and
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vestibular periphery. 2) There is conservation of mRNA opioid receptor expression between rodent and human. 3) There is a higher degree of opioid receptor expression in the auditory than vestibular periphery. 4) NMDA and opioid receptors colocalize within the inner cochlear and type I vestibular hair cell. 5) Activation of opioid receptors in the inner ear will induce similar changes in cellular signaling pathways as activation in the central nervous system. 6) Chronic opiates induce opioid receptor mediated supersensitivity state, characterized by increased activation of adenylate cyclase, cAMPresponse element binding protein (CREB), mitogen- activated kinase (MAP kinase), and Akt (a serine/threonine protein kinase). In order to accomplish these objectives, inner ear tissues will be used for reverse-transcription-polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochernistry, morphological studies, and biochemical assays in both in vitro and in vivo models of acute and chronic opiate use. Information gained during the five year period will also provide basic science data relevant to the normal function of opioid signaling in the audiovestibular periphery. The mentored clinical scientist development award (MCSDA) is critical for the principal investigator to master the molecular and cellular biological techniques needed to establish herself as an academic neurotologist as it allows protected and mentored time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF CYTOCHROME P450 ALLOSTERY Principal Investigator & Institution: Atkins, William M.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Many drug-drug interactions are metabolic in origin, resulting from the activation or inhibition of Cytochrome P450 (CYP)-dependent drug clearance. A potential contribution to CYP-dependent drug interactions is the poorly characterized allostery that is widely observed in vitro, and also in vivo. This allostery includes nonhyperbolic steady state kinetic profiles for individual substrates (homotropic allostery), as well as alterations in the kinetic profiles of one drug by a second (heterotropic allostery). The molecular mechanisms leading to allostery are not defined, although several contrasting models have been proposed and include multiple ligand binding within a single fluid active site, multiple ligand binding within discrete subsites of this large active site, and ligand-dependent persistent protein conformational equilibria. Here, non-steady state kinetic methods will be exploited to challenge these models and to understand CYP allostery in the context of existing structural models for CYP3A4 and CYP2C9. The specific aims are: 1) to determine whether the elementary steps of ligand binding, ligand-dependent ferric spin state equilibrium, or ligand-dependent changes in gross protein conformation are differentially allosteric for the homotropic effects of testosterone, pyrene, and hypericin with CYP3A4; 2) to determine by paramagnetically shifted 1H-NMR spectra, the mechanism of allostery for the heterotropic effects between caffeine and acetaminophen or midazolam and alpha-naptho flavors with CYP3A4, and to initiate SAR-by-NMR to map ligand binding sites in uniformly deuterated, 15N-Phelabeled CYP3A4; 3) to monitor conformational dynamics of CYP3A4 via limited proteolysis/electrospray mass spectrometry as a function of ferric/ferrous redox state and ligand binding; 4) to map the CYP3A4/Cyt b5 binding surface via site-directed mutagenesis and catatylic turnover experiments, and determine whether specific interfacial residues contribute to Cyt b5-dependent allosteric effects. In addition, where possible, parallel experiments will be performed with CYPeryF, a soluble homolog for which X-ray crystallographic analysis is possible. In the long term, x-ray structures of
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Acetaminophen
[CYPeryF.ligand] complexes will be sought, via collaboration, in order to correlate allosteric effects with CYP structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF DRUG INTERACTIONS AND REACTIVE METABOLITES Principal Investigator & Institution: Nelson, Sidney D.; Dean of Pharmacy; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term objectives of the research described in this project are to understand mechanisms by which the widely used analgesic/antipyretic, acetaminophen, interacts with other drugs, and to characterize at the molecular level enzymes involved in the interactions. This is important to avoid life-threatening hepatic necrosis initiated by N-acetyl-p- benzoquinone imine, a reactive metabolite of acetaminophen formed by several cytochrome P450s that metabolize many other drugs. Results of previous studies implicate CYP2E1 and CYP2A6 as major catalysts in the oxidation of acetaminophen to its toxic quinoneimine and non-toxic catechol metabolites, respectively, and inhibition/induction of CYP2E1 by other drugs, such as isoniazid and ethanol, can increase or decrease risk of hepatotoxicity caused by acetaminophen depending on the time of ingestion relative to consequences of ligand regulation of CYP2E1. We propose to continue our studies of P450s responsible for the oxidation of acetaminophen in the next grant period. The first Specific Aim of this proposal is to construct active site models of CYP2E1 and CYP2A6 that are consistent with the different product selectivities of these two P450 isoforms for the quinoneimine and catechol metabolites of acetaminophen. A multi-tiered approach will be used that incorporate the results of NMR paramagnetic relaxation studies, homology and CoMFA modelling, mutagenesis experiments, and studies with mechanism- based inactivators. The second Specific Aim is to assess the roles of CYP2E1, CYP3A4 and dysregulation of hepatocyte mitochondrial glutathione status in the market toxicity of acetaminophen in individuals who chronically consume ethanol. This interaction has been suggested to be the leading cause of acute liver failure in the U.S. The interactions is multifaceted and the proposed studies continue an evaluation of this interaction initiated during the last grant period. A rat model will be used to investigate the separate effects of changes in acetaminophen reactive metabolite formation clearance and hepatocyte mitochondrial GSH status on hepatocellular damage. A series of studies will be conducted in human volunteers to determine the contribution of CYP2E1 and CYP3A P450 isoforms to acetaminophen reactive metabolite formation in vivo at acetaminophen doses relevant to the interaction and the effects that moderate drinking of alcoholic beverages and starvation have on this clinical syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METABOLIC REGULATION BY THE NUCLEAR RECEPTOR CAR Principal Investigator & Institution: Moore, David D.; Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 14-MAR-2003; Project End 31-DEC-2006 Summary: (provided by applicant): In the natural environment, organisms are constantly exposed to a wide range of potentially toxic foreign compounds, or xenobiotics. Organisms also produce endogenous toxic compounds that must be metabolized. In mammals, these include bilirubin and bile acids. Because the identities
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and the concentrations of both exogenous and endogenous toxic agents can change quickly, their management is a complex problem that must be addressed in a flexible and dynamic manner. The nuclear hormone receptors CAR and PXR are central regulators of the response to xenobiotic challenges. In addition, PXR has recently been implicated in bile acid metabolism and preliminary results suggest that CAR is a central regulator of bilirubin clearance. Thus, this proposal is based on the hypothesis that CAR is a key regulator of specific metabolic responses to both exogenous and endogenous compounds. Its long-term goal is to understand these regulatory functions of CAR and their integration with those of PXR and other metabolic regulators. The specific aims are to: 1) use knockout mouse models to identify specific and overlapping target genes for CAR and PXR in liver and other tissues, and determine the consequences of the loss of both the CAR and PXR genes; 2) use knockout mice to define the role of CAR in the response to xenobiotic compounds with important effects on liver metabolism, including the over-the-counter analgesic acetaminophen and the plant-derived hepatoprotectant silybin; and 3) define the role of CAR in the regulation of endogenous metabolic pathways, particularly bilirubin clearance. The xenobiotic response resembles the immune response in interesting ways. For example, both produce specific and appropriate responses to an extremely diverse array of potential threats. Increased understanding of the complex regulation of immune responses has led to significant insights into pathological processes and also to new therapeutic avenues. We believe that a better understanding of the xenobiotic response may generate analogous benefits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MITOCHONDRIAL DEHYDROGENASES
SHORT
CHAIN
3-OH-ACYL-COA
Principal Investigator & Institution: Strauss, Arnold W.; Professor and Chair; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 20-AUG-1999; Project End 30-JUN-2004 Summary: Mitochondrial fatty acid beta-oxidation is the major source of energy in highly oxidative mammalian tissues and is essential for intermediary metabolism and production of ketone bodies in liver. Human genetic defects in fatty acid oxidation genes cause acute liver failure, a Reye's syndrome-like phenotype of hypoketotic, hypoglycemia; cardiomyopathy; skeletal myopathy; or sudden, unexpected childhood death. This pathway consists of four enzymatic steps catalyzed by 12 different nuclearly-encoded enzymes that are developmentally-regulated and tissue- specifically expressed. This proposal focuses on two enzymes catalyzing the third step, the short chain 3-hydroxy-acyl-CoA dehydrogenases (SCHAD). Aims 1 and 2 will examine the hypothesis that tissue-specific and developmental expression of the SCHAD-1 and -2 genes is coordinated with other fatty acid oxidation enzyme genes and involves nuclear hormone receptor transcription factors responsive to energy requirements and nutritional cues. Aim 2 will use the human SCHAD-1 gene and in vitro transfection and transgenic mice to locate critical regulatory sequences. Based upon the SCHAD-1 crystal structure and protein homologies, Aim 3 will determine structure-function relationships of SCHAD-1 of normal and mutant SCHADs after expression in bacteria to explore the hypothesis that SCHAD-1 and long chain 3-hydroxy- acyl-CoA dehydrogenase share common structural domains. Using the human gene sequences we have determined, Aim 4 will delineate SCHAD-1 or -2 mutations in children to examine the proposal that SCHAD deficiency and environmental stresses cause a Reye's syndrome-like phenotype of acute hepatic failure. Aim 5 will examine the effects of the three human SCHAD-1 mutations we have discovered on structure and function, the pathogenetics of SCHAD
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Acetaminophen
deficiency, to explore the hypothesis that SCHAD missense mutations result in rapid intramitochondrial degradation secondary to misfolding. Aim 6 is to define the phenotype of SCHAD-1 gene ablation we created in mice as a model of human disease, to examine the effects of environmental and drug (aspirin and acetaminophen) stressors on outcome and to similarly study an SCHAD-2 knockout. These studies will augment understanding of the pathogenesis of fatty acid oxidation disorders causing acute liver failure, cardiomyopathy, and sudden death in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR DETERMINANTS OF UGT FUNCTION Principal Investigator & Institution: Court, Michael H.; Assistant Professor; Pharmacol & Exper Therapeutics; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from Applicant's Abstract): Glucuronidation, catalyzed by the UDP-glucuronosyltransferase (UGT) enzymes, is an important metabolic pathway involved in the inactivation and excretion of a multitude of drugs, toxins, potential carcinogens and endobiotics. The long-term objectives of this research are to elucidate the molecular determinates of individual variability in UGT1A6 function. In doing so, it may then be possible to identify individuals within a population that may be at high risk for adverse drug reactions and interactions, susceptibility to environmental toxins and carcinogens, as well as those with inborn errors of endogenous metabolism. UGT1A6 preferentially glucuronidates planar phenolic xenobiotics and substantially contributes to the biotransformation of acetaminophen. Acetaminophen glucuronidation in humans appears to be heterogenous and the molecular basis for this phenomenon is currently unknown. There is evidence for functionally relevant polymorphisms in the human UGT1A6 gene, which may affect either substrate affinity or enzyme content. Furthermore, recent studies suggest that UGT isoforms can form heterodimers which could modulate UTG1A6-mediated glucuronidation through protein-protein interactions. Three specific aims are proposed: (1) To utilize acetaminophen as a probe substrate for UTG1A6-mediated glucuronidation which will be substantiated by comparative activity and enzyme kinetic determinations using currently available cDNA-expressed UGT isoforms, and by isoform-specific immunoinhibition of acetaminophen glucuronidation in human liver microsomes: (2) To investigate the influence of polymorphisms in the UGT1A6 gene on isoenzyme content and specific activity ascertained by comparisons of expressed wild-type and variant UGT1A6, and by phenotypic-genotypic analyses using human liver microsomes and (3) To investigate the potential role for protein-protein interactions in modulating UGT1A6-mediated glucuronidation by identifying interacting proteins with the yeast two-hybrid expression system, and substantiating the functional significance of these interactions by coexpression studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MRP PROLIFERATION
2
(CMOAT)
EXPRESSION
IN
HEPATOCELLULAR
Principal Investigator & Institution: Manautou, Jose E.; Professor; Pharmaceutical Sciences; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, Ct 06269 Timing: Fiscal Year 2000; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: It is known that hepatocytes undergoing active replication in response to mitogenic stimulation or during regeneration following chemical toxicity are resistant to
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the actions of hepatotoxic agents. However, the mechanism(s) for such resiliency remains unknown. Pilot studies from our laboratory demonstrate that hepatocytes induced to proliferate following the administration of sublethal doses of two model hepatotoxicants (acetaminophen and carbon tetrachloride) have elevated expression of the canalicular ATP-dependent efflux pump for organic anions known as MRP-2, alternatively known as canalicular MRP (cMRP) or c MOAT. We hypothesize that induction of hepatocellular proliferation results in an increased expression of this protein. The overall goal of the studies in this proposal is to better characterize the upregulation of this transport protein, which could contribute to the resiliency of proliferating hepatoyctes to chemically, induced injury. Our first goal is to examine the temporal alterations in MRP-2 expression and its tissue distribution during hepatocellular regeneration. Then we will determine if induction of hepatocellular replication in vivo using other models of compensatory hyperplasia and direct mitogenesis similarly enhance the expression of MRP-2. The studies outlined in this AREA grant should provide the foundation for future studies intended to elucidate the functional consequences of changes in the expression of this protein in proliferating hepatocytes. We would like to put forward the notion that up-regulation of MRP-2 may be one of several mechanisms by which proliferating hepatocytes acquire resistance to chemical injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL THERAPIES FOR ACETAMINOPHEN TOXICITY Principal Investigator & Institution: James, Laura P.; Pediatrics; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 30-NOV-2004 Summary: (adapted from the application) The long term goal of this award is to develop therapies, based on new mechanistic data, that can be utilized in the treatment of the acetaminophen (APAP) overdose patient. At therapeutic doses, APAP is metabolized to the reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by glutathione (GSH). With overdose, GSH is depleted and NAPQI covalently binds to proteins. The antidote, N-acetylcysteine (NAC) increases hepatic GSH and detoxifies NAPQI but its efficacy beyond 16 hrs is controversial. Hepatotoxicity is usually not evident until 48-72 hrs. The mechanism of the late phase of toxicity is unknown. Recent work has shown that activation of inflammatory mediators occurs with toxicity. It has been demonstrated in a murine model that nitrotyrosine adducts, acetaminophenprotein adducts, and toxicity co-localize in the same centrilobular cells. Nitrotyrosine occurs via peroxynitrite, a species formed from nitric oxide (NO) and superoxide. NO synthesis correlates with toxicity; iNOS knockout mice are less susceptible to toxicity; and Kupffer cell/macrophage inactivators decrease toxicity and tyrosine nitration. We postulate that the late phase in human toxicity (16-72 hrs) is a result of activation of Kupffer cells/macrophages, and possibly other cells, leading to the formation of peroxynitrite and inflammatory mediators. We hypothesize that treatments that decrease peroxynitrite formation can be effectively utilized to treat patients in the late phase of toxicity. This hypothesis will be tested through the following Specific Aims: 1.) Evaluate the involvement of pro- and anti-inflammatory cytokines in APAP hepatotoxicity and the effect of cytokine modulation on hepatotoxicity in the mouse. 2.) Evaluate the efficacy of continuous infusion NAC in the late phase of toxicity. (Oral NAC has a very low bioavailability). 3.) Examine the time course of nitrotyrosine adducts and inflammatory cytokines in the APAP overdose patient. The development of this applicant into an independent researcher will be accomplished through this
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Acetaminophen
proposal performed under the guidance of well-established mentors, in a university research environment, with training in various analytical methods to assess drug toxicity in animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ONTOGENY OF DRUG BIOACTIVATION AND IDIOSYNCRATIC ADRS Principal Investigator & Institution: Leeder, James S.; Chief; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Idiosyncratic adverse drug reactions (ADRs) are relatively rare, but potentially life-threatening events in which the determinants of susceptibility (largely unknown) are thought to be unique to the individual experiencing the adverse event. They can occur throughout the age spectrum but tend to be underemphasized in the pediatric literature yet children appear to be at increased risk for certain idiosyncratic ADRs such as valproate hepatotoxicity and cutaneous reactions to lamotrigine. An important step in the development of an idiosyncratic ADR appears to be biotransformation of the implicated drug to a chemically reactive metabolite ("bioactivation") that is capable of binding to cellular macromolecules and producing cell death directly or indirectly through initiation of an immune response. Although developmental changes in drug metabolizing enzymes such as the cytochromes P450 (CYPs) and glucuronosyl transferase (UGTs) have been characterized in children, little is known about the ontogeny of drug bioactivation as children grow and develop. Using biomarkers of acetaminophen (APAP), carbamazepine (CBZ) and valproic acid (VPA) bioactivation (and detoxification) in vivo, the goals of this research program are 1. to characterize the ontogeny of the drug bioactivation biomarkers in vivo and in vitro and 2. to identify the pharmacogenetic determinants of interindividual variability in APAP, CBZ and VPA biomarker expression during growth and development. To achieve these goals, two longitudinal "bioactivation" phenotyping studies will be conducted 1. in healthy children following a single test dose of APAP (15 mg/kg as Tylenol(r) alcoholfree solution, 80mg/0.8ml) and 2. in epileptic children routinely receiving CBZ or VPA for medical management of their disease involving NICHD PPRU sites in Kansas City, MO, Shreveport, LA, and Little Rock, AR. For each study, urine is collected overnight and analyzed for the presence of parent drug, "non-toxic" metabolites and conjugated l metabolites of candidate reactive metabolites. Specific urinary metabolite ratios will be used to determine the changes in reactive metabolic "burden" that occur during growth and development with specific reference to changes in CYP activities identified in longitudinal phenotyping studies currently underway. Paired DNA samples from the extremes of the population distributions will be subjected to a concerted search by DNA sequencing and fragment analysis for single nucleotide polymorphisms (SNPs) that contribute to inter-individual variability in drug bioactivation. It is anticipated that the results of this program will allow critical periods of increased bioactivation and thus, potential vulnerability to idiosyncratic ADRs, to be identified for subsequent prospective investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ONTOGENY OF PHASE II ENZYMES: SULT, UGT, GST Principal Investigator & Institution: Behm, Martin O.; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108
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Timing: Fiscal Year 2003; Project Start 23-MAY-2003 Summary: (provided by applicant): The goal of rational drug therapy is to produce a desired pharmacological response in an acceptable and predictable manner while minimizing undesired events. With respect to drug distribution (i.e. pharmacokinetics) and metabolism (i.e. biotransformation), children are not simply small adults. The biotransformation pathways in children are neither static over time, nor progress in a linear manner from fetal life through neonatal life and then into childhood, adolescence, and adulthood. In order to avoid therapeutic failure or unwanted toxicity, the rate of these biotransformations with respect to developmental state must be appreciated. While the ontogeny of Phase I pathways such as CYP2D6 and CYP3A4 over the first year of life has been studied, the only Phase II enzyme similarly studied is NAT2 which represents only a small proportion of Phase II biotransformations. APAP is one of the most commonly utilized pharmaceutics in pediatrics. Moreover, in a single therapeutic dose, undesired side effects are minimal. APAP is metabolized by three Phase II biotransformations {i.e. sulfotransferase (SULT), glutathione-S-transferase (GST), and glucuronosyltransferases (UGT)}, which represent three of the most important, both qualitative and quantitative, Phase II reactions. While neonatal studies indicate that, they have less absolute phase II activity and reduced UGT activity relative to SULT activity. To date, there is no in vivo data, which define the changes in activity of these important pathways during the first year of life. The longitudinal assessment of the metabolic ratio of APAP and its metabolites will provide this important information. The information gained from general proposal may also be applied to other important drugs metabolized by these pathways such as zidovudine, morphine, and lorazepam. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NECROSIS
OXIDANT
MECHANISMS
IN
DRUG-INDUCED
HEPATIC
Principal Investigator & Institution: Smith, Charles V.; Professor; Children's Research Institute 700 Children's Dr Columbus, Oh 43205 Timing: Fiscal Year 2003; Project Start 01-JUL-1998; Project End 31-MAR-2007 Summary: (provided by applicant): Chemically reactive intermediates cause the toxicities of a number of drugs and environmental chemicals and contribute to the pathogeneses of many human diseases through covalent modifications of biological molecules. Specific reactive oxygen and nitrogen species, radicals, free radicals, and other oxidant species exhibit different properties and reactivities, and efforts to prevent or treat the adverse effects of oxidant challenges require that we understand the properties of the reactive intermediates and the mechanisms by which they act. The principal goal of the research described in the present application is to elucidate these mechanisms. Previous studies implicated the loss of protein thiols in mechanisms of oxidant injury, but we have consistently not observed marked shifts in protein thiol status in toxicologically relevant models, particularly in vivo. In several models of oxidant cell killing, the data suggest that oxidations characteristic of those catalyzed by redox-active iron chelates correlate more closely with tissue damage than do thiol/disulfide redox shifts. Recent preliminary data indicate that reactive nitrogen species may contribute significantly to the mechanisms of injury in the primary models we study, and the relative contributions of these mechanisms need to be investigated. Specific Aim 1 is to test the hypothesis that specific products of oxidation of hepatic proteins other than disulfides will provide biomarkers of the molecular (chemist definition of molecular) mechanisms responsible for oxidant-mediated hepatic necrosis in vivo. Despite the absence of global depletion of protein thiols in relevant models of
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oxidant tissue damage, several lines of evidence indicate that effects on protein thiols are important determinants of lethal cell injury, and the studies described in Specific Aim 2 are designed to test the hypothesis that compartmentalized and molecularly selective thiol/disulfide shifts and related changes contribute significantly to oxidant injury. The major models we employ are based on toxicities of diquat, acetaminophen, and furosemide in vivo and in vitro, and a limited set of model oxidants for studies in vitro. Therapeutic uses of acetaminophen and furosemide are extensive, and diquat and paraquat are widely used herbicides. Although most recognized human toxicities arise from acute exposures or overdoses, often intentional, emerging evidence suggests that chronic, low dose exposures to these agents may cause more adverse effects than are appreciated at the present time. However, our major interest in the study of the effects of these toxicants is to understand the fundamental principles and concepts of druginduced cell death in vivo, with a primary focus on oxidant-induced hepatic necrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PAIN AND BEHAVIORAL SYMPTOMS IN DEMENTIA: A PILOT STUDY Principal Investigator & Institution: Miller, Lois L.; Population Base Nursing; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-JAN-2005 Summary: The purpose of this study is to test an intervention focused on the treatment of chronic pain for institutionalized older adults with dementia, with the intention of also reducing protective behavioral symptoms, such as aggression. A secondary purpose is to understand the mechanism that underlies the relationships among morning care, observed pain, and protective behavioral symptoms, both in the absence and presence of the proposed intervention. Older persons are at special risk for unidentified and under treated pain, often receiving significantly less analgesic medications than their cognitively intact peers. In addition, protective behavioral symptoms are exhibited by as many as 90 percent of persons with dementia. Although researchers and clinicians have hypothesized an association between pain and protective behavioral symptoms, little research has explored this relationship. This quasi-experimental study will use a 3-group repeated measures design with an untreated control group, to evaluate the effects of an individualized pain treatment intervention on nursing home residents with dementia. A purposive sample of 30 residents who are moderately to severely cognitively impaired, have at least one potentially painful chronic musculoskeletal condition, and exhibit protective behavioral symptoms (resistiveness to care, verbal and/or physical aggression) will be selected from 3 nursing homes (n=10 per facility). The Comfort And Responsiveness Enhancement (CARE) intervention, implemented by an advanced practice nurse consists of two components: 1) an analgesic drug component and 2) a psychosocial component. The two treatment components will be introduced in opposite sequence in intervention facilities, and during the final phase each participant will be exposed to the additive CARE intervention, which is expected to be associated with the best outcomes for participants. Outcomes of interest include self- report of pain, observed pain, protective behavioral symptoms, analgesic drug use, and psychosocial intervention use. Analysis of the effects of the intervention will use ANOVA if possible, or the corresponding nonparametric analytic technique (Wilcoxon signed rank sum tests). Content analysis of field notes kept throughout the intervention will be used to modify the intervention and evaluate the feasibility of testing it in a larger randomized clinical trial.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PAIN RELIEVING PROPERTIES OF ANALGESIC METABOLITES Principal Investigator & Institution: Vaccarino, Anthony L.; St. Charles Pharmaceuticals 2020 Gravier St New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 15-MAR-2004 Summary: (provided by applicant): Acetaminophen is used extensively in the management of mild to moderate pain. Even so, acetaminophen can cause hepatotoxicty after ingestion of large doses or from chronic use of smaller doses, particularly in the elderly, when liver function is compromised, or with concurrent alcohol use. Acetaminophen-induced liver injury is due not to the drug itself but to the formation of a toxic metabolite that normally would be detoxified by conjugation with glutathione. However, with an acute overdose or chronic use, glutathione stores are depleted and the toxic metabolite binds to liver cell proteins and causes hepatic necrosis. We have been exploring a series of new and proprietary acetaminophen derivatives, in which the lead compound (SCP-1) has good oral efficacy and produces little if any hepatotoxicity. Because the metabolic conversion of SCP-1 to acetaminophen is minimal, SCP-1 has its effects through different pathways than acetaminophen and SCP-1 is not a 'pro-drug' of acetaminophen. This Phase I application explores whether two major SCP-1 metabolites possess analgesic activity without hepatotoxicity in order to (1) understand the mechanisms of SCP-1 drug action, and (2) determine the feasibility of developing these metabolites for use in targeted populations in which the biotransformation of analgesic medications, including acetaminophen or SCP-1, could reduce therapeutic activity and/or increase the unwanted side-effects. It will determine whether the two SCP-1 metabolites have analgesic effects comparable to or better than SCP-1 or acetaminophen in two animal models of pain. It will also determine hepatotoxicity after chronic and acute dosing. If the SCP-1 metabolites show analgesic properties without hepatotoxicity, further drug development will be proposed under a Phase II SBIR with eventual clinical trials in special populations that have high levels of factors that influence the biotransformation of drugs into active metabolites, including patients with liver disease, malnutrition, obesity, genetically determined polymorphisms, concurrent use of drugs that inhibit metabolic enzymes, alcohol use, and the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEDIATRIC DRUG EVALUATION RESOURCE Principal Investigator & Institution: Wilson, John T.; Pediatrics; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2002; Project Start 01-JAN-1994; Project End 31-DEC-2003 Summary: Five recent significant events offer validation for resolving the dilemma about off-label drug use in children: 1) The FDA issued regulations for pediatric labeling of drugs in 1994, 2) Both the Drug Information Association and Pharmaceutical Research and Manufacturers of America held symposia to focus the attention of industry, i.e., about 80 percent of drugs are either not FDA approved for children or have extensive off-label use and inadequate dosing information, 3)The FDA Modernization and Accountability Act (PL 105-115) with its Pediatric component was enacted by Congress, 4) Five meetings of high international visibility addressed the issue, and 5) A Presidential directive to FDA caused a proposed rule on pediatric labeling. This dilemma can now be corrected by pediatric drug trials to meet FDA criteria for dose,
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Acetaminophen
efficacy and safety data. The NICHD PPRU Network Program provides resources for these trials. LSUMC-S PPRU contributes to 10 priority levels set by the 1993 RFA and by intercurrent National Steering Committee (NSC) meetings. Accomplishments for each priority are described in the Progress Report. Notable are pediatric therapeutic advances in a thermo-regulatory basis for antipyretic drug action, pentoxifylline for sickle cell disease, and clinical trial efficacy and safety data for a new formulation of acetaminophen submitted to FDA for labeling. LSUMC-S continued participation in this program sets two goals. 1. Provide a resource to acquire clinical data on new and marketed drugs, and 2. Investigate the pharmacology of new molecular entities for effective and safe use in children. To accomplish these goals, LSUMC-S offers: (1) A suitable clinical pharmacology program with willing investigators, a population of accessible patients, a children's clinical research facility, experienced principal investigator, evidence of industry collaboration, a core laboratory, data management resource, institutional commitments, and research nurse staff, (2) A description of two protocols which address major areas of pediatric therapeutics (sickle cell disease and adolescent smoking), (3) Continuation of active protocols for the Network, (4) Integration of a clinical and basic science team approach which applies pharmacokinetic/pharmacodynamic modeling techniques to our understanding of agerelated differences in drug disposition and efficacy, (5) Matrix Management based on Good Laboratory and Clinical Practice (GLP and GCP) guidelines which are implemented by standard operating procedures for efficient utilization of resources, and (6) A training environment for those responsible for the health of children. The LSUMCS PPRU research plan focuses on crucial pediatric pharmacotherapy issues to increase data for drug prescribing and FDA approval of labeling. 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
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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: PHARMACOGENETICS OF SULFATE CONJUGATION Principal Investigator & Institution: Blanchard, Rebecca L.; Associate Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002; Project Start 10-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Sulfate conjugation reactions are critical in the biotransformation of steroid hormones, neurotransmitters and several drugs. Sulfation reactions are catalyzed by cytosolic sulfotransferases (SULTs). SULT1 Al is a SULT isoform that catalyzes the conjugation of endogenous and exogenous estrogens as well drugs such as acetaminophen, minoxidil and 4-hydroxytamoxifen. SULTI El is a distinct SULT isoform that also sulfates estrogens. We have recently identified three common SULT1A1 alleles with different frequencies in Caucasian and African American populations. One of those alleles, SULTIA1 *2 was associated with significantly lower SULT1A1 activity in human tissues. The other allele, SULT1A1*3, is frequent in the African American population (23 percent) but not in Caucasians (1 percent). Biochemical analysis of the recombinant SULT1A1 *3 allozyme indicated that it had a ten-fold greater affinity for the sulfation cosubstrate, but the functional significance of this allele in human tissue has not yet been evaluated. This proposal seeks to examine the functional and clinical significance of those SULT1A1 polymorphisms, particularly in the context of SULT1 El redundancy. Purified recombinant SULT1 Al allozymes will be biochemically characterized with estrogen and antiestrogen substrates and compared with the biochemistry of another SULT isoform, SULT1 El. The association between the SULT1A1 *3 allele and the level of SULT1A1 activity and immunoreactive protein will be examined in platelets from African American individuals to determine genotype/phenotype correlation. Preliminary data suggested that the SULT1 Al *2 protein and/or mRNA was less stable than the SULT1 Al *1 enzyme. Therefore, the kinetics of allele-dependent SULT1 Al protein and mRNA synthesis and degradation will be assessed. Proliferative and transcriptional response to 17beta-estradiol, 2methoxyestradiol and 4-hydroxytamoxifen will be studied and compared in MCF-7 cells stably expressing SULT1 El or SULT1A1 allozymes. Finally, the association between SULT1A1 alleles and specific breast cancer characteristics will be examined in a cohort of 600 Caucasian and African American women with breast cancer. These results will increase our understanding of the contribution of SULT1A1 pharmacogenetics to individual variation in response to estrogens and an important antiestrogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREDICTIVE POLYMORPHISMS
P450
TOXICOLOGY:
METABOLISM
AND
Principal Investigator & Institution: Harris, Danni L.; Computational Chemist; Moltech Corporation 2495 Old Middlefield Way Mountain View, Ca 94043
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Timing: Fiscal Year 2004; Project Start 11-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Toxic and carcinogenic side effects of drug administration are often due to their cytochrome P450 (CYP450) metabolism. It has been estimated that 1-in 15 hospital admissions is due to adverse drug effects. In addition, prescribed drugs account for 106,000 deaths and 2.2 million adverse reactions. Both interindividual and population subgroup variations in metabolism of drugs and xenobiotics have profound clinical consequences. The ability to predict metabolism at the earliest stage of drug discovery would accelerate the pace by which efficacious agents lacking toxicity are developed. This approach also takes advantage of the growing pharmacogenetics knowledge pertaining to both genotypic and phenotypic effects on drug metabolism. Rapid progress in our understanding of the underlying principles of CYP450 metabolism has resulted from the convergence of structural and molecular biology with theoretical methods, capable of predicting the geometric and thermodynamic determinants of competitive metabolism. This has enabled us to predict the principal products of CYP450 metabolism of drugs by a combination of ligand-P450 configurational sampling, based on rapid flexible docking, and electronic determinants of metabolism by the active heme species of P450s. Critical appraisals of this approach indicate a robust ability to predict major metabolites of test drugs, including toxic products, such as N-acetyl-p-benzoquinoneimine derived from CYP2E1 acetaminophen metabolism. This initial appraisal will be extended to test predictions of an assembled large 3D structural drug database with associated metabolic and kinetic data. The overall goal of this Phase I SBIR is twofold: 1) to critically assess a method capable of making metabolism predictions of drugs, by the major mammalian CYP450 isoforms, on the timescale of minutes per lead compound using a desktop computer, and 2) the extension of this method to predict the effects of single nucleotide polymorphisms (SNPs) on metabolism. This dual approach will establish an in silico predictive toxicology product developed with corporate partnership in a phase II application, that will be invaluable, even at the earliest stages of molecular conception, to the drug discovery process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRENATAL NSAID USE AND MISCARRIAGE Principal Investigator & Institution: Li, De-Kun K.; Investigator; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Recent reports have revealed an increased risk of spontaneous abortion associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy. To further examine this association, we propose to conduct a cohort study among the members of the Kaiser Permanente Medical Care Program (KPMCP). All KPMCP women who have a positive pregnancy test performed in one of the 13 KPMCP facilities and who speak either English or Spanish will be screened for their NSAID use during pregnancy to identify NSAID-exposed women. Using methods developed in an earlier study of electromagnetic field exposure and the risk of spontaneous abortion, we will recruit 1500 pregnant women: 500 NSAID-exposed women and 500 unexposed women; to control for confounding by indication, we will also recruit 500 women who have used acetaminophen, but neither NSAIDs nor aspirin because acetaminophen shares many similar indications with NSAIDs, but has a different pharmacological effect. Detailed information on prenatal NSAID use and other medications will be ascertained during an in-person interview as soon as the positive pregnancy is identified. Any subsequent NSAID use after the interview will be further
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ascertained at the end of pregnancy or at 20 weeks of gestation. Self-reported NSAID use will be confirmed by medication bottles, prescription records, and the KPMCP pharmacy databases that capture all prescription NSAIDs and nonprescription NSAID obtained at KPMCP pharmacies. Spontaneous abortion and other pregnancy outcomes will be ascertained through linkage to the KPMCP databases and review of medical records. Unidentified pregnancy outcomes will be ascertained through follow-up telephone interviews. Cox proportional hazard regression will be used to examine the risk of spontaneous abortion associated with periconceptional NSAID use. In addition, the risk associated with dose, timing, and duration of NSAID use as well as other characteristics of NSAID use including current/past use and cumulative dose will be examined. The proposed study will be the first population-based prospective cohort study specifically designed to examine the risk of spontaneous abortion associated with prenatal NSAID use. The findings from this study will provide valuable information on the safety of periconceptional NSAID use that has significant public health implications because of the widespread use of NSAIDs in the general population and among women of reproductive age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QTL MAPPING OF MULTIPLE ANALGESIC MODALITIES Principal Investigator & Institution: Mogil, Jeffrey S.; Assistant Professor; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 22-SEP-2001; Project End 30-JUN-2006 Summary: (Adapted from the Investigator's Abstract) Pain sensitivity and response to pain inhibiting strategies exhibit large individual differences. The genetic portion of such variability can be studied using inbred mouse strains. The underlying genes can be localized and eventually identified using QTL mapping. In an attempt to explain the genetic factors underlying such variability, we propose to perform QTL mapping of four different analgesics: acetaminophen, epbatidine, U50-488, and WIN-55,212-2. Although these analgesics interact with distinct proteins, there exists a moderate to strong correlation among inbred strain responses to them, suggesting that "master" analgesia genes may be identified affecting all types of analgesia. Once QTLs are detected, we will attempt to learn their identity by a combination of candidate gene and positional cloning strategies. Clinical utility of this work may include the development of DNA tests predicting sensitivity to analgesics, novel therapies, and possibly gene therapy for chronic pain states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REACTIVE METABOLITES AND DRUG TOXICITY Principal Investigator & Institution: Hanzlik, Robert P.; Professor; Medicinal Chemistry; University of Kansas Lawrence Youngberg Hall Lawrence, Ks 660457563 Timing: Fiscal Year 2002; Project Start 01-AUG-1978; Project End 31-MAR-2004 Summary: Many simple organic molecules containing phenyl substituents or benzene rings become cytotoxic upon biotransformation to reactive electrophilic metabolites. Prime examples include halothane, acetaminophen and bromobenzene (BB). Their hepatotoxicity is correlated with covalent binding of reactive metabolites to cellular proteins. As a start toward elucidating the biochemical mechanism(s) of their cytotoxicity we identified the structures of ten adducts of BB metabolites to protein-SH groups; most arose via quinone metabolites, but we also found that BB-3,4-oxide (BBO), thought to be the primary "toxic" metabolite of BB, alkylates histidine and lysine as well
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as cysteine residues of rat liver proteins. Key questions concerning the mechanism of cell injury by reactive metabolites include the identity of the proteins they target and the functional consequences of their covalent modification. We recently identified several rat liver proteins targeted by BB metabolites. One was a nonspecific esterase also known to be a target for metabolites of halothane and molinate. Another, surprisingly, was epoxide hydrolase, which is supposed to detoxify BBO. To address the mechanism of BB-induced cytotoxicity it is essential to expand this list by identifying other liver proteins targeted by BB metabolites. In doing so we will emphasize mitochondrial proteins but will continue to explore cytosolic and microsomal proteins. To facilitate recognition of BBO adducts, we raised antibodies to p-bromophenyl-cysteine and demonstrated their utility for western blotting; we will now develop antibodies to pbromophenyl-histidine and p-bromophenyl-lysine as well. These antibodies, coupled with [C14]-BB, will give us a broad and powerful means for finding and identifying those proteins of greatest toxicological interest. Very little is known about the chemistry and consequences of protein adduction by reactive metabolites. Thus we will elucidate in detail the specific site(s), metabolite(s) and linkage(s) involved in adduct formation for select BB target proteins. For those target proteins which are enzymes, we will evaluate the effect of adduction on catalytic activity to assess its potential contribution to cell injury. Comparing the proteins modified by bromobenzene to those modified by other small bioactivated toxins may reveal the existence, or the lack of, a "common pathway" for chemically-induced cytotoxic responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF XENOBIOTIC-METABOLIZING CYP3A Principal Investigator & Institution: Zangar, Richard C.; Senior Research Scientist; Battelle Pacific Northwest Laboratories Box 999, 902 Battelle Blvd Richland, Wa 99352 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract) Cytochrome P450 3A (CYP3A) levels are important determinants of aflatoxin and acetaminophen toxicity and the uptake and elimination of numerous therapeutic agents. CYP3A protein has been reported to be stabilized by some CYP3A substrates. The PI reported that several structurally and functionally distinct agents that are not known CYP3A substrates alter CYP3A protein stability in primary cultured rat hepatocytes. The changes in CYP3A stability are consistent with effects of these agents on phospholipase C or D (PLC or PLD, respectively). Studies in microsomes have indicated that the PLD metabolite, phosphatidic acid (PA), is important in determining CYP3A stability. We propose to test this hypothesis that CYP3A protein stability is dependent upon microsomal PA levels and to further elucidate the molecular mechanism by which phospholipases and other enzymes that regulate PA levels contribute to CYP3A protein stability. The specific aims are: 1) To further establish the role of PLD and PLC in the regulation of CYP3A protein stability. 2) To determine if agents that alter CYP3A stability in primary cultured hepatocytes also function in in vitro incubations. 3.) To determine if PA analogs with different fatty acid moieties have distinct effects on CYP3A protein stability in microsomal samples. 4) To determine whether agents that regulate rat CYP3A stability act in a like manner in human primary cultured hepatocytes and microsomes. These studies will provide information that can be used to predict drug interactions by providing an understanding of the underlying molecular mechanisms involved in the post-translational regulation of CYP3A, and will test a new hypothesis regarding the interactions of phospholipase activities and a key drug-metabolizing enzyme. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REPRODUCTIVE HORMONES AND ACETAMINOPHEN STUDY Principal Investigator & Institution: Cramer, Daniel W.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: To compare gonadotropin, estradiol, and inhibin levels in women randomly assigned to take either 1 gm of acetaminophen or placebo daily over one menstrual cycle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESEARCH CENTER FOR PHARMACOLOGY AND DRUG TOXICOLOGY Principal Investigator & Institution: Morrow, Jason D.; Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-1977; Project End 30-JUN-2006 Summary: (provided by applicant) Research Center for Pharmacology and Drug Toxicology: Novel Mechanisms and Pharmacological Consequences of Arachidonate Oxygenation brings together a tightly-knit group of experienced investigators with a shared interest in arachidonic acid oxygenation to undertake research focused on the pharmacology, biochemistry, and biology of eicosanoids. The goal of this research is to identify new targets for the development of therapies to modulate the formation of eicosanoids in humans. Epidemiological and clinical studies suggest that oxygenated arachidonic acid species (eicosanoids) play an important role in human physiology and in diseases such as atherosclerosis, cancer and neurodegenerative diseases, among others. Thus, pharmacological manipulation of the formation of oxidized arachidonate species provides the opportunity to prevent or treat pathophysiological processes associated with these compounds. Nonetheless, a thorough understanding, at the molecular level, of factors influencing eicosanoid formation and action remains elusive. This Center comprises six research projects and two cores that will provide important insights into the role of oxygenated arachidonate species, derived either enzymatically or non-enzymatically, in human physiology and pathophysiology. A particular strength of our research program is that proposed projects integrate basic pharmacological, biochemical and molecular biological approaches with translational studies involving humans. The first Project tests the hypothesis that arachidonic acid esterified to glycerol is a novel and specific substrate for cyclooxygenase-2 and results in the formation of unique glyceryl prostaglandins (PGs). The second Project will determine the extent to which acetaminophen and salicylate exert their therapeutic efficacy by inhibiting eicosanoid production in humans. The third Project will test the hypothesis that PGE2 and PGD2 modulate the immune response to inflammation in vivo. These studies will employ mice with targeted deletions of genes encoding PG receptors. Cyclopentenone PGs such as PGJ2 have been postulated to play a role in inflammatory and proliferative responses in cells and tissues but the extent to which they are formed in vivo is unknown. The fourth Project will examine the formation and metabolism of these eicosanoids in humans. 4-hydroxynonenal is a bioactive lipid derived from the fragmentation of peroxidized arachidonic acid that is postulated to mediate adverse effects of oxidant stress. The fifth Project will focus on mechanisms by which this compound is formed in vivo and its biological effects. The sixth Project will test the hypothesis that the oxidation of cholesteryl arachidonate can be precisely defined in humans and leads to the formation of heretofore undescribed, biologically active, products containing complex cyclic structures. The investigators included in this
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research proposal are highly integrated both scientifically and intellectually and are extremely experienced in a number of facets of eicosanoid research. It is anticipated that the projects proposed will significantly advance our understanding of eicosanoid pharmacology and biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCF IN LIVER REPAIR AFTER HEPATECTOMY OR TOXIC INJURY Principal Investigator & Institution: Colletti, Lisa M.; Associate Professor; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant)The failing liver is the only vital organ for which we have no means of pharmacologic or mechanical support. The liver is also unique in that it can regenerate a normal functional cellular mass in response to many injuries, as opposed to most organs which repair themselves with non-functional scar. Liver failure is an important clinical problem that occurs after a variety of toxic, traumatic, and infectious insults. Liver failure also occasionally follows major hepatic resections for tumor. More importantly, hepatic resection is often precluded when a curative resection will leave an inadequate amount of functioning hepatic tissue, ultimately resulting in the death of the patient. Accidental and purposeful acetaminophen overdose accounts for 20 percent of acute liver failure cases in the U.S. Acetaminophen poisoning causes direct hepatocyte damage and patient survival relies heavily upon the liver's ability to recover from the damage and regenerate. Acetaminophen-induced liver injury is well characterized, however, the mechanisms of liver protection, repair, and regeneration have not been fully examined. This proposal examines a specific cytokine, stem cell factor (SCF), in hepatocyte protection and regeneration during acetaminophen-induced liver toxicity, as well as following 70 percent hepatectomy. SCF is well-known as an important leukocyte hematopoietic factor, involved in the proliferation and maturation of multiple leukocyte subsets, especially mast cells. More recently, it has been shown to be an important factor in the development of normal structural cells, such as hepatocytes. We will utilize two murine models, acetaminophen poisoning and 70 percent hepatectomy, to investigate SCF's effects following liver injury. We hypothesize that SCF functions via two mechanisms, having anti-apoptotic protective effects, as well as enhancing the hepatocyte regenerative response. To test this postulate, we will focus on mechanisms of SCF-associated liver repair utilizing the following specific aims: 1) To examine the expression, production, and cellular source of hepatic SCF following 70 percent hepatectomy or acetaminophen-induced injury, 2) To examine the regulation of transmembrane versus soluble SCF and its receptor, c-kit, in the setting of toxic or traumatic hepatic injury, 3) To investigate SCF's effects and mechanism(s) of action on hepatocyte apoptosis and proliferation after toxic or traumatic hepatic injury, and 4) To investigate the interactions of SCF and IL-6 in the liver's recovery from toxic or traumatic injury. These studies will help to elucidate novel mechanisms in SCFmediated hepatocyte protection and regeneration in a clinically relevant liver resection and toxicity model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUPPRESSION OF CYP2E1 IN DRUG INDUCED LIVER INJURY Principal Investigator & Institution: Linder, Mark W.; Pathology and Lab Medicine; University of Louisville University of Louisville Louisville, Ky 40292
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Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term career goals are to develop the clinical discipline of pharmacogenomies and the short-term goal is to develop an independent patient-oriented research career focusing on the validation and development of pharmacogenentic diagnostics. Environment: The University of Louisville has adopted pharmacogenetics as one of seven key areas for development. The Pharmacogenetic Diagnostics Laboratory (founded by Dr's Valdes and Linder) is one of the first CLIA certified clinical pharmaeogenetic laboratories in the world. Dr C. McClain (Co-mentor) is Director of the newly established Clinical Research Center at the University of Louisville Hospital. Preliminary findings: Within the proximal promoter of the CYP2E1 gene is a nucleotide sequence (cytokine response element) responsible for gamma-interferon (gamma-IFN)-dependent suppression of gene transcription. A naturally occurring polymorphisrn, G(-71)T within this sequence renders the CYP2E1 promoter insensitive to suppression by gamma-IFN. Hypothesis: Intracellular production of reactive-metabolic intermediates is regulated by a negative feedback mechanism sensitive to the structure of the CYP2E1 promoter. Polymorphism within the promoter sequence interrupts this feedback and leads to increased toxicity from reactive intermediate products. Approach: To test this hypothesis, we will; i) Investigate the mechanism of IFN-gamma mediated CYP2E1 suppression in humans, ii) Evaluate the influence of IFN-gamma on the LD 50 of CYP2E 1 substrates which undergo metabolic bioactivation, iii) Characterize the molecular detail of IFN-gamma dependent suppression of CYP2E1, and iv) Evaluate the relationship between the CYP2E1*7B allele and selected human diseases influenced by the catalytic properties ofCYP2E1. Significance: This research will identify a novel mechanism to explain variability in susceptibility to human disease resulting from exposure to medicinal and environmental substrates of CYP2E1. These findings may lead to development of a diagnostic test for identifying susceptible individuals and provide insight into potential therapeutic or preventive approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOLERABILITY & EFFECTIVENESS OF ROFECOXIB VS NAPROXEN Principal Investigator & Institution: Ballou, Stanley; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: This is a study to evaluate the tolerability and effectiveness of Rofecoxib 25 mg. q.d. vs. Naproxen 500 mg. B.I.D. after 12 weeks of treatment in patient with osteoarthritis of the knee, hip, hand, or spine. Osteoarthritis will be diagnosed with standardized clinical criteria. Patients who regularly use non steroidal antiinflammatory or acetaminophen for the treatment of osteoarthritis of the study joint will be studied. The primary aim is to test the gastrointestinal tolerability of the investigational drug. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “acetaminophen” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for acetaminophen in the PubMed Central database: •
Acetaminophen toxicity: suicidal vs accidental. by Gyamlani GG, Parikh CR.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111182
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An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen. by Chan K, Han XD, Kan YW.; 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31882
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Brief safety updates: acetaminophen, ASA and kava. by Wooltorton E.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134182
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COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. by Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129799
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Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H2 synthases. by Boutaud O, Aronoff DM, Richardson JH, Marnett LJ, Oates JA.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124540
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Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]. by Dippel DW, van Breda EJ, van der Worp HB, van Gemert HM, Meijer RJ, Kappelle LJ, Koudstaal PJ.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152640
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Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial. by Peter EA, Janssen PA, Grange CS, Douglas MJ.; 2001 Oct 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81582
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Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione Stransferase Pi. by Henderson CJ, Wolf CR, Kitteringham N, Powell H, Otto D, Park BK.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18834
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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Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroid antiinflammatory drugs. by Simmons DL, Botting RM, Robertson PM, Madsen ML, Vane JR.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15932
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Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites. by Senter PD, Al-Abed Y, Metz CN, Benigni F, Mitchell RA, Chesney J, Han J, Gartner CG, Nelson SD, Todaro GJ, Bucala R.; 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117529
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PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]. by Breda EJ, van der Worp B, Gemert MV, Meijer R, Kappelle J, Koudstaal PJ, Dippel DW.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101394
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Safe use of acetaminophen. by Barton KN.; 2003 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155941
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The risk of upper gastrointestinal complications associated with nonsteroidal antiinflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. by Garcia Rodriguez LA, Hernandez-Diaz S.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128885
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 acetaminophen, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “acetaminophen” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for acetaminophen (hyperlinks lead to article summaries): •
A 20-hour treatment for acute acetaminophen overdose. Author(s): Yip L, Dart RC. Source: The New England Journal of Medicine. 2003 June 12; 348(24): 2471-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802041&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A case-control study of acetaminophen use in relation to the risk of first myocardial infarction in men. Author(s): Rosenberg L, Rao RS, Palmer JR. Source: Pharmacoepidemiology and Drug Safety. 2003 September; 12(6): 459-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513659&dopt=Abstract
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A comparison of ketorolac tromethamine and acetaminophen codeine in the management of acute apical periodontitis. Author(s): Sadeghein A, Shahidi N, Dehpour AR. Source: Journal of Endodontics. 1999 April; 25(4): 257-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10425951&dopt=Abstract
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Acarbose and acetaminophen- a dangerous combination? Author(s): Sato A. Source: Hepatology (Baltimore, Md.). 1999 June; 29(6): 1914. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10383254&dopt=Abstract
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Acetaminophen (paracetamol) levels in human tears. Author(s): Lifshitz M, Weinstein O, Gavrilov V, Rosenthal G, Lifshitz T. Source: Therapeutic Drug Monitoring. 1999 October; 21(5): 544-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519453&dopt=Abstract
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Acetaminophen (paracetamol)-induced anaphylactic shock. Author(s): Bachmeyer C, Vermeulen C, Habki R, Blay F, Leynadier F. Source: Southern Medical Journal. 2002 July; 95(7): 759-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144085&dopt=Abstract
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Acetaminophen and hypertension: a causal association or pain mediated? Author(s): Brotman DJ. Source: Archives of Internal Medicine. 2003 May 12; 163(9): 1113-4; Author Reply 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742815&dopt=Abstract
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Acetaminophen and upper gastrointestinal complications. Author(s): Werner MU, Nielsen PR, Romsing J, Garcia Rodriguez LA, Hernandez-Diaz S. Source: Epidemiology (Cambridge, Mass.). 2002 September; 13(5): 605-6; Author Reply 606. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192234&dopt=Abstract
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Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis. Author(s): Anderson BJ, van Lingen RA, Hansen TG, Lin YC, Holford NH. Source: Anesthesiology. 2002 June; 96(6): 1336-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170045&dopt=Abstract
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Acetaminophen down-regulates interleukin-1beta-induced nuclear factor-kappaB nuclear translocation in a human astrocytic cell line. Author(s): Mancini F, Landolfi C, Muzio M, Aquilini L, Soldo L, Coletta I, Guglielmotti A, Mantovani A, Pinza M, Milanese C. Source: Neuroscience Letters. 2003 December 19; 353(2): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14664905&dopt=Abstract
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Acetaminophen exhibits weak antiestrogenic activity in human endometrial adenocarcinoma (Ishikawa) cells. Author(s): Dowdy J, Brower S, Miller MR. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2003 March; 72(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604834&dopt=Abstract
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Acetaminophen for osteoarthritis. Author(s): Towheed TE, Judd MJ, Hochberg MC, Wells G. Source: Cochrane Database Syst Rev. 2003; (2): Cd004257. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804508&dopt=Abstract
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Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: a randomized, double-blind, placebo-controlled trial. Author(s): Pernerstorfer T, Schmid R, Bieglmayer C, Eichler HG, Kapiotis S, Jilma B. Source: Clinical Pharmacology and Therapeutics. 1999 July; 66(1): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430109&dopt=Abstract
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Acetaminophen hepatotoxicity without intentional overdose. Author(s): Mege J. Source: Pa Med. 1999 June; 102(6): 14-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399461&dopt=Abstract
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Acetaminophen hepatotoxicity. Author(s): Bromer MQ, Black M. Source: Clinics in Liver Disease. 2003 May; 7(2): 351-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879988&dopt=Abstract
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Acetaminophen hepatotoxicity: the first 35 years. Author(s): Rumack BH. Source: Journal of Toxicology. Clinical Toxicology. 2002; 40(1): 3-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990202&dopt=Abstract
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Acetaminophen hypersensitivity. Author(s): Kivity S, Pawlik I, Katz Y. Source: Allergy. 1999 February; 54(2): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221446&dopt=Abstract
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Acetaminophen in cerebrospinal fluid in children. Author(s): van der Marel CD, Anderson BJ, Pluim MA, de Jong TH, Gonzalez A, Tibboel D. Source: European Journal of Clinical Pharmacology. 2003 August; 59(4): 297-302. Epub 2003 July 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845506&dopt=Abstract
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Acetaminophen induces a caspase-dependent and Bcl-XL sensitive apoptosis in human hepatoma cells and lymphocytes. Author(s): Boulares AH, Zoltoski AJ, Stoica BA, Cuvillier O, Smulson ME. Source: Pharmacology & Toxicology. 2002 January; 90(1): 38-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005112&dopt=Abstract
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Acetaminophen intoxication and length of treatment: how long is long enough? Author(s): Kociancic T, Reed MD. Source: Pharmacotherapy. 2003 August; 23(8): 1052-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921251&dopt=Abstract
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Acetaminophen levels 4 and 7 hours after 2000 and 3000 mg single doses in healthy adults. Author(s): Sumida SM, Sato RL, Wong JJ, Yamamoto LG. Source: Hawaii Med J. 2003 January; 62(1): 6-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592742&dopt=Abstract
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Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro. Author(s): Bilir A, Altinoz MA, Attar E, Erkan M, Aydiner A. Source: Neoplasma. 2002; 49(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044058&dopt=Abstract
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Acetaminophen not associated with gastrointestinal toxicity: comment on the article by Rahme et al. Author(s): Cryer BL. Source: Arthritis and Rheumatism. 2003 July; 48(7): 2074-5; Author Reply 2075-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847704&dopt=Abstract
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Acetaminophen overdose? A quick answer. Author(s): Rumack BH. Source: The Journal of Pediatrics. 1999 September; 135(3): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10484784&dopt=Abstract
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Acetaminophen overuse in the Ohio Medicaid population. Author(s): Heaton PC, Cluxton RJ Jr, Moomaw CJ. Source: J Am Pharm Assoc (Wash Dc). 2003 November-December; 43(6): 680-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14717264&dopt=Abstract
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Acetaminophen poisoning in children: treat early and long enough. Author(s): Kearns GL. Source: The Journal of Pediatrics. 2002 May; 140(5): 495-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032510&dopt=Abstract
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Acetaminophen poisoning: an update for the intensivist. Author(s): Dargan PI, Jones AL. Source: Critical Care (London, England). 2002 April; 6(2): 108-10. Epub 2002 March 14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983032&dopt=Abstract
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Acetaminophen recommendation. Author(s): Mortensen ME, Cullen JL. Source: Pediatrics. 2002 September; 110(3): 646. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205273&dopt=Abstract
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Acetaminophen toxicity in children. Author(s): Mortensen ME. Source: American Family Physician. 2002 September 1; 66(5): 734. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322766&dopt=Abstract
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Acetaminophen toxicity. Opposite effects of two forms of glutathione peroxidase. Author(s): Mirochnitchenko O, Weisbrot-Lefkowitz M, Reuhl K, Chen L, Yang C, Inouye M. Source: The Journal of Biological Chemistry. 1999 April 9; 274(15): 10349-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10187823&dopt=Abstract
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Acetaminophen toxicity: suicidal vs. accidental. Author(s): Gyamlani GG, Parikh CR. Source: Critical Care (London, England). 2002 April; 6(2): 155-9. Epub 2002 February 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983042&dopt=Abstract
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Acetaminophen, aspirin, and renal failure. Author(s): Thurlow W. Source: The New England Journal of Medicine. 2002 May 16; 346(20): 1588-9; Author Reply 1588-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017163&dopt=Abstract
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Acetaminophen, aspirin, and renal failure. Author(s): Campo A. Source: The New England Journal of Medicine. 2002 May 16; 346(20): 1588-9; Author Reply 1588-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12015402&dopt=Abstract
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Acetaminophen-induced linear IgA bullous dermatosis. Author(s): Avci O, Okmen M, Cetiner S. Source: Journal of the American Academy of Dermatology. 2003 February; 48(2): 299301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582411&dopt=Abstract
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Acetaminophen-induced rhabdomyolysis. Author(s): Moneret-Vautrin DA, Morisset M, Humbert JC, Beaudouin E, Tupin N, Plantier L. Source: Allergy. 1999 October; 54(10): 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10536893&dopt=Abstract
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Acetaminophen's hidden dangers. Author(s): Karch AM, Karch FE. Source: The American Journal of Nursing. 2003 February; 103(2): 101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582346&dopt=Abstract
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Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. Author(s): Buckley NA, Whyte IM, O'Connell DL, Dawson AH. Source: Journal of Toxicology. Clinical Toxicology. 1999; 37(6): 753-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584587&dopt=Abstract
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Acute acetaminophen poisoning in children: kids aren't just little adults. Author(s): Bryant S, Bellamy L, Paloucek F, Wahl M. Source: The Journal of Emergency Medicine. 2003 May; 24(4): 472-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745056&dopt=Abstract
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Acute effects of acetaminophen on renal function and urinary excretion of some proteins and enzymes in patients with kidney disease. Author(s): Mitic-Zlatkovic M, Stefanovic V. Source: Renal Failure. 1999 September; 21(5): 525-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516997&dopt=Abstract
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Acute fatty liver of pregnancy and acetaminophen toxicity leading to liver failure and postpartum liver transplantation. A case report. Author(s): Gill EJ, Contos MJ, Peng TC. Source: J Reprod Med. 2002 July; 47(7): 584-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170538&dopt=Abstract
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Administering acetaminophen safely. Author(s): Acello B. Source: Nursing. 2003 November; 33(11): 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650379&dopt=Abstract
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Advancing NMR sensitivity for LC-NMR-MS using a cryoflow probe: application to the analysis of acetaminophen metabolites in urine. Author(s): Spraul M, Freund AS, Nast RE, Withers RS, Maas WE, Corcoran O. Source: Analytical Chemistry. 2003 March 15; 75(6): 1536-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659219&dopt=Abstract
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Alcohol and acetaminophen hepatotoxicity. Author(s): Dart RC, Kuffner E. Source: Archives of Internal Medicine. 2003 January 27; 163(2): 244-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546623&dopt=Abstract
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Alcohol, acetaminophen, and toxic effects on the liver. Author(s): Oviedo J, Wolfe MM. Source: Archives of Internal Medicine. 2002 May 27; 162(10): 1194-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020195&dopt=Abstract
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Alternating acetaminophen and ibuprofen in the febrile child: examination of the evidence regarding efficacy and safety. Author(s): Carson SM. Source: Pediatric Nursing. 2003 September-October; 29(5): 379-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14651311&dopt=Abstract
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Ameliorative effect of an urinary preparation on acetaminophen and D-galactosamine induced hepatotoxicity in rats. Author(s): Lai TY, Wu YW, Lin WC. Source: The American Journal of Chinese Medicine. 1999; 27(1): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10354819&dopt=Abstract
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An unusual case of acetaminophen overdose. Author(s): Tsang WO, Nadroo AM. Source: Pediatric Emergency Care. 1999 October; 15(5): 344-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10532667&dopt=Abstract
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Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in combination for paediatric day-case adenoidectomy. Author(s): Viitanen H, Tuominen N, Vaaraniemi H, Nikanne E, Annila P. Source: British Journal of Anaesthesia. 2003 September; 91(3): 363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925475&dopt=Abstract
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Brief safety updates: acetaminophen, ASA and kava. Author(s): Wooltorton E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 October 29; 167(9): 1034. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403745&dopt=Abstract
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By the way, doctor. I recently read that Tylenol and anti-inflammatory drugs can cause high blood pressure. This doesn't leave me with many pain relief options. What do you suggest? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2003 February; 10(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604441&dopt=Abstract
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Causes of Alzheimer's disease: paracetamol (acetaminophen) today? Amphetamines tomorrow? Author(s): Jones GR. Source: Medical Hypotheses. 2001 January; 56(1): 121-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11133268&dopt=Abstract
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Cerebral edema with herniation during acetaminophen-induced fulminant hepatic failure. Author(s): Nyberg SL, Pfeifer EA. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 July; 6(4): 495-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10915174&dopt=Abstract
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Change in pain threshold by meperidine, naproxen sodium, and acetaminophen as determined by electric pulp testing. Author(s): Carnes PL, Cook B, Eleazer PD, Scheetz JP. Source: Anesthesia Progress. 1998 Fall; 45(4): 139-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483385&dopt=Abstract
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Characteristics and risk factors of acetaminophen-induced hepatitis in Taiwan. Author(s): Wang K, Huang YS, Deng JF, Yang CC, Ger J, Tsai WJ, Wu JC, Chao Y, Chang FY, Lee SD. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1999 June; 62(6): 369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389295&dopt=Abstract
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Chronic acetaminophen overdosing in children: risk assessment and management. Author(s): Sztajnkrycer MJ, Bond GR. Source: Current Opinion in Pediatrics. 2001 April; 13(2): 177-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11317062&dopt=Abstract
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Chronic acetaminophen toxicity: a case report and review of the literature. Author(s): Lane JE, Belson MG, Brown DK, Scheetz A. Source: The Journal of Emergency Medicine. 2002 October; 23(3): 253-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426016&dopt=Abstract
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Chronopharmacokinetics of acetaminophen in healthy human volunteers. Author(s): Kolawole JA, Chuhwak PD, Okeniyi SO. Source: Eur J Drug Metab Pharmacokinet. 2002 July-September; 27(3): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365202&dopt=Abstract
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Clinical use of a bioartificial liver in the treatment of acetaminophen-induced fulminant hepatic failure. Author(s): Detry O, Arkadopoulos N, Ting P, Kahaku E, Watanabe FD, Rozga J, Demetriou AA. Source: The American Surgeon. 1999 October; 65(10): 934-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515538&dopt=Abstract
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Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain. Author(s): Edwards JE, McQuay HJ, Moore RA. Source: Journal of Pain and Symptom Management. 2002 February; 23(2): 121-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844632&dopt=Abstract
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Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain. Author(s): Palangio M, Damask MJ, Morris E, Doyle RT Jr, Jiang JG, Landau CJ, de Padova A. Source: Clinical Therapeutics. 2000 July; 22(7): 879-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945514&dopt=Abstract
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Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain. Author(s): Palangio M, Morris E, Doyle RT Jr, Dornseif BE, Valente TJ. Source: Clinical Therapeutics. 2002 January; 24(1): 87-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833838&dopt=Abstract
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Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain. Author(s): Palangio M, Wideman GL, Keffer M, Landau CJ, Morris E, Doyle RT Jr, Jiang JG, Damask M, de Padova A. Source: Clinical Therapeutics. 2000 May; 22(5): 600-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10868557&dopt=Abstract
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Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study. Author(s): Breivik EK, Barkvoll P, Skovlund E. Source: Clinical Pharmacology and Therapeutics. 1999 December; 66(6): 625-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613619&dopt=Abstract
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Comment: hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors. Author(s): Mortensen ME, Cullen JL. Source: The Annals of Pharmacotherapy. 2002 September; 36(9): 1481-2; Author Reply 1482-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196075&dopt=Abstract
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Comparative analgesia, cardiovascular and renal effects of celecoxib, rofecoxib and acetaminophen (paracetamol). Author(s): Graham GG, Graham RI, Day RO. Source: Current Pharmaceutical Design. 2002; 8(12): 1063-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11945151&dopt=Abstract
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Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine. Author(s): Freitag FG, Cady R, DiSerio F, Elkind A, Gallagher RM, Goldstein J, Klapper JA, Rapoport AM, Sadowsky C, Saper JR, Smith TR. Source: Headache. 2001 April; 41(4): 391-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318886&dopt=Abstract
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Comparison of oral versus normal and high-dose rectal acetaminophen in the treatment of febrile children. Author(s): Scolnik D, Kozer E, Jacobson S, Diamond S, Young NL. Source: Pediatrics. 2002 September; 110(3): 553-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205259&dopt=Abstract
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Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies. Author(s): Milsom I, Minic M, Dawood MY, Akin MD, Spann J, Niland NF, Squire RA. Source: Clinical Therapeutics. 2002 September; 24(9): 1384-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380631&dopt=Abstract
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Concerns about gastrointestinal safety of acetaminophen: comment on the article by Rahme et al. Author(s): Bannwarth B. Source: Arthritis and Rheumatism. 2003 July; 48(7): 2075; Author Reply 2075-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847706&dopt=Abstract
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Continuous low-level heat wrap therapy provides more efficacy than Ibuprofen and acetaminophen for acute low back pain. Author(s): Nadler SF, Steiner DJ, Erasala GN, Hengehold DA, Hinkle RT, Beth Goodale M, Abeln SB, Weingand KW. Source: Spine. 2002 May 15; 27(10): 1012-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004166&dopt=Abstract
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Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Author(s): Manyike PT, Kharasch ED, Kalhorn TF, Slattery JT. Source: Clinical Pharmacology and Therapeutics. 2000 March; 67(3): 275-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741631&dopt=Abstract
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Correlation of in vitro and in vivo acetaminophen availability from albumin microaggregates oral modified release formulations. Author(s): Torrado G, Carrascosa C, Torrado-Santiago S. Source: International Journal of Pharmaceutics. 2001 April 17; 217(1-2): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292555&dopt=Abstract
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Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. Author(s): Issioui T, Klein KW, White PF, Watcha MF, Skrivanek GD, Jones SB, Hu J, Marple BF, Ing C. Source: Anesthesiology. 2002 October; 97(4): 931-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357161&dopt=Abstract
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Costs and effectiveness of rofecoxib, celecoxib, and acetaminophen for preventing pain after ambulatory otolaryngologic surgery. Author(s): Watcha MF, Issioui T, Klein KW, White PF. Source: Anesthesia and Analgesia. 2003 April; 96(4): 987-94, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651647&dopt=Abstract
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COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Author(s): Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 15; 99(21): 13926-31. Epub 2002 September 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242329&dopt=Abstract
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CSF Glucose Concentrations in Infants with Febrile Convulsions and the Possible Effect of Acetaminophen. Author(s): Mohammadi M, Mohebbi MR, Naderi F. Source: Indian Pediatrics. 2003 December; 40(12): 1183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14722369&dopt=Abstract
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Deafness associated with abuse of hydrocodone/acetaminophen. Author(s): Oh AK, Ishiyama A, Baloh RW. Source: Neurology. 2000 June 27; 54(12): 2345. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881270&dopt=Abstract
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Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure. Author(s): Doering CB, Parker ET, Nichols CE, Lollar P. Source: Blood. 2003 September 1; 102(5): 1743-4. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730105&dopt=Abstract
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Delayed increase in acetaminophen concentration after Tylenol PM overdose. Author(s): Ho SY, Arellano M, Zolkowski-Wynne J. Source: The American Journal of Emergency Medicine. 1999 May; 17(3): 315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10337903&dopt=Abstract
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Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population. Author(s): Rahme E, Pettitt D, LeLorier J. Source: Arthritis and Rheumatism. 2002 November; 46(11): 3046-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428249&dopt=Abstract
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Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H(2) synthases. Author(s): Boutaud O, Aronoff DM, Richardson JH, Marnett LJ, Oates JA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 May 14; 99(10): 7130-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011469&dopt=Abstract
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Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection. Author(s): Muldrew KL, James LP, Coop L, McCullough SS, Hendrickson HP, Hinson JA, Mayeux PR. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 April; 30(4): 446-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901099&dopt=Abstract
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Determination of paracetamol (acetaminophen) in different body fluids and organ samples after solid-phase extraction using HPLC and an immunological method. Author(s): Pufal E, Sykutera M, Rochholz G, Schutz HW, Sliwka K, Kaatsch HJ. Source: Fresenius' Journal of Analytical Chemistry. 2000 July; 367(6): 596-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225839&dopt=Abstract
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Development of oral acetaminophen chewable tablets with inhibited bitter taste. Author(s): Suzuki H, Onishi H, Takahashi Y, Iwata M, Machida Y. Source: International Journal of Pharmaceutics. 2003 January 30; 251(1-2): 123-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527182&dopt=Abstract
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Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients. Author(s): Romsing J, Ostergaard D, Drozdziewicz D, Schultz P, Ravn G. Source: Acta Anaesthesiologica Scandinavica. 2000 March; 44(3): 291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714842&dopt=Abstract
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Did sevoflurane contribute to hepatic failure in a child given large doses of acetaminophen? Author(s): Siddiqui MS, Vollers JM, Mayhew JF. Source: Anesthesia and Analgesia. 2002 July; 95(1): 253; Author Reply 253-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088983&dopt=Abstract
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Does acetaminophen affect liver function in alcoholic patients? Author(s): Saseen JJ. Source: The Journal of Family Practice. 2003 March; 52(3): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620167&dopt=Abstract
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Early pregnancy termination with vaginal misoprostol combined with loperamide and acetaminophen prophylaxis. Author(s): Jain JK, Harwood B, Meckstroth KR, Mishell DR. Source: Contraception. 2001 April; 63(4): 217-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376649&dopt=Abstract
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Effect of acetaminophen on atherosclerosis. Author(s): Chong PH, Kezele B, Pontikes PJ. Source: The Annals of Pharmacotherapy. 2001 November; 35(11): 1476-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724102&dopt=Abstract
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Effect of acetaminophen on the accuracy of glucose measurements obtained with the GlucoWatch biographer. Author(s): Tierney MJ, Garg S, Ackerman NR, Fermi SJ, Kennedy J, Lopatin M, Potts RO, Tamada JA. Source: Diabetes Technology & Therapeutics. 2000 Summer; 2(2): 199-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469259&dopt=Abstract
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Effect of acetaminophen on the myeloperoxidase-hydrogen peroxide-nitrite mediated oxidation of LDL. Author(s): Chou TM, Greenspan P. Source: Biochimica Et Biophysica Acta. 2002 March 15; 1581(1-2): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960752&dopt=Abstract
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Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Author(s): Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 March; 282(3): E551-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832356&dopt=Abstract
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Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial. Author(s): Kuffner EK, Dart RC, Bogdan GM, Hill RE, Casper E, Darton L. Source: Archives of Internal Medicine. 2001 October 8; 161(18): 2247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575982&dopt=Abstract
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Effect of multifaceted intervention promoting early switch from intravenous to oral acetaminophen for postoperative pain: controlled, prospective, before and after study. Author(s): Ripouteau C, Conort O, Lamas JP, Auleley GR, Hazebroucq G, Durieux P. Source: Bmj (Clinical Research Ed.). 2000 December 9; 321(7274): 1460-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110743&dopt=Abstract
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Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial. Author(s): Dippel DW, van Breda EJ, van Gemert HM, van der Worp HB, Meijer RJ, Kappelle LJ, Koudstaal PJ. Source: Stroke; a Journal of Cerebral Circulation. 2001 July; 32(7): 1607-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441208&dopt=Abstract
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Effectiveness and safety of new oxycodone/acetaminophen formulations with reduced acetaminophen for the treatment of low back pain. Author(s): Gammaitoni AR, Galer BS, Lacouture P, Domingos J, Schlagheck T. Source: Pain Medicine (Malden, Mass.). 2003 March; 4(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873275&dopt=Abstract
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Effectiveness of delayed activated charcoal administration in simulated paracetamol (acetaminophen) overdose. Author(s): Yeates PJ, Thomas SH. Source: British Journal of Clinical Pharmacology. 2000 January; 49(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606832&dopt=Abstract
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Effectiveness of pseudoephedrine plus acetaminophen for treatment of symptoms attributed to the paranasal sinuses associated with the common cold. Author(s): Sperber SJ, Turner RB, Sorrentino JV, O'Connor RR, Rogers J, Gwaltney JM Jr. Source: Archives of Family Medicine. 2000 November-December; 9(10): 979-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115196&dopt=Abstract
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Effects of acetaminophen administration to patients in intensive care. Author(s): Mackenzie I, Forrest K, Thompson F, Marsh R. Source: Intensive Care Medicine. 2000 September; 26(9): 1408. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089781&dopt=Abstract
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Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells. Author(s): Sciulli MG, Seta F, Tacconelli S, Capone ML, Ricciotti E, Pistritto G, Patrignani P. Source: British Journal of Pharmacology. 2003 February; 138(4): 634-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598417&dopt=Abstract
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Effects of short-term use of ibuprofen or acetaminophen on bone resorption in healthy men: a double-blind, placebo-controlled pilot study. Author(s): Head JE, Bryant BJ, Grills BL, Ebeling PR. Source: Bone. 2001 November; 29(5): 437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704495&dopt=Abstract
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Efficacy and safety of acetaminophen and naproxen in the treatment of tension-type headache. A randomized, double-blind, placebo-controlled trial. Author(s): Prior MJ, Cooper KM, May LG, Bowen DL. Source: Cephalalgia : an International Journal of Headache. 2002 November; 22(9): 740-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421160&dopt=Abstract
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Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study. Author(s): Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M. Source: Archives of Internal Medicine. 2000 December 11-25; 160(22): 3486-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112243&dopt=Abstract
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Efficacy and safety of clemastine-pseudoephedrine-acetaminophen versus pseudoephedrine-acetaminophen in the treatment of seasonal allergic rhinitis in a 1day, placebo-controlled park study. Author(s): Meltzer EO, Casale TB, Gold MS, O'Connor R, Reitberg D, del Rio E, Weiler JM, Weiler K. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 January; 90(1): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546342&dopt=Abstract
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Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Author(s): Gimbel JS, Brugger A, Zhao W, Verburg KM, Geis GS. Source: Clinical Therapeutics. 2001 February; 23(2): 228-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293556&dopt=Abstract
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Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial. Author(s): Geba GP, Weaver AL, Polis AB, Dixon ME, Schnitzer TJ; Vioxx, Acetaminophen, Celecoxib Trial (VACT) Group. Source: Jama : the Journal of the American Medical Association. 2002 January 2; 287(1): 64-71. Erratum In: Jama 2002 February 27; 287(8): 989. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754710&dopt=Abstract
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Efficacy of superactivated charcoal administered late (3 hours) after acetaminophen overdose. Author(s): Sato RL, Wong JJ, Sumida SM, Marn RY, Enoki NR, Yamamoto LG. Source: The American Journal of Emergency Medicine. 2003 May; 21(3): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811710&dopt=Abstract
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Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents. Author(s): James LP, Farrar HC, Darville TL, Sullivan JE, Givens TG, Kearns GL, Wasserman GS, Simpson PM, Hinson JA; Pediatric Pharmacology Research Unit Network, National Institute of Child Health and Human Development. Source: Clinical Pharmacology and Therapeutics. 2001 September; 70(3): 280-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557916&dopt=Abstract
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Endotoxin-induced activation of the coagulation cascade in humans: effect of acetylsalicylic acid and acetaminophen. Author(s): Pernerstorfer T, Stohlawetz P, Hollenstein U, Dzirlo L, Eichler HG, Kapiotis S, Jilma B, Speiser W. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 October; 19(10): 251723. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521382&dopt=Abstract
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Energy expenditure in acetaminophen-induced fulminant hepatic failure. Author(s): Walsh TS, Wigmore SJ, Hopton P, Richardson R, Lee A. Source: Critical Care Medicine. 2000 March; 28(3): 649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10752809&dopt=Abstract
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Enhanced acetaminophen hepatotoxicity in transgenic mice overexpressing BCL-2. Author(s): Adams ML, Pierce RH, Vail ME, White CC, Tonge RP, Kavanagh TJ, Fausto N, Nelson SD, Bruschi SA. Source: Molecular Pharmacology. 2001 November; 60(5): 907-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11641418&dopt=Abstract
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Enzymatic shunting: resolving the acetaminophen-warfarin controversy. Author(s): Lehmann DE. Source: Pharmacotherapy. 2000 December; 20(12): 1464-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130219&dopt=Abstract
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Et tu, acetaminophen? Author(s): Abramson SB. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2831-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428221&dopt=Abstract
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Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Author(s): Thummel KE, Slattery JT, Ro H, Chien JY, Nelson SD, Lown KE, Watkins PB. Source: Clinical Pharmacology and Therapeutics. 2000 June; 67(6): 591-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10872641&dopt=Abstract
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Evaluation of occult acetaminophen hepatotoxicity in hospitalized children receiving acetaminophen. Pediatric Pharmacology Research Unit Network. Author(s): James LP, Wilson JT, Simar R, Farrar HC, Kearns GL, Simpson PM, Hinson JA, Pumford NR; Pediatric Pharmacology Research Unit Network. Source: Clinical Pediatrics. 2001 May; 40(5): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388672&dopt=Abstract
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Experience with liver dialysis in acetaminophen induced fulminant hepatic failure: a preliminary report. Author(s): Akdogan M, El-Sahwi K, Ahmed U, Rashwan S, Sebastian A, Wright H, Nour B, Gurakar A. Source: Turk J Gastroenterol. 2003 September; 14(3): 164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14655058&dopt=Abstract
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False-positive acetaminophen results in a hyperbilirubinemic patient. Author(s): Bertholf RL, Johannsen LM, Bazooband A, Mansouri V. Source: Clinical Chemistry. 2003 April; 49(4): 695-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651837&dopt=Abstract
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False-positive acetaminophen results in hyperbilirubinemic patients with an enzymatic colorimetric assay. Author(s): Stolk LM, Nelissen B, van der Heijden J. Source: Pharmacy World & Science : Pws. 2003 October; 25(5): 242. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14584232&dopt=Abstract
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Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy. EuroMap Study Group. Author(s): Thulstrup AM, Sorensen HT, Nielsen GL, Andersen L, Barrett D, Vilstrup H, Olsen J. Source: American Journal of Perinatology. 1999; 16(7): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10614698&dopt=Abstract
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Frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin in US women. Author(s): Curhan GC, Bullock AJ, Hankinson SE, Willett WC, Speizer FE, Stampfer MJ. Source: Pharmacoepidemiology and Drug Safety. 2002 December; 11(8): 687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512245&dopt=Abstract
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Fulminant hepatic failure due to acetaminophen poisoning may be less common in Hong Kong. Author(s): Chan TY. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(2): 175-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407506&dopt=Abstract
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Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Author(s): Bailey B, Amre DK, Gaudreault P. Source: Critical Care Medicine. 2003 January; 31(1): 299-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545033&dopt=Abstract
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Fulminant liver failure in a young child following repeated acetaminophen overdosing. Author(s): Bauer M, Babel B, Giesen H, Patzelt D. Source: J Forensic Sci. 1999 November; 44(6): 1299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10582371&dopt=Abstract
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Gastrointestinal health care resource use and costs associated with nonsteroidal antiinflammatory drugs versus acetaminophen: retrospective cohort study of an elderly population. Author(s): Rahme E, Joseph L, Kong SX, Watson DJ, LeLorier J. Source: Arthritis and Rheumatism. 2000 April; 43(4): 917-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10765939&dopt=Abstract
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Gemtuzumab Ozogamicin (Mylotarg) and hepatic veno-occlusive disease: take two acetaminophen, and. Author(s): Gordon LI. Source: Bone Marrow Transplantation. 2001 November; 28(9): 811-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781639&dopt=Abstract
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Glucuronidation of acetaminophen catalyzed by multiple rat phenol UDPglucuronosyltransferases. Author(s): Kessler FK, Kessler MR, Auyeung DJ, Ritter JK. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 March; 30(3): 324-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854153&dopt=Abstract
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Hemodialysis as adjunctive therapy for severe acetaminophen poisoning: a case report. Author(s): Wu ML, Tsai WJ, Deng JF, Yang CC. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1999 December; 62(12): 907-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634007&dopt=Abstract
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Hemolysis as a potential complication of acetaminophen overdose in a patient with glucose-6-phosphate dehydrogenase deficiency. Author(s): Sklar GE. Source: Pharmacotherapy. 2002 May; 22(5): 656-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013368&dopt=Abstract
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Hemolytic anemia after acetaminophen overdose in patient with glucose-6-phosphate dehydrogenase deficiency. Author(s): Ruha AM, Seldem B. Source: The American Journal of Medicine. 2001 February 15; 110(3): 240-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221636&dopt=Abstract
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Hepatic failure after rectal acetaminophen. Author(s): Reddy MS, Srinivas P. Source: Anesthesia and Analgesia. 2002 February; 94(2): 476. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812726&dopt=Abstract
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Hepatic failure and encephalopathy attributed to an interaction between acetaminophen and rifampicin. Author(s): Stephenson I, Qualie M, Wiselka MJ. Source: The American Journal of Gastroenterology. 2001 April; 96(4): 1310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316203&dopt=Abstract
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Hepatic failure in a child after acetaminophen and sevoflurane exposure. Author(s): Bruun LS, Elkjaer S, Bitsch-Larsen D, Andersen O. Source: Anesthesia and Analgesia. 2001 June; 92(6): 1446-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375824&dopt=Abstract
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Hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors. Author(s): Bolesta S, Haber SL. Source: The Annals of Pharmacotherapy. 2002 February; 36(2): 331-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847957&dopt=Abstract
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High altitude headache: efficacy of acetaminophen vs. ibuprofen in a randomized, controlled trial. Author(s): Harris NS, Wenzel RP, Thomas SH. Source: The Journal of Emergency Medicine. 2003 May; 24(4): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745039&dopt=Abstract
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High-dose rectal and oral acetaminophen in postoperative patients--serum and saliva concentrations. Author(s): Hahn TW, Mogensen T, Lund C, Schouenborg L, Rasmussen M. Source: Acta Anaesthesiologica Scandinavica. 2000 March; 44(3): 302-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714844&dopt=Abstract
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High-performance liquid chromatographic assay for acetaminophen glucuronide in human liver microsomes. Author(s): Alkharfy KM, Frye RF. Source: J Chromatogr B Biomed Sci Appl. 2001 April 5; 753(2): 303-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334344&dopt=Abstract
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Ibuprofen and acetaminophen: effect on muscle inflammation after eccentric exercise. Author(s): Peterson JM, Trappe TA, Mylona E, White F, Lambert CP, Evans WJ, Pizza FX. Source: Medicine and Science in Sports and Exercise. 2003 June; 35(6): 892-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783034&dopt=Abstract
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Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial. Author(s): Peter EA, Janssen PA, Grange CS, Douglas MJ. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 October 30; 165(9): 1203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706909&dopt=Abstract
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Immune thrombocytopenia resulting from sensitivity to metabolites of naproxen and acetaminophen. Author(s): Bougie D, Aster R. Source: Blood. 2001 June 15; 97(12): 3846-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389025&dopt=Abstract
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Important role of prodromal viral infections responsible for inhibition of xenobiotic metabolizing enzymes in the pathomechanism of idiopathic Reye's syndrome, Stevens-Johnson syndrome, autoimmune hepatitis, and hepatotoxicity of the therapeutic doses of acetaminophen used in genetically predisposed persons. Author(s): Prandota J. Source: American Journal of Therapeutics. 2002 March-April; 9(2): 149-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897929&dopt=Abstract
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In utero ductal closure following near-term maternal self-medication with nimesulide and acetaminophen. Author(s): Simbi KA, Secchieri S, Rinaldo M, Demi M, Zanardo V. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 July; 22(4): 440-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521476&dopt=Abstract
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Index of suspicion. Case 3. Acetaminophen overdose. Author(s): Isaacson J. Source: Pediatrics in Review / American Academy of Pediatrics. 1999 September; 20(9): 309-10, 312-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11012396&dopt=Abstract
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Influence of acute and chronic alcohol intake on the clinical course and outcome in acetaminophen overdose. Author(s): Schiodt FV, Lee WM, Bondesen S, Ott P, Christensen E. Source: Alimentary Pharmacology & Therapeutics. 2002 April; 16(4): 707-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929388&dopt=Abstract
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Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites. Author(s): Senter PD, Al-Abed Y, Metz CN, Benigni F, Mitchell RA, Chesney J, Han J, Gartner CG, Nelson SD, Todaro GJ, Bucala R. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 January 8; 99(1): 144-9. Epub 2002 Jan 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773615&dopt=Abstract
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Inhibitory effect of sorbitol on acetaminophen adsorption by activated carbon. Author(s): Nakamura T, Oida Y, Matsumoto K, Kawasaki N, Tanada S. Source: Journal of Environmental Science and Health. Part A, Toxic/Hazardous Substances & Environmental Engineering. 2002; 37(5): 905-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049124&dopt=Abstract
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Initial and subsequent dosing of rectal acetaminophen in children: a 24-hour pharmacokinetic study of new dose recommendations. Author(s): Birmingham PK, Tobin MJ, Fisher DM, Henthorn TK, Hall SC, Cote CJ. Source: Anesthesiology. 2001 March; 94(3): 385-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374595&dopt=Abstract
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Integrated pharmacokinetic-pharmacodynamic model for acetaminophen, ibuprofen, and placebo antipyresis in children. Author(s): Brown RD, Kearns GL, Wilson JT. Source: Journal of Pharmacokinetics and Biopharmaceutics. 1998 October; 26(5): 559-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205771&dopt=Abstract
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Interaction between N-acetylcysteine and activated charcoal: implications for the treatment of acetaminophen poisoning. Author(s): Tenenbein PK, Sitar DS, Tenenbein M. Source: Pharmacotherapy. 2001 November; 21(11): 1331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714205&dopt=Abstract
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Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. Author(s): Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 December; 299(3): 998-1006. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714888&dopt=Abstract
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Interventions for paracetamol (acetaminophen) overdoses. Author(s): Brok J, Buckley N, Gluud C. Source: Cochrane Database Syst Rev. 2002; (3): Cd003328. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137690&dopt=Abstract
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Investigation of the interaction between argatroban and acetaminophen, lidocaine, or digoxin. Author(s): Inglis AM, Sheth SB, Hursting MJ, Tenero DM, Graham AM, DiCicco RA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 July 1; 59(13): 1258-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116891&dopt=Abstract
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Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen. Author(s): Dong H, Haining RL, Thummel KE, Rettie AE, Nelson SD. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 December; 28(12): 1397-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095574&dopt=Abstract
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Is acetaminophen really safe in alcoholic patients? Author(s): Soll AH, Sees KL. Source: Archives of Internal Medicine. 2002 May 27; 162(10): 1194. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020194&dopt=Abstract
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Is chronic poisoning with acetaminophen in children a frequent occurrence in Toronto? Author(s): Bailey B, Lalkin A, Kapur BM, Koren G. Source: Can J Clin Pharmacol. 2001 Summer; 8(2): 96-101. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493938&dopt=Abstract
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Is continuous veno-venous hemofiltration for acetaminophen-induced acute liver and renal failure worthwhile? Author(s): Agarwal R, Farber MO. Source: Clinical Nephrology. 2002 February; 57(2): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863129&dopt=Abstract
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Ketoprofen 75 mg qid versus acetaminophen 1000 mg qid for 3 days on swelling, pain, and other postoperative events after third-molar surgery. Author(s): Bjornsson GA, Haanaes HR, Skoglund LA. Source: Journal of Clinical Pharmacology. 2003 March; 43(3): 305-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638400&dopt=Abstract
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Ketoprofen, acetaminophen, and placebo in the treatment of tension headache. Author(s): Mehlisch DR, Weaver M, Fladung B. Source: Headache. 1998 September; 38(8): 579-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398300&dopt=Abstract
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Ketorolac versus acetaminophen for treatment of acute fever in the emergency department. Author(s): Houry D, Ernst A, Weiss S, Ledbetter M. Source: Southern Medical Journal. 1999 December; 92(12): 1171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10624908&dopt=Abstract
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Knowledge about acetaminophen toxicity among emergency department visitors. Author(s): Chen L, Schneider S, Wax P. Source: Vet Hum Toxicol. 2002 December; 44(6): 370-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458645&dopt=Abstract
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Lack of effect of physical exercise on pharmacokinetics of acetaminophen tablets in healthy subjects. Author(s): Loniewski I, Sawrymowicz M, Pawlik A, Wojcicki J, Drozdzik M. Source: Acta Pol Pharm. 2001 March-April; 58(2): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501793&dopt=Abstract
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Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium. Author(s): Case JP, Baliunas AJ, Block JA. Source: Archives of Internal Medicine. 2003 January 27; 163(2): 169-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546607&dopt=Abstract
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Large dose acetaminophen reconsidered. Author(s): Dopfmer UR, Beck DH, Schenk MR, Kox WJ. Source: British Journal of Anaesthesia. 2002 May; 88(5): 744; Author Reply 744-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067026&dopt=Abstract
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Long-chain hydroxydicarboxylic aciduria, carnitine depletion and acetaminophen exposure. Author(s): Nowaczyk MJ, Whelan D, Hill RE, Clarke JT, Pollitt RJ. Source: Journal of Inherited Metabolic Disease. 2000 March; 23(2): 188-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801061&dopt=Abstract
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Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses. Author(s): James LP, Farrar HC, Sullivan JE, Givens TG, Kearns GL, Wasserman GS, Walson PD, Hinson JA, Pumford NR; Pediatric Pharmacology Research Unit Network, NICHD. Source: Journal of Clinical Pharmacology. 2001 August; 41(8): 846-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504272&dopt=Abstract
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Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Author(s): Ouellet M, Percival MD. Source: Archives of Biochemistry and Biophysics. 2001 March 15; 387(2): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370851&dopt=Abstract
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Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Author(s): Botting RM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 October; 31 Suppl 5: S202-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113024&dopt=Abstract
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Medical fortune-telling: predicting acetaminophen toxicity. Author(s): Donovan JW. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1999 November; 6(11): 1079-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569376&dopt=Abstract
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Metabolic acidosis and coma after acetaminophen ingestion. Author(s): Al-Jubouri MA. Source: Annals of Emergency Medicine. 1999 November; 34(5): 685. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577289&dopt=Abstract
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Metabolic acidosis and coma following a severe acetaminophen overdose. Author(s): Koulouris Z, Tierney MG, Jones G. Source: The Annals of Pharmacotherapy. 1999 November; 33(11): 1191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10573319&dopt=Abstract
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Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Author(s): Zhang J, Huang W, Chua SS, Wei P, Moore DD. Source: Science. 2002 October 11; 298(5592): 422-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376703&dopt=Abstract
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Modulation of serum growth factor signal transduction in Hepa 1-6 cells by acetaminophen: an inhibition of c-myc expression, NF-kappaB activation, and Raf-1 kinase activity. Author(s): Boulares HA, Giardina C, Navarro CL, Khairallah EA, Cohen SD. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 1999 April; 48(2): 264-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10353317&dopt=Abstract
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More on interference of N-acetylcysteine in measurement of acetaminophen. Author(s): Tyhach RJ. Source: Clinical Chemistry. 1999 April; 45(4): 584-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10206774&dopt=Abstract
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Morphine-sparing effect of acetaminophen in pediatric day-case surgery. Author(s): Korpela R, Korvenoja P, Meretoja OA. Source: Anesthesiology. 1999 August; 91(2): 442-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10443608&dopt=Abstract
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Multiple fixed drug eruption caused by acetaminophen. Author(s): Hayashi H, Shimizu T, Shimizu H. Source: Clinical and Experimental Dermatology. 2003 July; 28(4): 455-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823320&dopt=Abstract
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Multiple-dose pharmacokinetics of rectally administered acetaminophen in term infants. Author(s): van Lingen RA, Deinum HT, Quak CM, Okken A, Tibboel D. Source: Clinical Pharmacology and Therapeutics. 1999 November; 66(5): 509-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10579478&dopt=Abstract
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N-acetylcysteine overdosage after insignificant acetaminophen intake. Author(s): Lorentzen H, Glenthoj J, Olesen T. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(8): 984-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222729&dopt=Abstract
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Naproxen 500 mg bid versus acetaminophen 1000 mg qid: effect on swelling and other acute postoperative events after bilateral third molar surgery. Author(s): Bjornsson GA, Haanaes HR, Skoglund LA. Source: Journal of Clinical Pharmacology. 2003 August; 43(8): 849-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953342&dopt=Abstract
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Nephrotoxicity after acute severe acetaminophen poisoning in adolescents. Author(s): Boutis K, Shannon M. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(5): 441-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545233&dopt=Abstract
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New perspectives on acetaminophen and alcohol use. Author(s): Kuffner EK. Source: Am J Manag Care. 2001 December; 7(19 Suppl): S590-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11776480&dopt=Abstract
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New reports on dental analgesics. NSAIDs and cardiovascular effects, celecoxib for dental pain, and a new analgesic--tramadol with acetaminophen. Author(s): Wynn RL. Source: Gen Dent. 2002 May-June; 50(3): 218-20, 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116507&dopt=Abstract
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Nitrating reactive nitric oxygen species transform acetaminophen to 3nitroacetaminophen. Author(s): Lakshmi VM, Hsu FF, Davis BB, Zenser TV. Source: Chemical Research in Toxicology. 2000 September; 13(9): 891-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10995262&dopt=Abstract
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Nitric oxide releasing acetaminophen (nitroacetaminophen). Author(s): Moore PK, Marshall M. Source: Dig Liver Dis. 2003 May; 35 Suppl 2: S49-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846444&dopt=Abstract
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Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever. Author(s): Simmons DL, Wagner D, Westover K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 October; 31 Suppl 5: S211-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113025&dopt=Abstract
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Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain. Author(s): Olson NZ, Otero AM, Marrero I, Tirado S, Cooper S, Doyle G, Jayawardena S, Sunshine A. Source: Journal of Clinical Pharmacology. 2001 November; 41(11): 1238-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697757&dopt=Abstract
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Opioid-free analgesia following total knee arthroplasty--a multimodal approach using continuous lumbar plexus (psoas compartment) block, acetaminophen, and ketorolac. Author(s): Horlocker TT, Hebl JR, Kinney MA, Cabanela ME. Source: Regional Anesthesia and Pain Medicine. 2002 January-February; 27(1): 105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799514&dopt=Abstract
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Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning? Author(s): Buckley NA, Whyte IM, O'Connell DL, Dawson AH. Source: Journal of Toxicology. Clinical Toxicology. 1999; 37(6): 759-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584588&dopt=Abstract
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Oxidative stress and redox imbalance in acetaminophen toxicity. Author(s): Masutani H. Source: The Pharmacogenomics Journal. 2001; 1(3): 165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908750&dopt=Abstract
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Pancytopenia, hyperglycemia, shock, coma, rhabdomyolysis, and pancreatitis associated with acetaminophen poisoning. Author(s): Yang CC, Deng JF, Lin TJ. Source: Vet Hum Toxicol. 2001 December; 43(6): 344-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757993&dopt=Abstract
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Paracetamol (acetaminophen) hypersensitivity. Author(s): de Paramo BJ, Gancedo SQ, Cuevas M, Camo IP, Martin JA, Cosmes EL. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2000 December; 85(6 Pt 1): 508-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152174&dopt=Abstract
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Paracetamol (acetaminophen) poisoning. Author(s): Buckley N, Eddleston M. Source: Clin Evid. 2002 June; (7): 1263-9. Review. No Abstract Available. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230744&dopt=Abstract
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Paracetamol (acetaminophen) poisoning: report of two cases. Author(s): Singh S, Hariram V, Jain S, Singh K. Source: J Assoc Physicians India. 2000 September; 48(9): 938. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198805&dopt=Abstract
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Parental knowledge of different acetaminophen concentrations for infants and children. Author(s): Barrett TW, Norton VC. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2000 June; 7(6): 718-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905654&dopt=Abstract
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Patients discharged with a prescription for acetaminophen-containing narcotic analgesics do not receive appropriate written instructions. Author(s): Osborne ZP, Bryant SM. Source: The American Journal of Emergency Medicine. 2003 January; 21(1): 48-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563581&dopt=Abstract
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Pediatric acetaminophen overdose. Author(s): Isbister G, Whyte I, Dawson A. Source: Journal of Toxicology. Clinical Toxicology. 2001; 39(2): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407504&dopt=Abstract
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Pediatric acetaminophen overdose: risk factors associated with hepatocellular injury. Author(s): Alander SW, Dowd MD, Bratton SL, Kearns GL. Source: Archives of Pediatrics & Adolescent Medicine. 2000 April; 154(4): 346-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10768670&dopt=Abstract
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Pediatric acetaminophen poisoning. Author(s): Isbister G, Whyte I, Dawson A. Source: Archives of Pediatrics & Adolescent Medicine. 2001 March; 155(3): 417-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231816&dopt=Abstract
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Persistently elevated acetaminophen concentrations for two days after an initial fourhour non-toxic concentration. Author(s): Spiller HA. Source: Vet Hum Toxicol. 2001 August; 43(4): 218-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474737&dopt=Abstract
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Pharmacokinetic interaction between acetaminophen and lansoprazole. Author(s): Sanaka M, Kuyama Y, Mineshita S, Qi J, Hanada Y, Enatsu I, Tanaka H, Makino H, Yamanaka M. Source: Journal of Clinical Gastroenterology. 1999 July; 29(1): 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405233&dopt=Abstract
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Pharmacokinetics of acetaminophen and ibuprofen when coadministered with telmisartan in healthy volunteers. Author(s): Stangier J, Su CA, Fraunhofer A, Tetzloff W. Source: Journal of Clinical Pharmacology. 2000 December; 40(12 Pt 1): 1338-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11185632&dopt=Abstract
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Pharmacokinetics of acetaminophen in Hong Kong Chinese subjects. Author(s): Yin OQ, Tomlinson B, Chow AH, Chow MS. Source: International Journal of Pharmaceutics. 2001 July 17; 222(2): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427360&dopt=Abstract
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Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery. Author(s): Romsing J, Ostergaard D, Senderovitz T, Drozdziewicz D, Sonne J, Ravn G. Source: Paediatric Anaesthesia. 2001 March; 11(2): 205-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240880&dopt=Abstract
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Phenytoin as a possible cause of acetaminophen hepatotoxicity: case report and review of the literature. Author(s): Brackett CC, Bloch JD. Source: Pharmacotherapy. 2000 February; 20(2): 229-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10678302&dopt=Abstract
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Population-based incidence and outcome of acetaminophen poisoning by type of ingestion. Author(s): Bond GR, Hite LK. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1999 November; 6(11): 1115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569383&dopt=Abstract
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Potential danger from too much acetaminophen in opiate agonist combination products. Author(s): Armstrong TA, Rohal GM. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 September 1; 56(17): 1774-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512512&dopt=Abstract
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Potentiation of the acenocoumarol anticoagulant effect by acetaminophen. Author(s): Bagheri H, Bernhard NB, Montastruc JL. Source: The Annals of Pharmacotherapy. 1999 April; 33(4): 506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332548&dopt=Abstract
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Predicting concentrations in children presenting with acetaminophen overdose. Author(s): Anderson BJ, Holford NH, Armishaw JC, Aicken R. Source: The Journal of Pediatrics. 1999 September; 135(3): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10484791&dopt=Abstract
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Predictive ability of level A in vitro-in vivo correlation for ringcap controlled-release acetaminophen tablets. Author(s): Dalton JT, Straughn AB, Dickason DA, Grandolfi GP. Source: Pharmaceutical Research. 2001 December; 18(12): 1729-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785693&dopt=Abstract
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Predictive properties of a qualitative urine acetaminophen screen in patients with self-poisoning. Author(s): Perrone J, Hollander JE, Shaw L, De Roos F. Source: Journal of Toxicology. Clinical Toxicology. 1999; 37(6): 769-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584589&dopt=Abstract
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Predictors of outcome after acetaminophen poisoning in children and adolescents. Author(s): James LP, Wells E, Beard RH, Farrar HC. Source: The Journal of Pediatrics. 2002 May; 140(5): 522-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032516&dopt=Abstract
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Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1,799 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia. Author(s): Wolfe F, Zhao S, Lane N. Source: Arthritis and Rheumatism. 2000 February; 43(2): 378-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10693878&dopt=Abstract
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Preference for nonsteroidal antiinflammatory drugs versus acetaminophen and concomitant use of both types of drugs in patients with osteoarthritis. Author(s): Pincus T, Swearingen C, Cummins P, Callahan LF. Source: The Journal of Rheumatology. 2000 April; 27(4): 1020-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10782831&dopt=Abstract
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Profound hearing loss associated with hydrocodone/acetaminophen abuse. Author(s): Friedman RA, House JW, Luxford WM, Gherini S, Mills D. Source: The American Journal of Otology. 2000 March; 21(2): 188-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733182&dopt=Abstract
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Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study. Author(s): Koennecke HC, Leistner S. Source: Neurology. 2001 December 26; 57(12): 2301-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756615&dopt=Abstract
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Prophylactically-administered rectal acetaminophen does not reduce postoperative opioid requirements in infants and small children undergoing elective cleft palate repair. Author(s): Bremerich DH, Neidhart G, Heimann K, Kessler P, Behne M. Source: Anesthesia and Analgesia. 2001 April; 92(4): 907-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273923&dopt=Abstract
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Prospective evaluation of mild to moderate pediatric acetaminophen exposures. Author(s): Mohler CR, Nordt SP, Williams SR, Manoguerra AS, Clark RF. Source: Annals of Emergency Medicine. 2000 March; 35(3): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692190&dopt=Abstract
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Protective effect of chlormethiazole, a sedative, against acetaminophen-induced liver injury in mice. Author(s): Lee HC, Jung SA, Jung HK, Yi SY, Kim DY, Moon IH, Park SS. Source: Korean J Intern Med. 1999 July; 14(2): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10461422&dopt=Abstract
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Protective effect of moutan cortex extract on acetaminophen-induced cytotoxicity in human Chang liver cells. Author(s): Shon YH, Nam KS. Source: Biological & Pharmaceutical Bulletin. 2002 November; 25(11): 1427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419953&dopt=Abstract
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Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen. Author(s): Roden M, Raffesberg W, Raber W, Bernroider E, Niederle B, Waldhausl W, Gasic S. Source: Clinical Chemistry. 2001 June; 47(6): 1061-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375292&dopt=Abstract
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Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Author(s): Gammaitoni AR, Galer BS, Bulloch S, Lacouture P, Caruso F, Ma T, Schlagheck T. Source: Journal of Clinical Pharmacology. 2003 March; 43(3): 296-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638399&dopt=Abstract
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Rapid liquid chromatographic assay for the determination of acetaminophen in plasma after propacetamol administration: application to pharmacokinetic studies. Author(s): Campanero MA, Calahorra B, Garcia-Quetglas E, Lopez-Ocariz A, Honorato J. Source: Journal of Pharmaceutical and Biomedical Analysis. 1999 June; 20(1-2): 327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704039&dopt=Abstract
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Rates of serious gastrointestinal events from low dose use of acetylsalicylic acid, acetaminophen, and ibuprofen in patients with osteoarthritis and rheumatoid arthritis. Author(s): Fries JF, Bruce B. Source: The Journal of Rheumatology. 2003 October; 30(10): 2226-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528521&dopt=Abstract
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Rectal and oral acetaminophen. Author(s): Beck DH, Schenk MR, Kastrup M, Schoeffel C, Kox WJ. Source: Acta Anaesthesiologica Scandinavica. 2001 April; 45(4): 519. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300395&dopt=Abstract
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Reduction of toxic metabolite formation of acetaminophen. Author(s): Hazai E, Vereczkey L, Monostory K. Source: Biochemical and Biophysical Research Communications. 2002 March 8; 291(4): 1089-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866476&dopt=Abstract
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Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Author(s): Garcia Rodriguez LA, Hernandez-Diaz S. Source: Epidemiology (Cambridge, Mass.). 2001 September; 12(5): 570-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11505178&dopt=Abstract
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Renal impairment without hepatic damage after acetaminophen overdose. Author(s): Ammenti A, Ferrante R, Spagna A. Source: Pediatric Nephrology (Berlin, Germany). 1999 April; 13(3): 271-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10353422&dopt=Abstract
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Resistance of three immortalized human hepatocyte cell lines to acetaminophen and N-acetyl-p-benzoquinoneimine toxicity. Author(s): McCloskey P, Edwards RJ, Tootle R, Selden C, Roberts E, Hodgson HJ. Source: Journal of Hepatology. 1999 November; 31(5): 841-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580581&dopt=Abstract
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Risk factors for acetaminophen and nimesulide intolerance in patients with NSAIDinduced skin disorders. Author(s): Asero R. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1999 June; 82(6): 554-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10400483&dopt=Abstract
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Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a doubleblind, randomized, placebo- and active comparator-controlled clinical trial. Author(s): Chang DJ, Fricke JR, Bird SR, Bohidar NR, Dobbins TW, Geba GP. Source: Clinical Therapeutics. 2001 September; 23(9): 1446-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589259&dopt=Abstract
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Rofecoxib vs celecoxib vs acetaminophen for treatment of osteoarthritis. Author(s): Henderson P. Source: Jama : the Journal of the American Medical Association. 2002 April 10; 287(14): 1799; Author Reply 1799-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939848&dopt=Abstract
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Rofecoxib vs celecoxib vs acetaminophen for treatment of osteoarthritis. Author(s): Bierma-Zeinstra SM, Bohnen AM, Berger MY, Thomas S. Source: Jama : the Journal of the American Medical Association. 2002 April 10; 287(14): 1799; Author Reply 1799-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939847&dopt=Abstract
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Safe use of acetaminophen. Author(s): Barton KN. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 May 27; 168(11): 1390. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771057&dopt=Abstract
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Safety of childhood acetaminophen overdose. Author(s): Caravati EM. Source: Annals of Emergency Medicine. 2001 January; 37(1): 114-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145785&dopt=Abstract
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Serum phosphate as a predictor of outcome in acetaminophen-induced fulminant hepatic failure. Author(s): Gow PJ, Sood S, Angus PW. Source: Hepatology (Baltimore, Md.). 2003 March; 37(3): 711-2; Author Reply 712. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601369&dopt=Abstract
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Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Author(s): Schmidt LE, Dalhoff K. Source: Hepatology (Baltimore, Md.). 2002 September; 36(3): 659-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198658&dopt=Abstract
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Short report: parental knowledge of rectal acetaminophen. Author(s): Goldman RD, Scolnik D. Source: Can Fam Physician. 2002 September; 48: 1505-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371309&dopt=Abstract
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Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. Author(s): Woo OF, Mueller PD, Olson KR, Anderson IB, Kim SY. Source: Annals of Emergency Medicine. 2000 April; 35(4): 363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736123&dopt=Abstract
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Simultaneous determination of carisoprodol and acetaminophen in an attempted suicide by liquid chromatography-mass spectrometry with positive electrospray ionization. Author(s): Matsumoto T, Sano T, Matsuoka T, Aoki M, Maeno Y, Nagao M. Source: Journal of Analytical Toxicology. 2003 March; 27(2): 118-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670008&dopt=Abstract
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Single and multiple dose pharmacokinetics of acetaminophen (paracetamol) in polymedicated very old patients with rheumatic pain. Author(s): Bannwarth B, Pehourcq F, Lagrange F, Matoga M, Maury S, Palisson M, Le Bars M. Source: The Journal of Rheumatology. 2001 January; 28(1): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196522&dopt=Abstract
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Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain. Author(s): Collins SL, Edwards JE, Moore RA, McQuay HJ. Source: Cochrane Database Syst Rev. 2000; (2): Cd001440. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796793&dopt=Abstract
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Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. Author(s): Moore A, Collins S, Carroll D, McQuay H, Edwards J. Source: Cochrane Database Syst Rev. 2000; (2): Cd001547. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796810&dopt=Abstract
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Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions. Author(s): Ziccardi VB, Desjardins PJ, Daly-DeJoy E, Seng GF. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2000 June; 58(6): 622-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10847283&dopt=Abstract
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Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. Author(s): Trappe TA, Fluckey JD, White F, Lambert CP, Evans WJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 5067-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600586&dopt=Abstract
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Study of an anaphylactoid reaction to acetaminophen. Author(s): Liao CM, Chen WC, Lin CY. Source: Acta Paediatr Taiwan. 2002 May-June; 43(3): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148965&dopt=Abstract
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Sustained intake of paracetamol (acetaminophen) during oral anticoagulant therapy with coumarins does not cause clinically important INR changes: a randomized double-blind clinical trial. Author(s): Gadisseur AP, Van Der Meer FJ, Rosendaal FR. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 April; 1(4): 714-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871405&dopt=Abstract
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Synergetic signaling for apoptosis in vitro by ethanol and acetaminophen. Author(s): Neuman MG. Source: Alcohol (Fayetteville, N.Y.). 2002 June; 27(2): 89-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106828&dopt=Abstract
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Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen. Author(s): Clark SJ, Shojaee-Moradie F, Croos P, Seed PT, Umpleby AM, Wendon JA, Miell J. Source: Hepatology (Baltimore, Md.). 2001 July; 34(1): 109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11431740&dopt=Abstract
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Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose. Author(s): Schiodt FV, Ott P, Tygstrup N, Dahl B, Bondesen S. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2001 August; 7(8): 732-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510020&dopt=Abstract
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The accuracy of the diagnosis of suspected paracetamol (acetaminophen) hypersensitivity: results of a single-blinded trial. Author(s): Kvedariene V, Bencherioua AM, Messaad D, Godard P, Bousquet J, Demoly P. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 September; 32(9): 1366-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220477&dopt=Abstract
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The analgesic efficacy of preoperative high dose (40 mg x kg(-1)) oral acetaminophen after bilateral myringotomy and tube insertion in children. Author(s): Bolton P, Bridge HS, Montgomery CJ, Merrick PM. Source: Paediatric Anaesthesia. 2002 January; 12(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849572&dopt=Abstract
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The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery. Author(s): Daniels SE, Desjardins PJ, Talwalker S, Recker DP, Verburg KM. Source: The Journal of the American Dental Association. 2002 May; 133(5): 611-21; Quiz 625. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036167&dopt=Abstract
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The Clara cells activated by acetaminophen. Author(s): Amatya BM, Kimula Y, Koike M. Source: J Med Dent Sci. 2002 December; 49(4): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641380&dopt=Abstract
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The cost-effectiveness of acetaminophen, NSAIDs, and selective COX-2 inhibitors in the treatment of symptomatic knee osteoarthritis. Author(s): Kamath CC, Kremers HM, Vanness DJ, O'Fallon WM, Cabanela RL, Gabriel SE. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2003 March-April; 6(2): 144-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641865&dopt=Abstract
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The difficulty of risk assessment for hepatic injury associated with supra-therapeutic acetaminophen use. Author(s): Bond GR, Wiegand CB, Hite LK. Source: Vet Hum Toxicol. 2003 June; 45(3): 150-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776794&dopt=Abstract
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The effect of alcohol on acetaminophen hepatotoxicity. Author(s): Holtzman JL. Source: Archives of Internal Medicine. 2002 May 27; 162(10): 1193. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020193&dopt=Abstract
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The effect of gelatin cross-linking on the bioequivalence of hard and soft gelatin acetaminophen capsules. Author(s): Meyer MC, Straughn AB, Mhatre RM, Hussain A, Shah VP, Bottom CB, Cole ET, Lesko LL, Mallinowski H, Williams RL. Source: Pharmaceutical Research. 2000 August; 17(8): 962-6. Erratum In: Pharm Res 2001 May; 18(5): 718. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028942&dopt=Abstract
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The effects of food restriction in man on hepatic metabolism of acetaminophen. Author(s): Schenker S, Speeg KV Jr, Perez A, Finch J. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 April; 20(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11327742&dopt=Abstract
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The efficacy of premedication with celecoxib and acetaminophen in preventing pain after otolaryngologic surgery. Author(s): Issioui T, Klein KW, White PF, Watcha MF, Coloma M, Skrivanek GD, Jones SB, Thornton KC, Marple BF. Source: Anesthesia and Analgesia. 2002 May; 94(5): 1188-93, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973187&dopt=Abstract
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The intravenous use of oral acetylcysteine (mucomyst) for the treatment of acetaminophen overdose. Author(s): Amirzadeh A, McCotter C. Source: Archives of Internal Medicine. 2002 January 14; 162(1): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784228&dopt=Abstract
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The new analgesic combination tramadol/acetaminophen. Author(s): Schnitzer T. Source: European Journal of Anaesthesiology. 2003; 20 Suppl 28: 13-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785457&dopt=Abstract
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The paradoxical effect of acetaminophen on CYP3A4 activity and content in transfected HepG2 cells. Author(s): Feierman DE, Melnikov Z, Zhang J. Source: Archives of Biochemistry and Biophysics. 2002 February 1; 398(1): 109-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811955&dopt=Abstract
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The potential interaction between oral anticoagulants and acetaminophen in everyday practice. Author(s): van den Bemt PM, Geven LM, Kuitert NA, Risselada A, Brouwers JR. Source: Pharmacy World & Science : Pws. 2002 October; 24(5): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426965&dopt=Abstract
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The risk of upper gastrointestinal complications associated with nonsteroidal antiinflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Author(s): Garcia Rodriguez LA, Hernandez-Diaz S. Source: Arthritis Research. 2001; 3(2): 98-101. Epub 2000 December 15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11178116&dopt=Abstract
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The role of acetaminophen in the management of patients with osteoarthritis. Author(s): Shamoon M, Hochberg MC. Source: The American Journal of Medicine. 2001 February 19; 110 Suppl 3A: 46S-9S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173050&dopt=Abstract
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The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity. Author(s): Jaeschke H, Knight TR, Bajt ML. Source: Toxicology Letters. 2003 October 15; 144(3): 279-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927346&dopt=Abstract
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The safety of acetaminophen and ibuprofen among children younger than two years old. Author(s): Lesko SM, Mitchell AA. Source: Pediatrics. 1999 October; 104(4): E39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10506264&dopt=Abstract
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The value of plasma acetaminophen half-life in antidote-treated acetaminophen overdosage. Author(s): Schiodt FV, Ott P, Christensen E, Bondesen S. Source: Clinical Pharmacology and Therapeutics. 2002 April; 71(4): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956504&dopt=Abstract
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Timing of the effect of acetaminophen on body temperature in patients with acute ischemic stroke. Author(s): Dippel DW, van Breda EJ, van der Worp HB, van Gemert HM, Kappelle LJ, Algra A, Koudstaal PJ. Source: Neurology. 2003 September 9; 61(5): 677-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963761&dopt=Abstract
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Toxic acetaminophen doses are toxic or do you know where your acetaminophen is today? Author(s): Wolowich WR, Casavant MJ. Source: Pharmacotherapy. 2000 July; 20(7): 862. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907980&dopt=Abstract
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Toxic interaction of didanosine and acetaminophen leading to severe hepatitis and pancreatitis: a case report and review of the literature. Author(s): Lederman JC, Nawaz H. Source: The American Journal of Gastroenterology. 2001 December; 96(12): 3474-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11774996&dopt=Abstract
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Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Author(s): Bennett RM, Kamin M, Karim R, Rosenthal N. Source: The American Journal of Medicine. 2003 May; 114(7): 537-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753877&dopt=Abstract
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Tramadol and acetaminophen tablets for dental pain. Author(s): Medve RA, Wang J, Karim R. Source: Anesthesia Progress. 2001 Summer; 48(3): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724223&dopt=Abstract
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Tramadol suppositories are less suitable for post-operative pain relief than rectal acetaminophen/codeine. Author(s): Pluim MA, Wegener JT, Rupreht J, Vulto AG. Source: European Journal of Anaesthesiology. 1999 July; 16(7): 473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457880&dopt=Abstract
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Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. Author(s): Mullican WS, Lacy JR; TRAMAP-ANAG-006 Study Group. Source: Clinical Therapeutics. 2001 September; 23(9): 1429-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589258&dopt=Abstract
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Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: a multicenter, randomized, double-blind, placebo-controlled outpatient study. Author(s): Ruoff GE, Rosenthal N, Jordan D, Karim R, Kamin M; Protocol CAPSS-112 Study Group. Source: Clinical Therapeutics. 2003 April; 25(4): 1123-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809961&dopt=Abstract
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Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study. Author(s): Silverfield JC, Kamin M, Wu SC, Rosenthal N; CAPSS-105 Study Group. Source: Clinical Therapeutics. 2002 February; 24(2): 282-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911558&dopt=Abstract
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Transiently altered acetaminophen metabolism after liver transplantation. Author(s): Park JM, Lin YS, Calamia JC, Thummel KE, Slattery JT, Kalhorn TF, Carithers RL Jr, Levy AE, Marsh CL, Hebert MF. Source: Clinical Pharmacology and Therapeutics. 2003 June; 73(6): 545-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811364&dopt=Abstract
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Treatment of acetaminophen ingestion with a superactivated charcoal-cola mixture. Author(s): Rangan C, Nordt SP, Hamilton R, Ingels M, Clark RF. Source: Annals of Emergency Medicine. 2001 January; 37(1): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145772&dopt=Abstract
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Treatment of acetaminophen overdose. Author(s): Zed PJ, Krenzelok EP. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 June 1; 56(11): 1081-91; Quiz 10913. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10385455&dopt=Abstract
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Treatment of acetaminophen-induced hepatitis and fulminant hepatic failure with extracorporeal sorbent-based devices. Author(s): Ash SR, Caldwell CA, Singer GG, Lowell JA, Howard TK, Rustgi VK. Source: Adv Ren Replace Ther. 2002 January; 9(1): 42-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927906&dopt=Abstract
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Treatment of menstruation-associated migraine with the nonprescription combination of acetaminophen, aspirin, and caffeine: results from three randomized, placebo-controlled studies. Author(s): Silberstein SD, Armellino JJ, Hoffman HD, Battikha JP, Hamelsky SW, Stewart WF, Lipton RB. Source: Clinical Therapeutics. 1999 March; 21(3): 475-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10321417&dopt=Abstract
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Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial. Author(s): Caldwell JR, Hale ME, Boyd RE, Hague JM, Iwan T, Shi M, Lacouture PG. Source: The Journal of Rheumatology. 1999 April; 26(4): 862-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10229408&dopt=Abstract
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Treatment of osteoarthritis with acetaminophen: efficacy, safety, and comparison with nonsteroidal anti-inflammatory drugs. Author(s): Shamoon M, Hochberg MC. Source: Curr Rheumatol Rep. 2000 December; 2(6): 454-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11123097&dopt=Abstract
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Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic patient: a systematic review. Author(s): Dart RC, Kuffner EK, Rumack BH. Source: American Journal of Therapeutics. 2000 March; 7(2): 123-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11319580&dopt=Abstract
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Treatment of severe, disabling migraine attacks in an over-the-counter population of migraine sufferers: results from three randomized, placebo-controlled studies of the combination of acetaminophen, aspirin, and caffeine. Author(s): Goldstein J, Hoffman HD, Armellino JJ, Battikha JP, Hamelsky SW, Couch J, Blumenthal H, Lipton RB. Source: Cephalalgia : an International Journal of Headache. 1999 September; 19(7): 68491. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10524663&dopt=Abstract
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Treatment strategies for early presenting acetaminophen overdose: a survey of medical directors of poison centers in North America and Europe. Author(s): Kozer E, McGuigan M. Source: Human & Experimental Toxicology. 2002 March; 21(3): 123-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102537&dopt=Abstract
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Unintentional acetaminophen ingestion in children and the potential for hepatotoxicity. Author(s): Caravati EM. Source: Journal of Toxicology. Clinical Toxicology. 2000; 38(3): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866329&dopt=Abstract
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Unusual presentation of acetaminophen toxicity. Author(s): Waseem M, Bomann S, Gernsheimer J, Pinkert H. Source: The American Journal of Emergency Medicine. 2003 January; 21(1): 88-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563593&dopt=Abstract
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Update: the clinical importance of acetaminophen hepatotoxicity in non-alcoholic and alcoholic subjects. Author(s): Tanaka E, Yamazaki K, Misawa S. Source: Journal of Clinical Pharmacy and Therapeutics. 2000 October; 25(5): 325-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11123483&dopt=Abstract
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Use of acetaminophen in alcoholic patients: comment on the 2000 update of the American College of Rheumatology recommendations for management of hip and knee osteoarthritis. Author(s): Dart RC, Kuffner EK. Source: Arthritis and Rheumatism. 2001 October; 44(10): 2449; Author Reply 2455-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11665990&dopt=Abstract
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Use of acetaminophen in the treatment of osteoarthritis in patients with liver disease: comment on the 2000 update of the American College of Rheumatology recommendations for management of hip and knee osteoarthritis. Author(s): Lynch JM, Fox TM. Source: Arthritis and Rheumatism. 2001 October; 44(10): 2448-9; Author Reply 2455-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11665988&dopt=Abstract
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Use of NSAIDs, COX-2 inhibitors, and acetaminophen and associated coprescriptions of gastroprotective agents in an elderly population. Author(s): Rahme E, Marentette MA, Kong SX, Lelorier J. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 595-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522832&dopt=Abstract
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Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. Author(s): Gunnell D, Murray V, Hawton K. Source: Suicide & Life-Threatening Behavior. 2000 Winter; 30(4): 313-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210057&dopt=Abstract
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Use of salivary acetaminophen concentration to assess gastric emptying rate of liquids. Author(s): Sanaka M, Kuyama Y, Nishinakagawa S, Mineshita S. Source: Journal of Gastroenterology. 2000; 35(6): 429-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10864349&dopt=Abstract
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Utility of acetaminophen screening in unsuspected suicidal ingestions. Author(s): Lucanie R, Chiang WK, Reilly R. Source: Vet Hum Toxicol. 2002 June; 44(3): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046974&dopt=Abstract
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Warfarin and acetaminophen interaction. Author(s): Gebauer MG, Nyfort-Hansen K, Henschke PJ, Gallus AS. Source: Pharmacotherapy. 2003 January; 23(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523469&dopt=Abstract
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Warfarin-acetaminophen drug interaction revisited. Author(s): Shek KL, Chan LN, Nutescu E. Source: Pharmacotherapy. 1999 October; 19(10): 1153-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512064&dopt=Abstract
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Warning note on a blood gas report leading to diagnosis of acetaminophen overdose. Author(s): Ashtekar CS, Vyas H. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 July; 4(3): 370-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831423&dopt=Abstract
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What is the rate of adverse events after oral N-acetylcysteine administered by the intravenous route to patients with suspected acetaminophen poisoning? Author(s): Kao LW, Kirk MA, Furbee RB, Mehta NH, Skinner JR, Brizendine EJ. Source: Annals of Emergency Medicine. 2003 December; 42(6): 741-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634597&dopt=Abstract
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What now about acetaminophen? Author(s): Zwahlen M, Juni P, Egger M. Source: Archives of Internal Medicine. 2003 August 11-25; 163(15): 1862-3; Author Reply 1863. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912727&dopt=Abstract
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When acetaminophen use becomes toxic. Treating acute accidental and intentional overdose. Author(s): Salgia AD, Kosnik SD. Source: Postgraduate Medicine. 1999 April; 105(4): 81-4, 87, 90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10223088&dopt=Abstract
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CHAPTER 2. NUTRITION AND ACETAMINOPHEN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and acetaminophen.
Finding Nutrition Studies on Acetaminophen 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 “acetaminophen” (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 information is typical of that found when using the “Full IBIDS Database” to search for “acetaminophen” (or a synonym): •
A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury. Author(s): Division of Environmental Sciences, Forensic and Social Environmental Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan. Source: Ishida, Yuko Kondo, Toshikazu Ohshima, Tohru Fujiwara, Hiromi Iwakura, Yoichiro Mukaida, Naofumi FASEB-J. 2002 August; 16(10): 1227-36 1530-6860
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Acetaminophen hepatotoxicity and mechanisms of its protection by N-acetylcysteine: a study of Hep3B cells. Author(s): Pediatric Research and Electron Microscopy Unit, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Source: MaNovember, Irena Hirsh, Mark Iancu, Theodore C Exp-Toxicol-Pathol. 2002 February; 53(6): 489-500 0940-2993
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Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro. Author(s): Department of Histology and Embryology, Istanbul Medical School, Faculty of Science, Turkey.
[email protected] Source: Bilir, A Altinoz, M A Attar, E Erkan, M Aydiner, A Neoplasma. 2002; 49(1): 3842 0028-2685
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Acetaminophen poisoning: an update for the intensivist. Author(s): Specialist Registrar in Medicine and Clinical Toxicology, National Poisons Information Service, Guy's & St Thomas' NHS Trust, London, UK.
[email protected] Source: Dargan, Paul I Jones, Alison L Crit-Care. 2002 April; 6(2): 108-10 1364-8535
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Acetaminophen toxicity: suicidal vs. accidental. Author(s): Department of Internal Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
[email protected] Source: Gyamlani, Geeta G Parikh, Chirag R Crit-Care. 2002 April; 6(2): 155-9 1364-8535
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Acute acetaminophen overdose in adolescents and adults. Author(s): Duke University Medical Center, Durham, NC, USA. Source: Hamm, J Crit-Care-Nurse. 2000 June; 20(3): 69-74 0279-5442
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Antioxidant properties of acetaminophen and cardioprotection. Author(s): Department of Cell Biology and Neurosciences, Rutgers University, Piscataway, NJ 08854-8082, USA.
[email protected] Source: Merrill, G F Goldberg, E Basic-Res-Cardiol. 2001 September; 96(5): 423-30 03008428
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Combination acetaminophen and doxapram potentiated hepatotoxicity in mouse primary cultured hepatocytes. Author(s): Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical University, Sendai, Japan.
[email protected] Source: Kanno, S Ishikawa, M Takayanagi, M Takayanagi, Y Sasaki, K Methods-FindExp-Clin-Pharmacol. 1999 December; 21(10): 647-52 0379-0355
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Dissolution difference between acidic and neutral media of acetaminophen tablets containing a super disintegrant and a soluble excipient. II. Author(s): Chia Nan College of Pharmacy and Science, Jen-Te Hsiang, Tainan Hsien, Taiwan.
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Source: Chen, C R Cho, S L Lin, C K Lin, Y H Chiang, S T Wu, H L Chem-Pharm-Bull(Tokyo). 1998 March; 46(3): 478-81 0009-2363 •
Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol. Source:
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Effect of inhibitors of nitric oxide synthase on acetaminophen-induced hepatotoxicity in mice. Author(s): Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
[email protected] Source: Hinson, Jack A Bucci, Thomas J Irwin, Lisa K Michael, Sherryll L Mayeux, Philip R Nitric-Oxide. 2002 March; 6(2): 160-7 1089-8603
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Effect of long-term multiple nifedipine administration on the antinociceptive activity of acetaminophen. Author(s): Laboratory of Drug Toxicology, Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
[email protected] Source: Koleva, M Dimova, S Methods-Find-Exp-Clin-Pharmacol. 2001 December; 23(10): 537-40 0379-0355
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Effect of riboflavin status on acetaminophen toxicity in the rat [Vitamin B2]. Source: Raheja, K. Turkki, P.R. Linscheer, W.G. Cho, C. Drug-Nutr-Interact. New York : Alan R. Liss. 1983. volume 2 (3) page 183-191. ill. 0272-3530
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Effects of dietary methionine and ethanol on acetaminophen hepatotoxicity in mice. Source: Reicks, M M Hathcock, J N Drug-Nutr-Interact. 1984; 3(1): 43-51 0272-3530
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Effects of molybdate and pentachlorophenol on the sulfation of acetaminophen. Author(s): Center for Environmental and Occupational Health, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160-7417, USA. Source: Boles, J W Klaassen, C D Toxicology. 2000 April 20; 146(1): 23-35 0300-483X
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Glucuronidation of acetaminophen catalyzed by multiple rat phenol UDPglucuronosyltransferases. Author(s): Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA. Source: Kessler, Fay K Kessler, Marissa R Auyeung, Diana J Ritter, Joseph K DrugMetab-Dispos. 2002 Mar; 30(3): 324-30 0090-9556
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Granulation of acetaminophen by a rotating fluidized-bed granulator. Author(s): Faculty of Pharmacy, Meijo University, Nagoya, Japan. Source: Kawaguchi, T Sunada, H Yonezawa, Y Danjo, K Hasegawa, M Makino, T Sakamoto, H Fujita, K Tanino, T Kokubo, H Pharm-Dev-Technol. 2000; 5(2): 141-51 10837450
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Immunochemical comparison of 3'-hydroxyacetanilide and acetaminophen binding in mouse liver. Author(s): Department of Pharmacology & Therapeutics, J. Hillis Miller Health Science Center, University of Florida, Gainesville, FL 32611, USA. Source: Salminen, W F Roberts, S M Pumford, N R Hinson, J A Drug-Metab-Dispos. 1998 March; 26(3): 267-71 0090-9556
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Interventions for paracetamol (acetaminophen) overdoses. Author(s): Centre for Clinical Intervention Research, Copenhagen University Hospital, Department 71-02, H:S Rigshospitalet, Copenhagen O, Denmark, DK 2100.
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Source: Brok, J Buckley, N Gluud, C Cochrane-Database-Syst-Revolume 2002; (3): CD003328 1469-493X •
Is chronic poisoning with acetaminophen in children a frequent occurrence in Toronto? Author(s): Department of Pediatrics, Hopital Sainte-Justine, 3175 Cote-Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.
[email protected] Source: Bailey, B Lalkin, A Kapur, B M Koren, G Can-J-Clin-Pharmacol. 2001 Summer; 8(2): 96-101 1198-581X
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Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Author(s): Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA.
[email protected] Source: Court, M H Greenblatt, D J Pharmacogenetics. 2000 June; 10(4): 355-69 0960-314X
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Paracetamol (acetaminophen) poisoning. Author(s): Canberra Hospital, Canberra, Australia. Source: Buckley, N Eddleston, M Clin-Evid. 2002 June; (7): 1263-9 1462-3846
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Peroxynitrite is a critical mediator of acetaminophen hepatotoxicity in murine livers: protection by glutathione. Author(s): Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA. Source: Knight, T R Ho, Y S Farhood, A Jaeschke, H J-Pharmacol-Exp-Ther. 2002 November; 303(2): 468-75 0022-3565
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Protective effect of acetaminophen against colon cancer initiation effects of 3,2'dimethyl-4-aminobiphenyl in rats. Author(s): Department of Pathology, New York Medical University, Valhalla, NY 10595, USA.
[email protected] Source: Williams, G M Iatropoulos, M J Jeffrey, A M Shirai, T Eur-J-Cancer-Prevolume 2002 February; 11(1): 39-48 0959-8278
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S-adenosyl-L-methionine (SAMe) for the treatment of acetaminophen toxicity in a dog. Author(s): Department of Clinical Sciences, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853-6401, USA. Source: Wallace, Kevin P Center, Sharon A Hickford, Fiona H Warner, Karen L Smith, Scott J-Am-Anim-Hosp-Assoc. 2002 May-June; 38(3): 246-54 0587-2871
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Simultaneous determination of acetaminophen, acetylsalicylic acid and ascorbic acid in tablet form using HPLC. Author(s): Military Drug Factory, Gazi University, Ankara, Turkey. Source: Akay, C Gumusel, B Degim, T Tartilmis, S Cevheroglu, S Drug-Metabol-DrugInteract. 1999; 15(2-3): 197-205 0792-5077
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Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose. Author(s): Medical Department A, Division of Hepatology A-2121, Rigshospitalet, Copenhagen, Denmark.
[email protected] Source: Schiodt, F V Ott, P Tygstrup, N Dahl, B Bondesen, S Liver-Transpl. 2001 August; 7(8): 732-8 1527-6465
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Troglitazone enhances the hepatotoxicity of acetaminophen by inducing CYP3A in rats. Author(s): Department of Environmental Health, Medical University of Yamanashi, Yamanashi Tamaho 409-3898, Japan. Source: Li, Jue Kaneko, Takashi Wang, Yuan Qin, Li Qiang Wang, Pei Yu Sato, Akio Toxicology. 2002 July 1; 176(1-2): 91-100 0300-483X
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Two new spectrophotometric approaches to the multicomponent analysis of the acetaminophen and caffeine in tablets by classical least-squares and principal component regression techniques. Author(s): Department of Analytical Chemistry, Faculty of Pharmacy, University of Ankara, Tandogan Ankara, Turkey.
[email protected] Source: Dinc, E Baleanu, D Farmaco. 2002 January; 57(1): 33-7 0014-827X
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Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men. Author(s): Department of Nutrition, Harvard School of Public Health, Boston, Mass, USA.
[email protected] Source: Aldoori, W H Giovannucci, E L Rimm, E B Wing, A L Willett, W C Arch-FamMed. 1998 May-June; 7(3): 255-60 1063-3987
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/
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to acetaminophen; 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 Ascorbic Acid Alternative names: Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C (Ascorbic Acid) Alternative names: Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Folate Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com
Nutrition
Glucosamine/Chondroitin Source: Healthnotes, Inc.; www.healthnotes.com •
Food and Diet Gluten-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Pain Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ACETAMINOPHEN
ALTERNATIVE
MEDICINE
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Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to acetaminophen. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to acetaminophen 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 “acetaminophen” (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 acetaminophen: •
A novel proanthocyanidin IH636 grape seed extract increases in vivo Bcl-XL expression and prevents acetaminophen-induced programmed and unprogrammed cell death in mouse liver. Author(s): Ray SD, Kumar MA, Bagchi D. Source: Archives of Biochemistry and Biophysics. 1999 September 1; 369(1): 42-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10462439&dopt=Abstract
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Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2. Author(s): Raucy JL, Lasker JM, Lieber CS, Black M. Source: Archives of Biochemistry and Biophysics. 1989 June; 271(2): 270-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2729995&dopt=Abstract
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Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: its probable antioxidant effect is potentiated by the flavonoid silybin. Author(s): Garrido A, Arancibia C, Campos R, Valenzuela A. Source: Pharmacology & Toxicology. 1991 July; 69(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1682911&dopt=Abstract
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Acetaminophen hepatotoxicity in rats is attenuated by silybin dihemisuccinate. Author(s): Campos R, Garrido A, Guerra R, Valenzuela A. Source: Prog Clin Biol Res. 1988; 280: 375-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3174702&dopt=Abstract
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Acetaminophen hepatotoxicity: influence of phenobarbital and beta-naphthoflavone treatment in obese and lean Zucker rats. Author(s): Tuntaterdtum S, Chaudhary IP, Cibull M, Robertson LW, Blouin RA. Source: Toxicology and Applied Pharmacology. 1993 December; 123(2): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8248929&dopt=Abstract
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Acetaminophen induced pancreatitis. Author(s): Mofenson HC, Caraccio TR, Nawaz H, Steckler G. Source: Journal of Toxicology. Clinical Toxicology. 1991; 29(2): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1675695&dopt=Abstract
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Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro. Author(s): Bilir A, Altinoz MA, Attar E, Erkan M, Aydiner A. Source: Neoplasma. 2002; 49(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044058&dopt=Abstract
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Acetaminophen toxicity in cultured trout liver cells. II. Maintenance of cytochrome P450 1A1. Author(s): Miller MR, Saito N, Blair JB, Hinton DE. Source: Experimental and Molecular Pathology. 1993 April; 58(2): 127-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8495716&dopt=Abstract
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Acetaminophen-induced toxicity to human epidermoid cell line A431 and hepatoblastoma cell line Hep G2, in vitro, is diminished by silymarin. Author(s): Shear NH, Malkiewicz IM, Klein D, Koren G, Randor S, Neuman MG. Source: Skin Pharmacol. 1995; 8(6): 279-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8688194&dopt=Abstract
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Activation of acetaminophen oxidation in rat liver microsomes by caffeine. Author(s): Nouchi T, Lasker JM, Lieber CS.
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Source: Toxicology Letters. 1986 July-August; 32(1-2): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3738921&dopt=Abstract •
Ameliorative effect of an urinary preparation on acetaminophen and D-galactosamine induced hepatotoxicity in rats. Author(s): Lai TY, Wu YW, Lin WC. Source: The American Journal of Chinese Medicine. 1999; 27(1): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10354819&dopt=Abstract
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Ameliorative effect of Silene aprica on liver injuries induced by carbon tetrachloride and acetaminophen. Author(s): Ko YJ, Hsieh WT, Wu YW, Lin WC. Source: The American Journal of Chinese Medicine. 2002; 30(2-3): 235-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230012&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351354&dopt=Abstract
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Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity. Author(s): Lewerenz V, Hanelt S, Nastevska C, El-Bahay C, Rohrdanz E, Kahl R. Source: Toxicology. 2003 September 30; 191(2-3): 179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965121&dopt=Abstract
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Ascorbic acid protects against acetaminophen- and cocaine-induced hepatic damage in mice. Author(s): Peterson FJ, Knodell RG. Source: Drug Nutr Interact. 1984; 3(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6510239&dopt=Abstract
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Assessment and treatment of acetaminophen overdose. Author(s): Lewis RK, Paloucek FP. Source: Clin Pharm. 1991 October; 10(10): 765-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1683827&dopt=Abstract
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Brief safety updates: acetaminophen, ASA and kava. Author(s): Wooltorton E.
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Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 October 29; 167(9): 1034. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403745&dopt=Abstract •
Central analgesic effect of acetaminophen but not of aspirin. Author(s): Piletta P, Porchet HC, Dayer P. Source: Clinical Pharmacology and Therapeutics. 1991 April; 49(4): 350-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2015724&dopt=Abstract
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Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics. Author(s): Patten CJ, Thomas PE, Guy RL, Lee M, Gonzalez FJ, Guengerich FP, Yang CS. Source: Chemical Research in Toxicology. 1993 July-August; 6(4): 511-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8374050&dopt=Abstract
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Effect of a bioflavonoid dietary supplement on acetaminophen-induced oxidative injury to feline erythrocytes. Author(s): Allison RW, Lassen ED, Burkhard MJ, Lappin MR. Source: J Am Vet Med Assoc. 2000 October 15; 217(8): 1157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043685&dopt=Abstract
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Effect of Taxol on cytochrome P450 3A and acetaminophen toxicity in cultured rat hepatocytes: comparison to dexamethasone. Author(s): Kostrubsky VE, Lewis LD, Wood SG, Sinclair PR, Wrighton SA, Sinclair JF. Source: Toxicology and Applied Pharmacology. 1997 January; 142(1): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9007036&dopt=Abstract
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Effects of “Chinese yam” on hepato-nephrotoxicity of acetaminophen in rats. Author(s): Lee SC, Tsai CC, Chen JC, Lin JG, Lin CC, Hu ML, Lu S. Source: Acta Pharmacologica Sinica. 2002 June; 23(6): 503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060523&dopt=Abstract
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Effects of Corylus avellana in acetaminophen and CCl4 induced toxicosis. Author(s): Rusu MA, Bucur N, Puica C, Tamas M. Source: Phytotherapy Research : Ptr. 1999 March; 13(2): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10190184&dopt=Abstract
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Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Author(s): Li Y, Wang E, Patten CJ, Chen L, Yang CS.
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Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1994 JulyAugust; 22(4): 566-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7956731&dopt=Abstract •
Efficacy of charcoal cathartic versus ipecac in reducing serum acetaminophen in a simulated overdose. Author(s): McNamara RM, Aaron CK, Gemborys M, Davidheiser S. Source: Annals of Emergency Medicine. 1989 September; 18(9): 934-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2569851&dopt=Abstract
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Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group. Author(s): Friedman AD, Barton LL. Source: Pediatric Emergency Care. 1990 March; 6(1): 6-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2320489&dopt=Abstract
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Efficacy of sponging vs. acetaminophen for reduction of fever. Author(s): Schaffer SJ. Source: Pediatric Emergency Care. 1990 September; 6(3): 255. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2278583&dopt=Abstract
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Efficacy of sponging vs. acetaminophen for reduction of fever. Author(s): Barton LL, Friedman AD. Source: Pediatric Emergency Care. 1990 June; 6(2): 171. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2371159&dopt=Abstract
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Evaluation of acetaminophen-induced developmental toxicity using FETAX. Author(s): Fort DJ, Rayburn JR, Bantle JA. Source: Drug and Chemical Toxicology. 1992; 15(4): 329-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1459044&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297846&dopt=Abstract
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Evaluation of the protective potential of Artemisia acetaminophen- and CCl4-induced liver damage. Author(s): Janbaz KH, Gilani AH.
maritima
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Source: Journal of Ethnopharmacology. 1995 June 23; 47(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7564420&dopt=Abstract •
Heart donation after fatal acetaminophen poisoning. Author(s): Hantson P, Vekemans MC, Laterre PF, Vanormelingen P, Mahieu P, Koerner MM. Source: Journal of Toxicology. Clinical Toxicology. 1997; 35(3): 325-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9140331&dopt=Abstract
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Hepatoprotective ability of a novel botanical formulation on mild liver injury in rats produced by acute acetaminophen and/or alcohol ingestion. Author(s): Echard BW, Talpur NA, Fan AY, Bagchi D, Preuss HG. Source: Res Commun Mol Pathol Pharmacol. 2001 July-August; 110(1-2): 73-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090358&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999435&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675154&dopt=Abstract
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Histocytological study on the possible mechanism of acetaminophen cataractogenesis in mouse eye. Author(s): Zhao C, Shichi H. Source: Experimental and Molecular Pathology. 1995 October; 63(2): 118-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8941046&dopt=Abstract
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Hmong folk remedies: limited acetylation of opium by aspirin and acetaminophen. Author(s): Smith RM, Nelsen LA. Source: J Forensic Sci. 1991 January; 36(1): 280-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1826129&dopt=Abstract
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Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population. Author(s): Bond GR, Requa RK, Krenzelok EP, Normann SA, Tendler JD, Morris CL, McCoy DJ, Thompson MW, McCarthy T, Roblez J, et al.
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Source: Annals of Emergency Medicine. 1993 September; 22(9): 1403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8103306&dopt=Abstract •
Inhibition of acetaminophen glucuronidation by oxazepam. Author(s): Dybing E. Source: Biochemical Pharmacology. 1976 June 15; 25(12): 1421-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=938564&dopt=Abstract
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Inhibitory effects of acetaminophen, 7,8-benzoflavone and methimazole towards Nnitrosodimethylamine mutagenesis in Arabidopsis thaliana. Author(s): Gichner T, Veleminsky J, Wagner ED, Plewa MJ. Source: Mutation Research. 1993 June; 300(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7683770&dopt=Abstract
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Interaction of caffeine with acetaminophen. 1. Correlation of the effect of caffeine on acetaminophen hepatotoxicity and acetaminophen bioactivation following treatment of mice with various cytochrome P450 inducing agents. Author(s): Jaw S, Jeffery EH. Source: Biochemical Pharmacology. 1993 August 3; 46(3): 493-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8347173&dopt=Abstract
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Loss of CYP2E1 and CYP1A2 activity as a function of acetaminophen dose: relation to toxicity. Author(s): Snawder JE, Roe AL, Benson RW, Roberts DW. Source: Biochemical and Biophysical Research Communications. 1994 August 30; 203(1): 532-9. Erratum In: Biochem Biophys Res Commun 1995 January 5; 206(1): 437. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8074700&dopt=Abstract
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Mechanisms of protection by S-allylmercaptocysteine against acetaminopheninduced liver injury in mice. Author(s): Sumioka I, Matsura T, Kasuga S, Itakura Y, Yamada K. Source: Japanese Journal of Pharmacology. 1998 October; 78(2): 199-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829623&dopt=Abstract
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Model systems for metabolism studies. Biomimetic oxidation of acetaminophen and ellipticine derivatives with water-soluble metalloporphyrins associated to potassium monopersulfate. Author(s): Bernadou J, Bonnafous M, Labat G, Loiseau P, Meunier B. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1991 MarchApril; 19(2): 360-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1676637&dopt=Abstract
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Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen intoxication. Author(s): Tobias JD, Gregory DF, Deshpande JK. Source: Pediatric Emergency Care. 1992 December; 8(6): 345-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1360651&dopt=Abstract
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Pharmacokinetic study on acetaminophen: interaction with a Chinese medicine. Author(s): Qi J, Toyoshima A, Honda Y, Mineshita S. Source: J Med Dent Sci. 1997 March; 44(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9385040&dopt=Abstract
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Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and N-acetylcysteine. Author(s): Zhao C, Shichi H. Source: Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. 1998 August; 14(4): 345-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9715438&dopt=Abstract
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Prevention of acetaminophen-induced liver damage by Berberis aristata leaves. Author(s): Gilani AH, Janbaz KH. Source: Biochemical Society Transactions. 1992 November; 20(4): 347S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1487011&dopt=Abstract
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Preventive and curative effects of Artemisia absinthium on acetaminophen and CCl4induced hepatotoxicity. Author(s): Gilani AH, Janbaz KH. Source: General Pharmacology. 1995 March; 26(2): 309-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7590079&dopt=Abstract
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Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats. Author(s): Yamada S, Murawaki Y, Kawasaki H. Source: Biochemical Pharmacology. 1993 September 14; 46(6): 1081-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8216352&dopt=Abstract
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Protective effect of ajoene on acetaminophen-induced hepatic injury in mice. Author(s): Hattori A, Yamada N, Nishikawa T, Fukuda H, Fujino T. Source: Bioscience, Biotechnology, and Biochemistry. 2001 November; 65(11): 2555-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791733&dopt=Abstract
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Protective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice. Author(s): Lin MC, Wang EJ, Patten C, Lee MJ, Xiao F, Reuhl KR, Yang CS.
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Source: Journal of Biochemical Toxicology. 1996; 11(1): 11-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8806047&dopt=Abstract •
Protective effect of moutan cortex extract on acetaminophen-induced cytotoxicity in human Chang liver cells. Author(s): Shon YH, Nam KS. Source: Biological & Pharmaceutical Bulletin. 2002 November; 25(11): 1427-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419953&dopt=Abstract
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Protective effects of diallyl sulfide on acetaminophen-induced toxicities. Author(s): Hu JJ, Yoo JS, Lin M, Wang EJ, Yang CS. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1996 October; 34(10): 963-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9012771&dopt=Abstract
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Protective effects of garlic and related organosulfur compounds on acetaminopheninduced hepatotoxicity in mice. Author(s): Wang EJ, Li Y, Lin M, Chen L, Stein AP, Reuhl KR, Yang CS. Source: Toxicology and Applied Pharmacology. 1996 January; 136(1): 146-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8560468&dopt=Abstract
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Reduction in caffeine toxicity by acetaminophen. Author(s): Deng JF, Spyker DA, Rall TW, Steward O. Source: Journal of Toxicology. Clinical Toxicology. 1982 December; 19(10): 1031-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6308277&dopt=Abstract
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Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Author(s): Campos R, Garrido A, Guerra R, Valenzuela A. Source: Planta Medica. 1989 October; 55(5): 417-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2813577&dopt=Abstract
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Studies on protective effect of Cyperus scariosus extract on acetaminophen and CCl4induced hepatotoxicity. Author(s): Gilani AU, Janbaz KH. Source: General Pharmacology. 1995 May; 26(3): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7789738&dopt=Abstract
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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.
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Source: Arch Pharm Res. 1998 October; 21(5): 508-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9875486&dopt=Abstract •
Subtleties of managing acetaminophen poisoning. Author(s): Rose SR. Source: Am J Hosp Pharm. 1994 December 15; 51(24): 3065-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7856628&dopt=Abstract
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Sulfation of acetaminophen by the perfused rat liver: the effect of red blood cell carriage. Author(s): Pang KS, Barker F, Simard A, Schwab AJ, Goresky CA. Source: Hepatology (Baltimore, Md.). 1995 July; 22(1): 267-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7601421&dopt=Abstract
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Superoxide dismutase and catalase protect cultured hepatocytes from the cytotoxicity of acetaminophen. Author(s): Kyle ME, Miccadei S, Nakae D, Farber JL. Source: Biochemical and Biophysical Research Communications. 1987 December 31; 149(3): 889-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3122747&dopt=Abstract
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The effect of garlic extract on human metabolism of acetaminophen. Author(s): Gwilt PR, Lear CL, Tempero MA, Birt DD, Grandjean AC, Ruddon RW, Nagel DL. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1994 March; 3(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8049637&dopt=Abstract
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The hepatoprotective effects of Solanum alatum Moench. on acetaminophen-induced hepatotoxicity in mice. Author(s): Lin SC, Chung TC, Ueng TH, Lin YH, Hsu SH, Chiang CL, Lin CC. Source: The American Journal of Chinese Medicine. 2000; 28(1): 105-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10794122&dopt=Abstract
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The killing of cultured hepatocytes by N-acetyl-p-benzoquinone imine (NAPQI) as a model of the cytotoxicity of acetaminophen. Author(s): Harman AW, Kyle ME, Serroni A, Farber JL. Source: Biochemical Pharmacology. 1991 April 15; 41(8): 1111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2009090&dopt=Abstract
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The PPAR activator docosahexaenoic acid prevents acetaminophen hepatotoxicity in male CD-1 mice.
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Author(s): Nguyen KA, Carbone JM, Silva VM, Chen C, Hennig GE, Whiteley HE, Manautou JE. Source: Journal of Toxicology and Environmental Health. Part A. 1999 October 15; 58(3): 171-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10522648&dopt=Abstract •
The protective effect of garlic oil on hepatotoxicity induced by acetaminophen in mice and comparison with N-acetylcysteine. Author(s): Kalantari H, Salehi M. Source: Saudi Med J. 2001 December; 22(12): 1080-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802181&dopt=Abstract
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Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice. Author(s): Sumioka I, Matsura T, Yamada K. Source: European Journal of Pharmacology. 2001 December 21; 433(2-3): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755151&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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The following is a specific Web list relating to acetaminophen; 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 Acetaminophen Poisoning Source: Integrative Medicine Communications; www.drkoop.com Burns Source: Integrative Medicine Communications; www.drkoop.com Bursitis Source: Integrative Medicine Communications; www.drkoop.com Chickenpox and Shingles Source: Integrative Medicine Communications; www.drkoop.com Chronic Fatigue Syndrome Source: Integrative Medicine Communications; www.drkoop.com Cold Sores Source: Healthnotes, Inc.; www.healthnotes.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Ear Infection Source: Integrative Medicine Communications; www.drkoop.com Epstein-Barr Virus Source: Integrative Medicine Communications; www.drkoop.com Fever of Unknown Origin Source: Integrative Medicine Communications; www.drkoop.com Fibrocystic Breast Disease Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Flu Source: Integrative Medicine Communications; www.drkoop.com Genital Herpes Source: Healthnotes, Inc.; www.healthnotes.com
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Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Herpes Zoster and Varicella Viruses Source: Integrative Medicine Communications; www.drkoop.com Influenza Source: Integrative Medicine Communications; www.drkoop.com Insect Bites and Stings Source: Integrative Medicine Communications; www.drkoop.com Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Low Back Pain Source: Healthnotes, Inc.; www.healthnotes.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Measles Source: Integrative Medicine Communications; www.drkoop.com Mononucleosis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Otitis Media Source: Integrative Medicine Communications; www.drkoop.com Roseola Source: Integrative Medicine Communications; www.drkoop.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Shingles and Chickenpox Source: Integrative Medicine Communications; www.drkoop.com Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com
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Sprains and Strains Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Healthnotes, Inc.; www.healthnotes.com Varicella and Herpes Zoster Viruses Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Testing for Stomach Acidity Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements 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, 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 Alka-Seltzer Plus Source: Healthnotes, Inc.; www.healthnotes.com Andrographis Source: Prima Communications, Inc.www.personalhealthzone.com Aspirin/Acetaminophen Alternative names: Buffets Vanquish, Extra Strength Excedrin, Gelpirin, Goody's, Maximum Pain Relief Pamprin, Menoplex, Supac Source: Prima Communications, Inc.www.personalhealthzone.com Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Chlorpheniramine Source: Healthnotes, Inc.; www.healthnotes.com
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Codeine Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cysteine Source: Integrative Medicine Communications; www.drkoop.com Darvocet N Source: Healthnotes, Inc.; www.healthnotes.com Dextromethorphan Source: Healthnotes, Inc.; www.healthnotes.com Diphenhydramine Source: Healthnotes, Inc.; www.healthnotes.com Endocet Source: Healthnotes, Inc.; www.healthnotes.com Ephedrine and Pseudoephedrine Source: Healthnotes, Inc.; www.healthnotes.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Excedrin Pm Source: Healthnotes, Inc.; www.healthnotes.com Fioricet Source: Healthnotes, Inc.; www.healthnotes.com Glucosamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,790,00.html Glutathione Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,854,00.html Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lortab Source: Healthnotes, Inc.; www.healthnotes.com
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Mentha Alternative names: Pennyroyal; Mentha/Hedeoma pulegium Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Mentha X Piperita Source: Integrative Medicine Communications; www.drkoop.com Methionine Source: Prima Communications, Inc.www.personalhealthzone.com Metoclopramide Source: Healthnotes, Inc.; www.healthnotes.com Midrin Source: Healthnotes, Inc.; www.healthnotes.com 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 NAC (N-Acetylcysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html N-Acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com N-Acetyl Cysteine (NAC) Source: Prima Communications, Inc.www.personalhealthzone.com Nyquil Source: Healthnotes, Inc.; www.healthnotes.com Nyquil Hot Therapy Powder Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Peppermint Alternative names: Mentha x piperita Source: Integrative Medicine Communications; www.drkoop.com Percocet Source: Healthnotes, Inc.; www.healthnotes.com
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Phrenilin Source: Healthnotes, Inc.; www.healthnotes.com Propacet 100 Source: Healthnotes, Inc.; www.healthnotes.com Roxicet Source: Healthnotes, Inc.; www.healthnotes.com S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe Source: Integrative Medicine Communications; www.drkoop.com Silybum Marianum Source: Integrative Medicine Communications; www.drkoop.com St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Theraflu Source: Healthnotes, Inc.; www.healthnotes.com Tylenol Allergy Sinus Source: Healthnotes, Inc.; www.healthnotes.com Tylenol Cold Source: Healthnotes, Inc.; www.healthnotes.com Tylenol Flu Nighttime Maximum Strength Powder Source: Healthnotes, Inc.; www.healthnotes.com Tylenol Multi-Symptom Hot Medication Source: Healthnotes, Inc.; www.healthnotes.com Tylenol PM Source: Healthnotes, Inc.; www.healthnotes.com Tylenol Sinus Source: Healthnotes, Inc.; www.healthnotes.com Tylenol with Codeine Source: Healthnotes, Inc.; www.healthnotes.com Vicodin Source: Healthnotes, Inc.; www.healthnotes.com Wygesic Source: Healthnotes, Inc.; www.healthnotes.com
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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON ACETAMINOPHEN Overview In this chapter, we will give you a bibliography on recent dissertations relating to acetaminophen. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “acetaminophen” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on acetaminophen, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Acetaminophen ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to acetaminophen. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
1. A Novel Self-sealing Chewable Sustained Release Tablet of Acetaminophen, 2. Development and Evaluation of Novel Itraconazole Oral Formulations, 3. A Novel Zero Order Release Matrix Tablet by Rakkanka, Vipaporn, PhD from Oregon State University, 2003, 330 pages http://wwwlib.umi.com/dissertations/fullcit/3098441
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Acetaminophen Toxicity and Its Prevention Studies in Isolated Mouse Hepatocytes and in the Whole Mouse by Massey, Thomas Evans; PhD from Queen's University at Kingston (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK61664
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Acetaminophen-induced Hepatotoxicity, Hepatic Congestion and Hypothermia in Mice by Walker, Robin M; PhD from Queen's University at Kingston (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK61558
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Influence of Crystallization in the Presence of [Rho]-Acetoxyacetanilide on the Physical Properties and Aqueous Dissolution Rate of Acetaminophen by Chow, Albert Hee-Lum; PhD from University of Toronto (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39157
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Role of Antioxidants and Tumor Necrosis Factor (TNF)-Alpha in Acetaminopheninduced Hepatotoxicity by Chiu, Hawjyh, PhD from Rutgers the State U. of N.J. - New Brunswick and U.M.D.N.J., 2003, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3093014
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UDP-Glucuronyl Transferase Deficiency As a Biochemical Determinant of Acetaminophen Metabolism and Toxicity by De Morais, Sonia Maria Freitas; PhD from University of Toronto (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL57032
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND ACETAMINOPHEN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning acetaminophen.
Recent Trials on Acetaminophen The following is a list of recent trials dedicated to acetaminophen.8 Further information on a trial is available at the Web site indicated. •
Randomized Study of Acetylcysteine in Patients with Acute Liver Failure Not Caused by Acetaminophen Condition(s): Acute Liver Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Texas Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of a short course (72 hours) of intravenous acetylcysteine in patients with acute liver failure for whom no antidote or specific treatment is available. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004467
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Evaluation of the Interaction Between Acetaminophen and Zidovudine Condition(s): HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID)
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These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: To determine if zidovudine (AZT) and acetaminophen (APAP) interact when given to the same patient, and if so, the manner of interaction. Patients with AIDS often require therapy with painkillers for the management of mild pain and discomfort associated with their disease, and APAP is often prescribed. AZT is being used to treat AIDS patients. It is important for doctors to understand how AZT and APAP may interact when given to the same patient, because other studies have suggested that the dosage of AZT may have to be adjusted when given with APAP in order to avoid or minimize adverse effects. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000731
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 “acetaminophen” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON ACETAMINOPHEN 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 “acetaminophen” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on acetaminophen, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Acetaminophen By performing a patent search focusing on acetaminophen, 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 acetaminophen: •
Acetamenophen composition with reduced liver toxicity Inventor(s): Ki; Min Hyo (Keonggi-do, KR), Kim; Jung Woo (Seoul, KR), Shin; Hee Jong (Kyeonggi-do, KR), Shin; Jae Soo (Seoul, KR) Assignee(s): Chong Kun Dang Corp. (kr) Patent Number: 6,048,540 Date filed: September 29, 1998 Abstract: The present invention is related to a new analgesic composition of acetaminophen targeting decreasing of liver toxicity and releasing of hangover, which comprises aspartic acid promoting alcohol metabolism and methionine alleviating liver toxicity of acetaminophen. The analgesic combination preparation according to the present invention showed same analgesic and excellent protection effect against liver toxicity compared with the single preparation of acetaminophen, and decreased the blood concentration of alcohol and acetaldehyde causing hangover through improving metabolism rates of them. The combination preparation according to the present invention, therefore, is coincident with ideal new analgesic composition of acetaminophen having a minimized side effect and a hangover releasing effect. Excerpt(s): The present invention relates to new analgesic composition comprising acetaminophen, aspartic acid and methionine, to obtain the alleviation of liver toxicity and the release of hangover as well as an analgesic effect. Acetaminophen is a typical antipyretic and analgesic agent which is used frequently instead of aspirin. However, liver toxicity of acetaminophen is recently on the rise as intensive side effect, and has been reported in many articles. The high dose administration of that induces acute liver toxicity. And especially to the patient of alcoholic liver dysfunction, a infant and indeed even a normal healthy person in the case of long-time multiple dosing, it is known that the usual dose administration of acetaminophen also induces widespread liver toxicity and can induce ophthalmic disease such as cataract. Besides, it is worried that a normal healthy person can get liver toxicity induced by acetaminophen because a modern usually takes much alcoholic drink for the release of stress coming from his place of work, etc. Acetaminophen administrated at the condition of liver function weakened by alcohol may induces severe liver toxicity with acceleration effect, and may bring about the retardation of recovery from hangover. It gets known that the liver toxicity of acetaminophen related to medicines administered together. Alcohol and medicines of barbital family, representatively, increase severely the liver toxicity of acetaminophen through the liver enzyme induction. Especially, it was reported that only usual dose administration of acetaminophen induced a pathological change of liver cell in an alcoholic poisoning person as well as high dose administration of acetaminophen after drinking of alcohol induces severe liver toxicity (J. Biol. Chem., 271(20), 12063; Biochem. Pharmacol., 50(11), 1743; Gastorenterol., 109(6), 1907; Hapatol., 22(3), 767). At low dose, only about 2% of acetaminophen is eliminated as unmetabolized form, and most of that is eliminated as inactive metabolites of sulfonated form (20.about.30%), glucuronic acid conjugation (45.about.55%), and cysteine and mercaptouric acid conjugation (15.about.55%). However, liver enzyme induction agent such as alcohol and barbital, and acetaminophen of high dose increase the activity of cytochrome P-450 in liver cell and bring about production of intensive alkylation agent, that is, active metabolite Nacetly-p-benzoquinoneimine (NAPQI) as well as main metabolite, that is, inactive
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metabolite. NAPQI produced is inactivated through the conjugation with glutathione, but if the glutathione is depleted, NAPQI binds with --SH group of cell protein and, therefore, induces liver toxicity through alkylation or oxidation. Web site: http://www.delphion.com/details?pn=US06048540__ •
Acetaminophen and dimenhydrinate analgesics Inventor(s): Hough; Douglas R. (Morrisville, PA), Nelson; Edward B. (Lower Gwynedd, PA), Raffa; Robert B. (Norristown, PA) Assignee(s): Mcneil-ppc, Inc. (skillman, Nj) Patent Number: 5,739,139 Date filed: June 20, 1996 Abstract: Disclosed are compositions comprising acetaminophen (APAP) and dimenhydrinate and methods for their use in analgesia. When acetaminophen and dimenhydrinate are within certain ratios, their pharmacological effects are superadditive. Excerpt(s): The present invention relates to analgesic compositions. More particularly, the present invention relates to analgesic compositions containing acetaminophen and dimenhydrinate. Research for improved analgesics has split into two branches. In the more traditional branch, research continues for new analgesic compounds. Recent years have seen the introduction of a number analgesic products having active ingredients not previously available. In the second branch, research has been considerably increased in the area of combination products. In combination products, improvement in analgesic effect is looked for in the interaction between two or more coadministered active ingredients. With the risk and expense associated with introducing new active compounds to the market, improved safety and efficacy in analgesic products might be better obtained by using combinations of known active compounds. Considering the advantages of working with APAP and its widely accepted use, it is of particular interest to persons investigating the advantages of combination products. It is known in the prior art to formulate so-called "nighttime analgesics", consisting of an aspirin layer and an APAP layer; the latter also containing the sleep-aid methapyrilene fumarate. A tablet of this type is described in the "Physicians Desk Reference", 28th ed., 1974, page 640 (published by Medical Economics Company, Oradell, N.J.). A. Pircio et al., Arch. Int. Pharmacodyn., 235, 116 (1978) report superadditive analgesia with a 1:125 mixture of butorphanol, an opioid analgesic, and APAP, whereas a 1:10 mixture did not show a statistically significant superadditive effect. G. Stracher et al., Int. J. Clin. Pharmacol. Biopharmacy, 17, 250 (1979) report that the combination of the non-opioid analgesics, tolmetin and APAP, allows for a marked reduction in the amount of tolmetin required to produce analgesia. U.S. Pat. No. 4,260,629 discloses that an orally administered composition of APAP and zomepirac, a non-opioid analgesic, in a particular weight ratio range produces a superadditive relief of pain in mammals. Furthermore, U.S. Pat. No. 4,132,788 discloses that 5-aroyl-1-(lower)alkylpyrrole-2-acetic acid derivatives, nonopioid analgesics, when combined with APAP or aspirin exhibit superadditive antiarthritic activity. Also, U.S. Pat. No. 5,336,691 discloses that the combination of tramadol, a centrally active analgesic, and APAP exhibits a synergistic analgesic effect when combined in certain ratios. G. B. Pat. No. 1,442,159 teaches that combinations of APAP and diphenhydramine hydrochloride in certain proportions are satisfactory in the treatment of migraine headache. U.S. Pat. Nos. 4,401,665 and 4,505,862 disclose
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combinations of aspirin, APAP and diphenhydramine dihydrogencitrate for use as an analgesic. Web site: http://www.delphion.com/details?pn=US05739139__ •
Acetaminophen sustained-release formulation Inventor(s): Ho; Chris Y. (Kalamazoo, MI), Shah; Shirish A. (Kalamazoo, MI) Assignee(s): L. Perrigo Company (allegan, Mi) Patent Number: 5,773,031 Date filed: February 27, 1996 Abstract: An orally administrable sustained-release dosage form includes particles of an active pharmaceutical ingredient which is coated with a polymeric material that is water-insoluble, but water-permeable and water-swellable, so that the sustained-release dosage form provides controlled release which is independent of certain variable physiological factors such as pH. In accordance with one aspect of the invention, the active pharmaceutical ingredient is acetaminophen and the coated acetaminophen particles are combined with uncoated acetaminophen particles to provide a combination immediate-release/sustained-release dosage form. In accordance with another aspect of the invention, the active pharmaceutical ingredient is coated with a methacrylate ester copolymer, and the coated particles are combined with uncoated particles of an active pharmaceutical ingredient to provide a combination immediaterelease/sustained-release dosage form, wherein the sustained-release component provides a release rate which is substantially independent of physiological factors such as pH. The final orally administrable dosage form can be appeared as compressed tablets, capsules or pouches. Excerpt(s): This invention relates to sustained-release pharmaceutical formulations, and more particularly to oral acetaminophen sustained-release formulations for providing extended therapeutic relief. Many medical conditions are best treated by administration of a pharmaceutical in such a way as to sustain its action over an extended period of time. For example, this kind of pharmaceutical administration can be useful for treating chronic pain, such as that associated with rheumatic or arthritic conditions. Sustainedrelease dosage forms can also be used beneficially in the administration of antiarrythmics, antihypertensives and other drugs whose sustained action is important to their efficacy. Many physiological factors influence both the gastrointestinal transit time and the release of a drug from a controlled release dosage form, and thus influence the uptake of the drug into the systemic circulation. Dosage forms should therefore be designed so that such variable factors do not compromise the efficacy and safety of the product. Ideally, such sustained-release dosage forms should release the active pharmaceutical ingredient at a controlled rate such that the amount of active pharmaceutical ingredient which is available in the body to treat the condition is maintained at a relatively constant level over an extended period of time. That is, it is desirable that active pharmaceutical ingredient be released at a reproducible, predictable rate which is substantially independent of physiological factors which can vary considerably among different individuals and even over time for a particular individual. Web site: http://www.delphion.com/details?pn=US05773031__
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Alkali metal and alkaline-earth metal salts of acetaminophen Inventor(s): Higgins, III; John D. (West Chester, PA), Martellucci; Stephen A. (Mont Clare, PA), Nadig; David (Lansdale, PA), Ohannesian; Lena A. (Blue Bell, PA), Rey; Max (Wallisellen, SE) Assignee(s): Mcneill-ppc, Inc. (fort Washington, Pa) Patent Number: 6,160,020 Date filed: June 19, 1998 Abstract: Isolated salts of acetaminophen are disclosed. Alkali metal and alkaline-earth metal salts of acetaminophen were formed by reacting the free acid of acetaminophen with the corresponding metal hydroxide and then immediately isolating the resulting salt. These salts have been found to be more water soluble and less bitter in taste than the free acid form of acetaminophen. The isolated salts may also be combined with other active ingredients. Excerpt(s): The present invention relates to salts of acetaminophen and, more particularly, to alkali metal and alkaline-earth metal salts of acetaminophen. Acetaminophen (APAP) is a well established therapeutic agent having both analgesic and antipyretic activity. Acetaminophen's relatively poor solubility in water and its bitter taste, however, make it difficult to formulate into to consumer acceptable oral dosage forms. Most commercially available acetaminophen oral dosage forms incorporate a taste masking coating on the acetaminophen particles or employ flavors and sweeteners to mask the bitter taste of the drug. Other approaches for dealing with the solubility and taste of acetaminophen include the formation of amino acid esters of acetaminophen. I. M. Kovach in Diss. Abstr. Int. B 1975, 36(2), 734-5 describes the synthesis of p-acetamidophenyl glycinate (APG),.alpha.-p-acetamidophenyl aspartate (AAPA) and.beta.-p-acetamidophenyl aspartate (BAPA). These esters are reported to have a less bitter taste than acetaminophen. APG-HBr was five times more water soluble than acetaminophen, whereas BAPA-HCl was four times less water soluble than APAP. Web site: http://www.delphion.com/details?pn=US06160020__
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Aqueous pharmaceutical suspension and process for preparation thereof Inventor(s): Ratnaraj; Sheila M. (North Wales, PA), Sunshine; Warren L. (Dresher, PA) Assignee(s): Mcneil-ppc, Inc. (skillman, Nj) Patent Number: 5,658,919 Date filed: September 9, 1996 Abstract: The present invention relates to an aqueous pharmaceutical suspension composition containing suspended acetaminophen and at least one additional pharmaceutical active, a suspension system containing xanthan gum, a mixture of microcrystalline cellulose and sodium carboxymethylcellulose and an auxiliary suspending agent selected from the group consisting of hydroxyethylcellulose and a pharmaceutically acceptable salt of carboxymethylcellulose, an effective amount of a taste-masking composition; and water, as well as a process for producing such aqueous pharmaceutical suspensions. Excerpt(s): The present invention relates to aqueous pharmaceutical suspensions and, more particularly, to aqueous suspensions containing suspended acetaminophen, at
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least one additional pharmaceutical active, a suspending system and a taste-masking composition. This invention also relates to a process for preparing such suspensions. Orally administered drugs are provided to the patient in many dosage forms, including solid forms such as capsules, caplets or tablets and liquid forms such as solutions, emulsions or suspensions. Pharmaceuticals administered in solid form are usually intended to be swallowed whole. The disagreeable taste of the drug is generally not of concern when formulating swallowable dosage forms, because the pharmaceutical's taste can be easily masked with an exterior coating. Children, older persons, and many other persons including disabled or incapacitated patients often have trouble swallowing tablets or capsules. In these situations, it is desirable to provide the drug either in a chewable solid form or a liquid form. For many patients, including pediatric and geriatric patients, a liquid oral dosage form is preferred over a chewable dosage form. A liquid dosage is especially preferred for this class of patients because of the ease with which it may be swallowed. Additionally, patients may be more inclined to comply with their medication instruction if the dosages are easier to ingest. Web site: http://www.delphion.com/details?pn=US05658919__ •
Coated active tablet(s) Inventor(s): Barkley; Aaron (Willow Grove, PA), Callahan; Timothy Patrick (Malvern, PA), Flanagan; John (Neshanic Station, NJ), Nicholson; Richard E. (Birdsboro, PA), Smith; Terry L. (Pottstown, PA) Assignee(s): Monsanto Company (st. Louis, Mo) Patent Number: 6,485,747 Date filed: October 11, 1999 Abstract: A tablet coating useful for coating an active selected from the group consisting of aspirin, ibuprofen, naproxin sodium, acetaminophen, celecoxib, sildenafil citrate, alendronate sodium, an analgesic in combination with one or more of an antitussive, antihistamine, decongestant and expectorant, oxaprozin, comprising gellan gum along with a process which comprises admixing gellan gum and water under effective shear conditions to prepare an aqueous gellan gum coating composition thereof whereby the aqueous gellan gum coating composition is applied in an adherent fashion to a placebo or a tablet containing an active to form a gellan gum coated placebo or gellan gum coated active. Excerpt(s): This invention relates generally to tablet coating(s) on active drugs and to a method to prepare compositions useful to coat active drugs. More particularly this invention relates to a drug coated with gellan gum, a method to prepare a gellan gum composition useful to coat an active drug, a gellan gum composition useful to coat an active drug(s), and to a method for coating active drugs(s) with gellan gum. In particular this invention relates to an intact active tablet comprising an active ingredient selected from the group consisting of aspirin, naproxen sodium, acetaminophen, ibuprofen, celecoxib, oxaprozin, sildenafil citrate, alendronate sodium, mixtures thereof and the like and optimally an analgesic in combination with one or more of an antihistamine, antitussive, decongestant, and expectorant and mixtures thereof and the like, coated with gellan gum, a method to prepare a gellan gum composition useful to coat one or more of the aforementioned actives, mixtures thereof and the like, and to a method for coating one or more of the aforementioned actives, mixtures thereof and the like, with gellan gum. Tablets are typically used to deliver a pharmacologically effective amount of a therapeutic active (drug) to humans and animals so as to provide medicinal benefit
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to the human or animal. Typically such therapeutically effective drugs include those drugs that possess and produce desirable drug effects after effective consumption by the human or animal. Effective consumption is achieved by oral or rectal administration to a patient for example. In medicinal uses, one or more coatings is desired on a medicinal tablet in order to obtain one or more of gloss, better appearance, identification, mouthfeel, stability, color, swallowability, improved taste and the like. Web site: http://www.delphion.com/details?pn=US06485747__ •
Composition for treating pain Inventor(s): Mitch; Charles H. (Columbus, IN), Shannon; Harlan E. (Carmel, IN) Assignee(s): Eli Lilly and Company (indianapolis, In) Patent Number: 5,998,434 Date filed: June 4, 1998 Abstract: The present invention provides a composition and method for treating pain using Selected Muscarinic Compounds and one or more compounds selected from the group consisting of Nonsteroidal Anti-inflammatory drugs, acetaminophen, opioids, and alpha-adrenergic compounds. Excerpt(s): The present invention relates to a method for using a combination of compounds for treating pain. This invention relates to a therapeutic combination of compounds to provide analgesic activity. More active analgesic combinations effects are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages, thereby diminishing the expected side effects and toxicity that would otherwise result from higher dosages. It would be particularly desirable to acquire a synergistic combination effect. Such a composition is the subject of the present invention. Web site: http://www.delphion.com/details?pn=US05998434__
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Compositions and method for treatment of acetaminophen intoxication Inventor(s): Mabley; Jon (Beverly, MA), Salzman; Andrew L. (Belmont, MA), Szabo; Csaba (Glouster, MA) Assignee(s): Inotek Corporation (beverly, Ma) Patent Number: 6,281,222 Date filed: August 17, 2000 Abstract: The invention provides compositions and methods for treatment of acetaminophen intoxication using an inhibitor of xanthine oxidase that does not induce superoxide radical formation when introduced into a subject. An example of a xanthine oxidase inhibitor that can be used according to the invention is AHPP. Excerpt(s): The invention relates to compositions and methods for treating or preventing acetaminophen intoxication. Acetaminophen is a mild analgesic and anesthetic that is safe and effective when ingested in therapeutic doses. Overdoses of acetaminophen, however, can lead to long-term health problems and can even be fatal. For example, overdoses of acetaminophen can lead to acute liver failure which may be associated with multi-organ failure, nephrotoxicity and occasionally pancreatitis. Acetaminophen
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intoxication can also occur in individuals with, e.g., impaired hepatic function, renal disease, chronic alcoholism, or malnutrition. Damage caused by high doses of acetaminophen can manifest itself by elevated serum levels of the liver enzymes aspartate transaminase (AST) and alanine aminotransferase (ALT). Web site: http://www.delphion.com/details?pn=US06281222__ •
Compositions and methods for relieving headache symptoms in aspirin-sensitive headache sufferers Inventor(s): Frank-Kollman; Mary Theresa (173 Egrets Way, Richmond Hill, GA 31324) Assignee(s): None Reported Patent Number: 6,440,983 Date filed: December 21, 2000 Abstract: The treatment of migraine and/or cluster headaches in human beings in need of such treatment includes oral administration of a composition containing acetaminophen, ibuprofen, caffeine and magnesium as the active ingredients. The inclusion of an additional active ingredient, guaifenesin, further provides treatment for severe sinus headaches. Compositions and methods for alleviating the symptoms of these headache conditions are disclosed. Excerpt(s): The present invention relates broadly to the field of healthcare, and in particular, to the treatment of severe headaches in human beings. More specifically, this invention relates to compositions and methods for providing relief from the symptoms of migraine headaches and/or cluster headaches and/or headaches related to sinus congestion, in affected individuals who also have a low tolerance for aspirin due to digestive disorders. Migraine is a particularly painful headache, which recurs and can be physically debilitating to sufferers. In many respects, cluster headaches are similar to migraine headaches, and all references herein to migraine and/or migraine headaches shall be considered as also including, and as references to, cluster headaches. There is no single cause or remedy for migraine headaches, and the incidence of migraine appears to be increasing in the general population. Although sufferers, on average, experience only one attack per month, each attack can last between four and seventy-two hours. In some cases, sufferers experience a pre-onset "warning" which may indicate that a migraine is imminent, and which may be termed an "aura." An "aura" is a disruption of brain function characterized by visual disturbances like flashing lights and blurred vision. These "disruptions" occur twenty to thirty minutes before an attack. About twenty percent of migraine suffers experience "aura" symptoms. Other attacks can be preceded by a "prodrome" several hours before the onset of a migraine. These "prodrome" symptoms may include, but are not limited to, fatigue, yawning, sensory sensitivity, mood changes, and food cravings. Prescription medications have previously been developed to alleviate the severity of migraine pain, but prescription migraine medications generally contain some type of narcotic, which, over time, may become addictive. Although over-the-counter remedies also exist, marketed under the EXCEDRIN.RTM. and ADVIL.RTM. brands, the EXCEDRIN.RTM. Migraine Formula contains aspirin, acetaminophen, and caffeine as its active ingredients, while the only active ingredient of the ADVIL.RTM. Migraine product is ibuprofen. Many migraine sufferers cannot take aspirin, due to digestive disorders, such as acid reflux disease, ulcers, and acid indigestion, and for many such sufferers, ibuprofen alone is not sufficient to lessen the pain or to reduce it to a manageable level. It would therefore be
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desirable to provide a non-prescription remedy which alleviates migraine symptoms in a manner not accomplished by the currently available "over-the-counter" remedies. Web site: http://www.delphion.com/details?pn=US06440983__ •
Compositions containing the nonprescription combination of acetaminophen, aspirin and caffeine to alleviate the pain and symptoms of migraine Inventor(s): Armellino; Joseph (Chester, NJ), Koslo; Randy (West Windsor Township, NJ) Assignee(s): Bristol-myers Squibb Company (new York, Ny) Patent Number: 5,972,916 Date filed: February 10, 1998 Abstract: The invention provides a safe and economical nonprescription combination of acetaminophen, aspirin and caffeine (APAP/ASA/CAF) for use in treating migraine pain and the cluster of symptoms characteristic of migraine attack, such as nausea, photophobia, phonophobia and functional disabilities. The use of the APAP/ASA/CAF combination is also effective in aborting the prodrome phase of a migraine attack. Excerpt(s): The present invention relates generally to compositions and methods used to alleviate the symptoms and pain associated with acute migraine attack. More particularly, the present invention relates to the use of a nonprescription combination of acetaminophen, aspirin and caffeine for treating individuals afflicted with pre-migraine conditions, migraine-associated symptoms and/or migraine pain of mild to severe intensity. An estimated 23 to 25 million Americans--about 18% of women and 6% of men--suffer from migraine pain and migraine-related symptoms.sup.1. Attacks are common, with more than 50% of sufferers experiencing one or more episodes per month.sup.2. Migraine, a heterogeneous disorder, produces a wide spectrum of pain and associated disabilities, both within and among individual sufferers. The spectrum includes mild pain and no disability in approximately 5-15% of migraine attacks, moderate to severe pain and disability in approximately 60-70% of attacks, and incapacitating pain and total disability in the remaining approximately 25-35% of attacks.sup.3,4. Web site: http://www.delphion.com/details?pn=US05972916__
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Concentrated acetaminophen solution compositions Inventor(s): Dhabhar; Dadi J. (Cincinnati, OH) Assignee(s): The Procter & Gamble Company (cincinnati, Oh) Patent Number: 5,510,389 Date filed: March 2, 1994 Abstract: Improved concentrated liquid pharmaceutical compositions containing acetaminophen wherein said acetaminophen is formed by adding a Beckman rearrangement catalyst to 4-hydroxyacetophenone oxime. Excerpt(s): The present invention relates to improved concentrated liquid pharmaceutical compositions containing acetaminophen as well as a process for their manufacture. Liquid, and especially concentrated liquid pharmaceutical compositions
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containing acetaminophen in solution offer several advantages over solid compositions. Liquids are easy to swallow and provide an excellent vehicle for the uniform delivery of pharmaceutical actives. Moreover, liquids provide a rapid onset of pharmacologic action, since the composition does not first have to disintegrate and dissolve in the gastrointestinal tract. Likewise, concentrated liquid compositions offer certain distinct advantages. These compositions are ideally suited for incorporation into easy-toswallow soft, flexible capsules. Encapsulation of this nature permits the accurate and uniform delivery of unit dose amounts of a pharmaceutical active, encompassing even those instances where relatively small amounts of a pharmaceutical active are to be delivered. In addition, soft gelatin capsules are aesthetically appealing (especially when filled with a transparent liquid) and can be manufactured in a wide variety of sizes, shapes, and colors. These advantages notwithstanding, it is often difficult to prepare such compositions using the desired pharmaceutical active however. Acetaminophen is poorly soluble and, therefore, require relatively large volumes of solvent for dissolution, resulting in impractically large doses. Also, encapsulating such large volumes into easyto-swallow gelatin capsules presents obvious difficulties, suggesting the immediate importance of concentrated liquid compositions. Furthermore, the situation becomes even more complicated when multiple pharmaceutical actives are involved. Web site: http://www.delphion.com/details?pn=US05510389__ •
Dry analytical element for acetaminophen assay Inventor(s): Arter; Thomas Charles (Rochester, NY), Mauck; John Charles (Rochester, NY), Schaeffer; James Robert (Penfield, NY), Winterkorn; Robert Francis (Rochester, NY) Assignee(s): Clinical Diagnostic Systems, Inc. (rochester, Ny) Patent Number: 6,015,683 Date filed: July 15, 1992 Abstract: A spectrophotometric assay for the detection of acetaminophen in aqueous fluids can be carried out with a dry analytical element. The element comprises a support having thereon one or more reagent layers containing a first enzyme, aryl acylamidase, to cleave the amide bond of acetaminophen to produce p-aminophenol; a second enzyme, ascorbic acid oxidase, to oxidize the p-aminophenol so that it couples to a water soluble coupling agent to form a dye that is read at 670 nm. The assay is precise, accurate on serum and plasma samples, and relatively free from significant interferences. The element also allows measurement over a broad dynamic range. Excerpt(s): This invention relates to the field of clinical chemistry. Acetaminophen is a widely used analgesic. It is available without a prescription and is often used when aspirin may present problems to a patient. At therapeutic doses, serum concentration is usually below 50 mg/L. Toxicity is usually observed if the serum concentration four hours after ingestion of the drug is greater than 300 mg/L. One effect of overdose is liver toxicity. The need for an accurate method of determining the concentration of acetaminophen in serum is therefore apparent. Known methods of assaying anilides such as acetaminophen utilize arylacylamidase (E.C.3.5.1.13) and an oxidizing agent. Arylacylamidase cleaves the amide bond of the anilide to produce acetate and an aniline such as p-aminophenol. The aniline is then made to react with with a color-forming compound like phenol in the presence of an oxidizing agent such as permanganate or the metal salts of copper or iron to form a color compound like indophenol which can be detected at 615 nm. Other methods use oxidizing agents like periodate, persulfates, or peroxidase. U.S. Pat. Nos. 4,999,288 and 4,430,433 are typical.
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Web site: http://www.delphion.com/details?pn=US06015683__ •
Enzyme electrode sensor and manufacturing method thereof Inventor(s): Kim; Youn Tae (Taejon, KR), Yang; Haesik (Taejon, KR) Assignee(s): Electronics and Telecommunications Research Institute (taejon, Kr) Patent Number: 6,413,396 Date filed: February 4, 2000 Abstract: An enzyme electrode sensor and a fabricating method thereof, and more particularly, an enzyme electrode sensor which is a biosensor using electrochemical measurement and a manufacturing method thereof. The sensor includes an electrode, a first nonconducting polymer layer formed by electropolymerization outside the electrode wherein enzyme is immobilized in the nonconducting polymer layer, a second nonconducting polymer layer in which enzyme is not immobilized, the second nonconducting layer formed by electropolymerization outside the first nonconducting polymer layer, and an outer layer formed outside the second nonconducting layer. The sensor selectivity is improved as the interference of organic materials is inhibited, and the interference of acetaminophen causing the major problem with a glucose sensor is controlled effectively by the sensor. Excerpt(s): The present invention relates to an enzyme electrode sensor and a fabricating method thereof, and more particularly, to an enzyme electrode sensor which is a biosensor using electrochemical measurement and a manufacturing method thereof. Research has focused on developing a multi-functional small-sized sensor, e.g., a biosensor of which selectivity is excellent, and of which precision is excellent as health and environment become personal major concerns. A biosensor introducing enzyme and electrochemical measurement has been developed widely. In this case, the enzyme includes glucose oxidase, lactate oxidase, alcohol oxidase, cholesterol oxidase, and the like. Web site: http://www.delphion.com/details?pn=US06413396__
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Extended release acetaminophen particles Inventor(s): Anaebonam; Aloysius O. (Burlington, MA), Clemente; Emmett (Manchester, MA), Fawzy; Abdel A. (Dracut, MA), Mendes; Robert W. (Dedham, MA), Morrel; Eric M. (Medfield, MA) Assignee(s): Ascent Pediatrics (wilmington, Ma) Patent Number: 6,126,967 Date filed: September 3, 1998 Abstract: An extended release acetaminophen composition comprises a plurality of discrete particles containing acetaminophen which, when contained within a gelatin capsule and assayed in a USP Apparatus I rotating basket at 50 rpm in 900 mL of phosphate buffer at pH 5.8 and 37.degree. C., exhibits about 40 percent to about 53 percent acetaminophen dissolution at one-half hour, about 50 percent to about 68 percent dissolution at 45 minutes, about 57 percent to about 77 percent acetaminophen dissolution at one hour, and about 82 percent to about 92 percent acetaminophen dissolution at two hours. After six hours, the contemplated extended release
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acetaminophen composition exhibits substantially complete dissolution. A process for treating a human patient with the extended release acetaminophen composition is also disclosed. Excerpt(s): This invention relates to the extended release administration of medication. More particularly, the invention relates to an acetaminophen composition that has particular in vitro acetaminophen release characteristics and is adapted for use by human patients that have difficulty swallowing acetaminophen tablets or capsules. Coating medication to effect a controlled or extended release administration profile is well known in the art. Drug manufacturers have been using such methods to provide oral administration of medications that enter the body over a predetermined, extended period of time. Controlled release administration provides many benefits to a patient. For example, controlled release administration can reduce the number of times that a patient is required to self-administer medication, thus reduce the possibility that the patient will forget to take his or her medication during the day Analgesics and antipyretics, such as acetaminophen are often self-administered over the course of a day to help alleviate pain or fever from which a person is suffering. Often, such symptoms can last for long periods of time. However, the symptoms need not affect the person's typical daily routine. Thus, the person may not remember to take his or her medication because of other daily activities. Web site: http://www.delphion.com/details?pn=US06126967__ •
Gelatin capsules containing a highly concentrated acetaminophen solution Inventor(s): Linkin; Deborah (Madeira Beach, FL), Shelley; Rickey S. (Largo, FL), Wei; Youching (Clearwater, FL) Assignee(s): R. P. Scherer Corporation (troy, Mi) Patent Number: 5,505,961 Date filed: June 22, 1994 Abstract: A method is disclosed for increasing the solubility of acetaminophen alone or in combination with antihistamines, antitussives, decongestants, and expectorants to form a clear solution for encapsulation into a softgel. The acetaminophen is solubilized alone or in combination with the above ingredients by mixing with polyethylene glycol, propylene glycol, water, polyvinylpyrrolidone and potassium (or sodium) acetate. This invention increases the solubility of the acetaminophen to obtain the same size softgel for a 325 mg dose as is presently available for a 250 mg dose softgel product. The disclosed solvent system is useful because it provides for a highly concentrated solution of acetaminophen capable of encapsulation in a small enough capsule to permit easy swallowing. Excerpt(s): The present invention relates to soft and hard shell gelatin capsules encapsulating a pharmaceutically acceptable fill containing acetaminophen. Soft gelatin capsules or softgels are predominantly used to contain liquids wherein the active ingredients are present in the dissolved or suspended state. Filled one-piece softgels have been widely known and used for many years and for a variety of purposes. Because softgels have properties that are quite different from telescoping two-piece, hard shell capsules, the softgels are capable of retaining a liquid fill material. The fill material may vary from industrial adhesives to bath oils. More commonly, however, the softgels are used to enclose consumable materials such as vitamins and pharmaceuticals in a liquid vehicle or carrier. A particularly good bioavailability of the
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pharmacologically active substance is attained if the active substance is successfully dissolved in a suitable solvent and the encapsulated solution is administered to the patient. The term "active substance" as used herein describes any active substance that can be orally administered in capsule form. This term includes pharmaceuticals, dietary supplements, vitamins and the like. Web site: http://www.delphion.com/details?pn=US05505961__ •
Glycoside derivatives of acetaminophen Inventor(s): Houston; Todd A. (Timonium, MD), Klemke; R. -Erich (Hilzingen, DE), Koreeda; Masato (Ann Arbor, MI), Shull; Brian K. (Ann Arbor, MI), Tuinman; Roeland J. (Fenton, MI) Assignee(s): Harrier Inc. (hermosa Beach, Ca) Patent Number: 5,693,767 Date filed: June 1, 1994 Abstract: Novel glycosides, especially steroidal and non-steroidal glycosides are provided. The steroidal and non-steroidal glycosides preferably are prepared from aglycons which possess valuable properties such as pharmacological properties. The glycosides are prepared from useful aglycons and possess useful properties which are the same as those of their respective unglycosylated aglycons. The glycosides are provided in acylated and deacylated form. The acylated glycosides after hydrolysis of the acyl groups possess enhanced water solubility properties, as illustrated in the case where the aglycon is acetominophen. Excerpt(s): This invention relates to a surprisingly novel method for the production of a broadly novel type of glycosides. The method comprises glycosylation (i.e., glycosidation) of an aglycon compound having a functional group, e.g., a hydroxy compound such as a hydroxy-steroid or hydroxy-non-steroid. The invention also importantly relates to the resulting glycosides as novel compounds of diverse application having desired properties including pharmacodynamic properties; and to medicaments containing the compounds. The glycosylation of alcohols or phenols and particularly glycosylation of hydroxy-steroids, is known per se. However, glycosylation often produces undesired ortho esters as described, e.g., in Chemical Abstracts, Vol. 105, 1986, 172882s. A method which minimizes the content of the unwanted ortho ester is disclosed in Chemical Abstracts, Vol. 104, 1986, 22511g (Liebigs Ann. Chem. 1986, 717730). However, this method again does not completely avoid the formation of ortho esters. Further, the method requires the use of pivaloylglucopyranosylbromide wherein the pivaloyl groups function as protecting groups to suppress the formation of ortho esters. The reaction of the glycoside with the steroid proceeds by means of silver oxide or silver carbonate catalysts. The use of.alpha.-halo tetraacetylglucosides which are commonly used for the glycosylation of steroids, especially of cholesterol, requires the use of expensive or toxic reaction catalysts, such as Ag.sub.2 O, Ag.sub.2 CO.sub.3, PbCO.sub.3, Hg(CN).sub.2, etc. This as a practical matter prohibits its technical application on a large scale. Furthermore, these glycosylation procedures generally constitute multistage processes which also lead to an unwanted mixture of.alpha.and.beta.-glycosylation. Web site: http://www.delphion.com/details?pn=US05693767__
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Granulation process for producing an acetaminophen and diphenhydramine hydrochloride composition and composition produced by same Inventor(s): Eisenhardt; Peter F. (Philadelphia, PA), Hitchner; Robert (Perkasie, PA), Parekh; Kishor B. (Horsham, PA) Assignee(s): Mcneil-ppc, Inc. (skillman, Nj) Patent Number: 5,635,208 Date filed: July 20, 1993 Abstract: A granulation process for preparing a solid dosage form containing acetaminophen and diphenhydramine hydrochloride, as active agents is disclosed. In addition, the solid dosage form produced by the process is described. Excerpt(s): Products containing the analgesic acetaminophen and the sleep aid diphenhydramine hydrochloride have been marketed for a number of years. Such products are marketed in various final solid dosage forms including tablets, caplets and gelcaps. The process used to produce solid dosage forms which are then formed into a final solid dosage form generally comprises a single granulation process wherein acetaminophen and diphenhydramine hydrochloride together with certain excipients are dry blended and then granulated by spraying the dry blended material with a suitable binder such as starch while the dry blend is mixed in a granulator such as a Fielder granulator. The granulation so formed is then dried, milled and formed into one of a number of solid dosage forms by conventional processing. As used herein the term "solid dosage form" means the solid core component of a dosage form, which may then be processed into a final solid dosage form. In the case of a caplet, it is the core caplet without any coating. In the case of a gelcap, it is the core caplet without any precoat or gelatin coating. In the case of a tablet, it is the core tablet without any coating. Generally, the solid dosage form is the core component formed from a conventional compressing step of the granulation before it undergoes any further processing. The term "final solid dosage" form means a solid dosage form, which has undergone further processing, such as precoating, coating, gelatin coating, printing or the like. The acetaminophen/diphenhydramine hydrochloride solid dosage forms produced by this process possess inadequate hardness, generally about 7 kp or less. As a result, the solid dosage forms may become damaged during processing and packaging. This creates quality control problems and increases production costs. Another problem with this process is that the solid dosage forms produced possess a relatively high friability of greater than 1.0%. Accordingly, it is an object of the present invention to develop a process which produces a medicament which when made into a solid dosage form has an adequate hardness of greater than 7 kp and preferably of from about 9-12 kp and a friability of less than about 1%. Web site: http://www.delphion.com/details?pn=US05635208__
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Immediate release tablet cores of acetaminophen having sustained-release coating Inventor(s): Chasin; Mark (Manalapan, NJ), Oshlack; Benjamin (New York, NY) Assignee(s): Euro-celtique S.a. (luxembourg, Lu) Patent Number: 6,210,714 Date filed: February 14, 2000
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Abstract: A controlled release tablet for oral administration is disclosed which has a tablet core including an insoluble therapeutically active agent having an aqueous solubility of less than or equal to about 5 mg/ml in a sufficient amount to render a therapeutic effect. The core provides rapid release of said therapeutically active agent upon exposure to aqueous solutions. The tablet core is coated with a controlled release coating permitting sustained release of said therapeutically active agent when said coated tablet is exposed to aqueous solutions. Excerpt(s): The maximum time of effectiveness of many oral dosage forms is only a few hours. In order to maximize patient compliance, it is considered very desirable to reduce the frequency of dosing, thereby reducing the number dosage forms (e.g., tablets, etc.) a patient must take in order to attain effective therapy. Sustained release formulations for drugs have become increasingly available. This is true especially when the particular drug is relatively soluble. Various formulation techniques have been used for providing a sustained release formulation of soluble drugs. In many such formulations, a drugcontaining particle is coated with a coating layer or is dispersed within a continuous matrix such as a polymeric matrix. The coating layer or the matrix Comprises a relatively insoluble material or materials, and the release of the drug is controlled by means of the resistance of the coating layer or matrix against the diffusion of the drug therethrough. The release of the drug from such formulations is driven, e.g., by the gradient of the drug concentration resulting from penetration of, e.g., gastric fluid, by diffusion into the formulation. The task of preparing controlled release formulations of relatively insoluble drugs has proven to be more difficult, however. Examples of such relatively insoluble drugs include acetaminophen, naproxen and indomethacin. Web site: http://www.delphion.com/details?pn=US06210714__ •
Method for the purification of acetaminophen Inventor(s): Fruchey; Olan Stanley (Bad Soden/T.S., DE), Wheeler; Larry O. (Corpus Christi, TX), Zey; Edward G. (Corpus Christi, TX) Assignee(s): Basf Corporation (mount Olive, Nj) Patent Number: 5,981,799 Date filed: March 15, 1994 Abstract: A method is provided for purifying a crude N-acetyl-para-aminophenol (APAP) containing color bodies or their precursors, the method comprising: a) forming a hot aqueous solution of the crude APAP; and b) subsequently contacting the hot solution with an acid washed adsorbent carbon, e.g., an activated carbon, which acid washed carbon, prior to such contact, has been pretreated by contacting it with an aqueous solution of a reducing sulfite. Excerpt(s): This invention relates to an improved method for the purification of Nacetyl-para-aminophenol (APAP), also known as acetaminophen. APAP is a wellknown over-the-counter analgesic and anti-pyretic agent. The following prior art references are disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98. U.S. Pat. No. 3,042,719, issued Jul. 3, 1962 to Hahn et al., discloses the purification of crude discolored APAP by acidifying an aqueous solution of the APAP with a mineral acid, filtering the solution while hot, and cooling the filtrate while adding an alkaline reducing sulfite, e.g., sodium hydrosulfite (sodium dithionite). A "decolorizing" carbon may be added to the hot solution. Web site: http://www.delphion.com/details?pn=US05981799__
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Method of treating acetaminophen overdose Inventor(s): Hausheer; Frederick H. (203 Kendall Pkwy., Boerne, TX 78229), Peddaiahgari; Seetharamulu (1207 Fawn Haven, San Antonio, TX 78248) Assignee(s): None Reported Patent Number: 6,225,295 Date filed: September 27, 2000 Abstract: A method of treating patients suffering from acetaminophen overdose is disclosed. The method comprises administering to a patient in need of treatment an effective amount of a thiol or reducible disulfide compound according to the formula set forth in the specification. Excerpt(s): This invention relates to a method for treating a patient suffering from overdose of acetaminophen. The method involves administering an effective amount of a disulfide or thiol-containing compound to a patient suffering from acetaminophen overdose. Acetaminophens are mainly over the counter pain relief medications, and are perhaps the most widely used drugs in the world. One of the most popular brands of the drug is Tylenol.RTM. Acetaminophen is generally regarded as safe for use, although long-term adverse effects can include GI ulcers, nephropathy, anemia, liver damage, and other effects. Adverse effects from accidental overdose can be potentially life threatening and include hepatic necrosis and nephropathy. The risk is increased significantly for chronic alcoholics, for persons who have recently ingested large amounts of alcohol, and for persons with impaired liver or kidney function. Web site: http://www.delphion.com/details?pn=US06225295__
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Method of treating iron overload with acetaminophen Inventor(s): Walker, Jr.; Ernest M. (Huntington, WV) Assignee(s): Marshall University Research Corporation (huntington, Wv) Patent Number: 6,509,380 Date filed: December 14, 2001 Abstract: The present invention relates to methods of controlling iron overload in a patient in need thereof. The present invention particularly relates to methods of treating hemochromatosis and other causes of iron overload. Excerpt(s): The present invention relates to methods for reducing iron levels and/or levels of other toxic metals or elements in mammals. In a particular aspect, the present invention relates to methods for reducing free iron ion levels and/or excess and toxic levels of other elements in mammals, and to the removal of excess iron or excesses of other metals/elements stored in the organs by administration of acetaminophen and/or structural or chemical analogues or derivatives thereof. These compounds may scavenge excess iron or free iron ions in hosts undergoing anthracycline chemotherapy, as well as hosts suffering from iron overload or non-iron overload diseases and/or conditions, such as hereditary hemochromatosis, blood-transfusion related anemias and hemolytic anemias such as thalassemia, hemodialysis, stroke, and rheumatoid arthritis. Acetaminophen is particularly preferred in this regard. In a further aspect, the present invention relates to compositions and formulations useful in the methods disclosed herein. Iron is crucial for maintaining normal structure and function of virtually all mammalian cells (see, for example, Voest et al., in Ann. Intern. Med., 120:490-499 (1994)
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and Kontoghiorghes, G. J., in Toxicol. Letters, 80:1-18 (1995), the contents of which are hereby incorporated by reference in their entirety). Iron and its binding proteins have immunoregulatory properties. Adult humans contain 3-5 g of iron, mainly in the form of hemoglobin (58%), ferritin/hemosiderin (30%), myoglobin (9%) and other heme or nonheme enzyme proteins (Harrison and Hoare, in Metals in Biochemistry, Chapman and Hall, New York, 1980, the contents of which is hereby incorporated by reference in its entirety). Approximately 10 to 15 mg of dietary iron is normally consumed per day by each individual in the U.S. About 1 to 2 mg of iron in the Fe (II) form is absorbed each day chiefly through villi in the duodenum to compensate for the 1 to 2 mg daily body loss of iron. Normal men absorb about 1 mg iron per day, menstruating women 2 mg iron per day, and hemachromotosis patients 2 to 5 mg iron per day. Total iron levels in the body are regulated mainly through absorption from the intestine and the erythropoietic activity of the bone marrow. Upon absorption, iron is transported to various tissues and organs by the serum protein transferrin. Once transported to the target tissue or organ, iron is transported and stored intracellularly in the form of ferritin/hemosiderin. Under normal conditions, transferrin is about 30% saturated with iron in healthy individuals, and an equilibrium is maintained between the sites of iron absorption, storage and utilization. The presence of these homeostatic controls ensures the maintenance of physiological levels of not only iron, but also other essential metal ions such as copper, zinc and cobalt. The control of iron absorption may be genetic with complex interactions with intestinal mucosal cells, dietary factors, and other influences. Web site: http://www.delphion.com/details?pn=US06509380__ •
Methods for determining gluconeogenesis, anapleurosis and pyruvate recycling Inventor(s): Cottam; G. Larry (Richardson, TX), Jeffrey; F. M. H. (Dallas, TX), Jones; John G. (Dallas, TX), Malloy; Craig. R. (Dallas, TX), Sherry; A. Dean (Dallas, TX) Assignee(s): Board of Regents, the University of Texas System (austin, Tx) Patent Number: 6,329,208 Date filed: July 16, 1998 Abstract: Simple equations that relate glucose, glutamate, glucuronate, and phenylacetylglutamine.sup.13 C NMR multiplet areas to gluconeogenesis and pyruvate recycling during metabolism of [1,2,3-.sup.13 C.sub.3 ]propionate are presented. This indicates that a direct measure of gluconeogenesis, pyruvate recycling, and anaplerosis may be obtained from a single.sup.13 C NMR spectrum of suitably prepared blood or urine samples collected after oral administration of enriched propionate, acetaminophen, and phenylacetate. Excerpt(s): The invention relates to convenient and efficient methods of assay and diagnosis of metabolic states, particularly gluconeogenesis, pyruvate flux and anapleurosis. Current methods for the measurement of gluconeogenesis in humans require exposure to radioactive materials. Unfortunately, this feature precludes almost any quantitative studies of these pathways in patients. The development of.sup.13 C NMR for clinical applications is very attractive because of its convenience and the dramatic improvement in metabolic detail which it can provide. Although direct in vivo NMR spectroscopy is the most exciting application for.sup.13 C tracer studies, it is unlikely that appropriate whole-body systems will be widely available any time soon for clinical research. On the other hand, analytical NMR spectrometers suitable for.sup.13 C NMR studies of human blood or urine are already in place in every medical school in this country. Measurement of hepatic gluconeogenesis using both.sup.13 C
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and.sup.14 C-labeled glucose is by now a well-developed approach and had been successfully applied in both animals and humans. However, measurements of absolute anaplerotic fluxes have been largely restricted to perfused organs and tissues and the methods cannot be performed in vivo. Since only gluconeogenesis can currently be measured noninvasively, a necessary simplification is to assume that gluconeogenesis is equal to anapleurosis. The penalty for this assumption is that the total anaplerotic flux is underestimated to an unknown degree, and the allocation of anaplerotic carbons between gluconeogenesis and the other biosynthetic pathways is not known. Web site: http://www.delphion.com/details?pn=US06329208__ •
Methods for treating and preventing HIV infection using acetaminophen and derivatives thereof Inventor(s): Bourinbaiar; Aldar S. (New York, NY) Assignee(s): Metatron, Inc. (deer Park, Ny) Patent Number: 5,837,729 Date filed: April 26, 1996 Abstract: The present invention relates to the use of acetaminophen (Tylenol) and derivatives thereof which can be used to inhibit the growth, replication and elaboration of the human immunodeficiency virus (HIV). The present invention comprises in vitro as well as in vivo methods for the prevention and/or treatment of HIV infections and acquired immune deficiency syndrome (AIDS), at doses of acetaminophen or its derivatives which are effective to inhibit the replication, growth and/or elaboration of HIV. Excerpt(s): The present invention is directed to methods of preventing and treating HIV infections using acetaminophen and pharmaceutically acceptable derivatives thereof. The present invention relates to the discovery that acetaminophen and a number of pharmaceutically acceptable derivatives, thereof may be used to inhibit the growth, replication and elaboration of HIV in humans. This invention is useful for treating and/or preventing retroviral infections such as HIV infections and the underlying immunodeficiency state known as AIDS. Human immunodeficiency viruses (HIV) of type 1 and 2 belong to the family of retroviruses and are considered to cause acquired immunodeficiency syndrome (AIDS). Human T lymphotropic viruses (HTLV) of type 1 and 2 are also human retroviruses and cause adult T cell leukemia and neurodegenerative diseases. Thus, there are several types of pathogenic retroviruses which can be harmful to humans. The transmission of HIV through sexual contact accounts for up to 90% of AIDS cases worldwide. This transmission is initiated by the passage of HIV across the mucosal barrier of the vagina, penis or rectum when exposed to infectious genital fluids such as semen or vaginal secretions. Increased public awareness of the sexual modes of HIV transmission has been of little consequence in reducing or curbing the AIDS epidemic. Although research activity in the area of finding effective anti-HIV agents has increased in recent years, effective compounds with anti-HIV activity that could be used to prevent transmission and/or treat HIV infections are still lacking. For example, early results with certain spermicidal agents, e.g., the nonionic surfactant, nonoxynol-9, appeared to be quite promising, but it has become clear that local toxicity of this agent is incompatible with its antiviral activity when used at an effective concentration. This shortcoming is due to the fact that the selective index (i.e., the ratio of cytotoxicity to antiviral activity as a function of drug concentration) of nonoxynol-9 (Bourinbaiar & Fruhstorfer AIDS, 10:14, 1996). Similar
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toxicity concerns have arisen with the broad use of azidothymidine (AZT). A number of nucleoside and non-nucleoside compounds which exhibit activity against retroviral reverse transcriptase, have been posited for the treatment of AIDS, but are not without their limitations. In addition, recently introduced new drugs, such as HIV protease inhibitors, are difficult to manufacture and have shown low oral availability which requires frequent intake of large doses. Consequently, the present methods of preventing and treating HIV are limited and better alternative compounds with higher availability and selectivity must be sought. Web site: http://www.delphion.com/details?pn=US05837729__ •
Migraine medicine and method for treating same Inventor(s): Imanzahrai; Ashkan (1642 Nord La., San Jose, CA 95125) Assignee(s): None Reported Patent Number: 6,642,243 Date filed: June 14, 2000 Abstract: This invention is a safe and effective composition and method for treating acute migraine attacks using pseudoephedrine, acetaminophen, and other agents in an orally administrated form to alleviate the pain and cluster of symptoms characteristic of migraine attacks such as nausea, photophobia, phonophobia, and functional disabilities as well as the prodrome phase of a migraine attack. Excerpt(s): The present invention relates generally to compositions and methods used to alleviate the symptoms and pain associated with an acute migraine attack. Many migraine sufferers use single-agent nonprescription analgesics such as acetaminophen, or aspirin, or non-steroidal anti-inflammatory agents to treat their attacks. (Lipton R B, Newman L C, Solomon S. Over-the-counter medication and the treatment of migraine. Headache 1994; 34:547-548.) In other countries, a number of nonprescription drugs are specifically approved for migraine pain. (Lipton R B, Newman L C, Solomon S. Overthe-counter medication and the treatment of migraine. Headache 1994; 34:547-548.) The effectiveness of self-treatment of a migraine and the effectiveness of most such nonprescription drugs in relieving or aborting migraine pain and/or the characteristic symptoms of a migraine has not been adequately studied in well-controlled clinical trials. (Lipton R B, Newman L C, Solomon S. Over-the-counter medication and the treatment of migraine. Headache 1994; 34:547-548.) Acetaminophen, aspirin, and caffeine are approved for relief of nonspecific headaches and tension headaches (Migliardi J R, Armellino J J, Friedman M, Gillings D B, Beaver W T. Caffeine as an analgesic adjuvant in tension headache. Clin Pharmacol Ther 1994; 56:576-586), which are clinical and physiologically distinct from a migraine. Caffeine is widely consumed and has also been indicated for use to treat asthma, drowsiness, fatigue, lumbar puncture headache, and neonatal apnea. [(Reents S. Clinical Pharmacology. Gold Standard Multimedia, Inc. (www.gsm.com) 1999. Available from URL:https://home.po.com.)] Caffeine is also an analgesic adjuvant for a variety of pain conditions and has been included in combination with other analgesics, ergot alkaloids, and barbiturates in prescription formulations for a migraine. (Laska E M, Sunshine A, Mueller F, Elvers W B, Siegel C, Rubin A. Caffeine as an analgesic adjuvant. JAMA 1984; 251:1711-1718; Olesen J. A review of current drugs for migraine. J Neurology 1991; 238 Suppl 1:S23-S27; Solomon G D. Therapeutic advances in migraine. J Clin Pharmacol 1993; 33:200-209; and Sawynok J. Pharmacological rationale for the clinical use of Caffeine. Drugs 1995; 49:37-50.) Caffeine itself may act to relieve a migraine. Caffeine
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has shown to reduce cerebral blood flow in humans and to be a nonselective adenosine receptor antagonist. Reduction of cerebral blood flow may be due to caffeine inhibition of the adenosine A2 receptor. (Sawynok J. Pharmacological rationale for the clinical use of Caffeine. Drugs 1995; 49:37-50.) A2 receptors are on cerebral vascular muscles, and act to cause vasodilation. Hence, their inhibition would have the effect of vasoconstriction similar to other medications used to abort the migraine headache. Web site: http://www.delphion.com/details?pn=US06642243__ •
Pharmaceutical compositions with analgesics containing codeine Inventor(s): Uribe; Jose R. (24 Whitewood Dr., Morris Plains, NJ 07950) Assignee(s): None Reported Patent Number: 6,127,352 Date filed: September 22, 1992 Abstract: Compositions for the relief of pain containing acetyl salicylic acid or acetaminophen as a peripherally acting analgesic and codeine as a centrally acting agent. Excerpt(s): This Invention relates to novel pharmaceutical compositions containing codeine and particularly to such compositions having reduced side effects while relieving pain with more efficiency. The analgesic compositions generally used for relieving a large variety of pain states contain two levels of codeine as the central acting agent and as the peripherally acting agent(s) acetaminophen or acetyl salicylic acid or combinations of these two agents. The most universal combinations come in two forms of either 30 or 60 mg of codeine with 300 mg of acetaminophen or 325 mg of acetyl salicylic acid. The most common composition contains the smaller amount of codeine since the larger the amount of codeine, the severer the side effects. It is the general belief that the smaller amount of codeine the less effective is the composition as an analgesic. However, there are compositions available with 300 mg of acetaminophen or acetyl salicylic acid and lower amounts of codeine such as 7.5 mg and 15 mg which are used for children or patients with small body weight. Nevertheless, over 99% of the use of "Codeine Combinations" consists of combinations including 30 or more mg of codeine, and the combination of 30 mg of codeine with 300 mg of acetaminophen represents about 90% of all usage of codeine combinations, reason for which we call it the "state of the art Codeine Combination". U.S. Pat. No. 2,889,249 issued to Beiler et al. discloses a combination of codeine and aspirin with.alpha.-allyl-.alpha.-benzylacetamide. The most pertinent prior art is the combinations of codeine recited above. Web site: http://www.delphion.com/details?pn=US06127352__
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Prevention and amelioration of liver toxicity with beta-carotene Inventor(s): Baranowitz; Steven (85 Tices La. - Apt. 39, New Brunswick, NJ 08816), Maderson; Paul F. (Box 6, 210 Axhandle Rd., Rd. 3, Quakertown, PA 18951) Assignee(s): None Reported Patent Number: 5,670,549 Date filed: June 30, 1995
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Abstract: A method for preventing acetaminophen toxicity in a mammal is provided. An acetaminophen toxicity inhibiting amount of beta-carotene is administered before, simultaneously with, after, or any combination thereof, administering acetaminophen to the mammal. Methods for reducing acetaminophen toxicity in a mammal in need of such treatment and for increasing the maximum amount of acetaminophen that can be administered to a mammal without the mammal exhibiting acetaminophen toxicity are also provided. Acetaminophen toxicity reducing amounts and acetaminophen toxicity preventing amounts, respectively, are administered. In another embodiment, a nonsteroidal analgesic and anti-inflammatory composition of acetaminophen and an acetaminophen toxicity preventing amount of beta-carotene is provided. Excerpt(s): The invention relates to a method for the prevention or the treatment of acetaminophen toxicity in a mammal in need of such treatment and to a method for increasing the maximum non-toxic dosages of acetaminophen that can safely be administered to a mammal. Beta-carotene is administered in appropriate amounts. Compositions and dosage forms of acetaminophen with appropriate amounts of betacarotene are disclosed as well. Acetaminophen is a commonly used, non-steroidal analgesic agent that is available in over one hundred prescription and over-the-counter formulations. While acetaminophen has fewer gastro-intestinal side effects than aspirin, another commonly used non-steroidal analgesic agent, acute and chronic acetaminophen toxicity can result in gastro-intestinal symptoms, severe liver damage, and even death. Web site: http://www.delphion.com/details?pn=US05670549__ •
Prevention and treatment proanthocyanidin extract
of
acetaminophen
toxicity
with
grape
seed
Inventor(s): Bagchi; Debasis (Omaha, NE), Ray; Siddhartha D. (Milltown, NJ) Assignee(s): Dry Creek Nutrition, Inc. (modesto, Ca) Patent Number: 6,245,336 Date filed: March 11, 1999 Abstract: A method for preventing and/or reducing the toxicity of acetaminophen is disclosed. An amount of grape seed proanthocyanidin extract effective to inhibit toxicity of acetaminophen is administered before, simultaneous with, and/or after dosage of acetaminophen. This allows for increased therapeutic dosages of acetaminophen to be administered with reduced risk of toxic effects, and for prevention of toxic effects in people with special sensitivity to acetaminophen. A composition containing both acetaminophen and grape seed proanthocyanidin extract, allowing for ease of administration of an amount of grape seed proanthocyanidin extract effective to protect from toxicity, also is disclosed. Excerpt(s): The invention relates generally to a method and composition for preventing and/or treating acetaminophen toxicity in a person who has received or is receiving an excessive amount of acetaminophen. is a well-known and reliable analgesic commonly used and available without prescription in the United States. Acetaminophen can cause serious damage to liver cells and tissues when an excessive amount is taken. The amount that can lead to this damage varies for individuals based on various factors; for example, lower body weight, past alcoholism, ingestion of acetaminophen with alcohol, or other special sensitivity all can lead to damage from ingestion of amounts of acetaminophen normally not excessive. According to the United States Poison Control
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Center, thousands of cases of acetaminophen toxicity are reported in the U.S. each year. Acetaminophen is thought to be metabolized in the liver by cytochrome P-450 enzymes, resulting in highly reactive oxygen free radicals and toxic metabolites, e.g., N-acetyl.rho.-benzoquinone imine. These metabolites interact with cellular lipids, protein, DNA, and biological macromolecules, causing cell injury and death. When acetaminophen is taken in a non-excessive amount, these metabolites are cleared by hepatic glutathione stores. Excessive amounts of acetaminophen are thought to deplete these glutathione stores, resulting in hepatic necrosis. Web site: http://www.delphion.com/details?pn=US06245336__ •
Prevention of acetaminophen overdose toxicity with organosulfur compounds Inventor(s): Yang; Chung S. (Bridgewater, NJ) Assignee(s): Rutgers University (piscataway, Nj) Patent Number: 5,474,757 Date filed: October 16, 1992 Abstract: A method of preventing acetaminophen (APAP)-induced hepatotoxicity utilizing diallyl sulfide (DAS) and diallyl sulfone (DASO.sub.2) is disclosed. DAS and DASO.sub.2 are prepared as an oral dosage form or injected. In a preferred embodiment, diallyl sulfone is added to a dosage form of acetaminophen in an amount effective to prevent the metabolism of said unit dose of acetaminophen into its hepatotoxic metabolites. In certain preferred embodiments, the above formulations further include an effective amount of N-acetylcysteine to detoxify hepatotoxic metabolites of acetaminophen. Excerpt(s): This work was supported by NIH Grant ES-03938. Acetaminophen (APAP, N-acetyl-p-aminophenol, paracetamol) is the leading analgesic and antipyretic drug used in the United States. Acetaminophen is well tolerated, lacks many of the side effects of aspirin, and is available without prescription. It is well-established that large acetaminophen overdose causes hepatotoxicity and in rare cases nephrotoxicity in humans and in experimental animals. Acute overdosage of acetaminophen results in dose-dependent and potentially fatal hepatic necrosis as well as in rare cases renal tubular necrosis and hypoglycemia. Web site: http://www.delphion.com/details?pn=US05474757__
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Process for preparing acyl aminophenols Inventor(s): Foster; James A. (Corpus Christi, TX), Mueller; Werner H. (Corpus Christi, TX), Ryan; Debra A. (Corpus Christi, TX), Wiezer; Hartmut (Eppstein/Taunus, DE) Assignee(s): Hoechst Celanese Corp. (somerville, Nj) Patent Number: 5,648,535 Date filed: May 26, 1995 Abstract: A process for the production of N-acylaminophenols by the concurrent hydrogenation of a nitrophenol to an aminophenol and the acylation of the aminophenol with acyl anhydride takes place on a continuous basis in a stirred tank reactor in which liquid product is continuously withdrawn from the reactor. Of
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particular interest is the manufacture of acetaminophen, N-acetyl-p-aminophenol by continuous reaction of p-ntirophenol, hydrogen and acetic anhydride. Excerpt(s): This invention relates to the production of N-acyl-aminophenols by hydrogenation of nitrophenols to aminophenols, and concurrently acylating the aminophenol. The invention has particular use in forming N-acetyl-p-aminophenol by hydrogenation of p-nitrophenol and concurrent acetylation of the formed paminophenol as above described in one step and on a continuous basis. The conventional process for the production of N-acetyl-p-aminophenol involves reduction of p-nitrophenol to produce p-aminophenol which is then acetylated to produce Nacetyl-p-aminophenol. The reduction of p-nitrophenol to produce p-aminophenol involves hydrogenating the p-nitrophenol in the presence of catalysts such as platinum, palladium, nickel, noble metal catalysts, or oxides of platinum, palladium, or noble metal catalysts. Gaseous hydrogen is commonly used as a reducing agent. The acetylating agent is usually acetic anhydride. The reaction medium can be acetic acid, water, a water-isopropanol mixture, or other inert medium. The above described series of reactions has been carried out simultaneously as in U.S. Pat. No. 3,076,030 and U.S. Pat. No. 3,341,587. In the process described in both of these simultaneous reaction patents, p-nitrophenol and acetic anhydride are added at the beginning of the reaction sequence, and the hydrogenation of the p-nitrophenol takes place in the presence of acetic anhydride that is in excess over the amount of p-aminophenol in the system at any given moment. The one-step synthesis of APAP is advantageous in that such process avoids the need to isolate and purify the p-aminophenol which is oxidatively unstable. Web site: http://www.delphion.com/details?pn=US05648535__ •
Process for preparing pharmaceutical compositions for use with soft gelatin formulations Inventor(s): Tindal; Stephen Charles (Lakeside, GB), Webster; Christopher Clive (Chippenham, GB), Ferdinando; Josephine Christine (Chippenham, GB), Lewis; Jacqueline Carol (Exmouth, GB) Assignee(s): R.p. Scherer Technologies, Inc. (paradise Valley, Nv) Patent Number: 6,387,400 Date filed: August 29, 2000 Abstract: The invention disclosed herein is a process for increasing the achievable concentration of a pharmaceutically active ingredient relative to fill composition viscosity for dosage units. The process is particularly useful in the preparation of soft gelatin capsules containing ibuprofen, naproxen, indomethacin, and acetaminophen, as the pharmaceutically active ingredient. As a result of the process, lesser quantities of composition ingredients other than the pharmaceutically active ingredient are needed to accomplish the same therapeutically effective dosage, thereby significantly increasing the concentration of the pharmaceutically active ingredient resulting in either a reduction in overall fill volume and dosage unit size or an increase in concentration of pharmaceutically active ingredient per dosage form. Excerpt(s): The invention disclosed herein relates to the field of oral pharmaceutical formulations. In particular, the invention relates to an improved process for preparing pharmaceutical compositions for use in soft gel formulations. The inventive process allows for a given dose of active ingredient to be placed in a smaller dosage form. Filled
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one piece soft gels have been widely known and used for many years and for a variety of purposes. Because softgels have properties which are different from conventional telescoping two-piece hardshell capsules, the soft gels are capable of retaining liquid fill material. Typically, softgels are used to contain orally consumable materials such as vitamins and pharmaceutical compositions in a liquid vehicle or carrier. In general, not all liquids are suitable as vehicles or carriers for inclusion in softgels. For example, water, propylene glycol, glycerin, low molecular weight alcohols, ketones, acids, amines and esters cannot be used as a carrier in softgels by themselves since they interact with the gel and, if present, they can only be present in relatively small amounts. Web site: http://www.delphion.com/details?pn=US06387400__ •
Processes for preparing barrier layer films for use in enzyme electrodes and films made thereby Inventor(s): Huntington; Jeffrey L. (Yellow Springs, OH), Johnson; Jay M. (Dayton, OH) Assignee(s): Ysi Incorporated (yellow Springs, Oh) Patent Number: 5,766,839 Date filed: March 19, 1996 Abstract: Methods for forming thin layer barrier layer films for use in enzyme containing laminated membranes and membranes formed thereby are disclosed. The barrier layers exhibit improved acetaminophen rejection and comprise a cellulose acetate/cellulose acetate butyrate blend. The thin layer barrier membranes are formed from a plural solvent containing solution and are cured at a critical temperature of about 102.degree.-114.degree. F., most preferably at about 106.degree. F.-114.degree. F. while traveling through a circulating hot air oven. Alternatively, the membranes can be cured at room temperature or in a stagnant oven at temperatures of from room temperature to about 175.degree. C. (350.degree. F.) for a period of from about 10 minutes to 1 hour. Excerpt(s): The invention pertains to improved methods for forming this barrier layer films that are useful as a component of an enzyme containing laminated membrane. Polarographic cell systems have met with wide acclaim particularly in the medical field, providing for detection and concentration measurement of many desired analytes. Enzymes are commonly used in such systems, especially in those situations wherein the analyte itself is not polarographically active but where a reaction product formed or reactant consumed by an enzymatic reaction with the analyte is polarographically active. The hydrogen peroxide generated by the reaction is measurable by a polarographic detector and, by appropriate calibration and calculation, glucose content in the sample can be accurately determined by the H.sub.2 O.sub.2 formed in the reaction. Web site: http://www.delphion.com/details?pn=US05766839__
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Reagents and methods for the rapid and quantitative assay of pharmacological agents Inventor(s): Cheng; Anthony K. (Anaheim, CA), Oh; Chan S. (Chino Hills, CA), Yan; Cheng F. (Irvine, CA) Assignee(s): Beckman Instruments, Inc. (fullerton, Ca) Patent Number: 5,747,352 Date filed: May 23, 1994 Abstract: Bidentate reagents for rapidly and quantitatively assaying the concentration of pharmacological agents in biological samples are described. The reagents are used in an immunoassay format for determining the concentration of desired, preselected pharmacological agents, such as benzoylecgonine, cocaine, an opiate, PCP, digoxigenin, acetaminophen, carbamazepine, phenytoin, primidone, theophylline, an aminoglycoside antibiotic, vancomycin, quinidine or a cannabinoid. Excerpt(s): The invention concerns reagents and methods for rapidly and quantitatively assaying the concentration of pharmacological agents in biological samples. More specifically, the invention concerns the formation and use of biotinylated bidentate reagents and immunoassay formats capable of determining the concentration of desired, preselected pharmacological agents, such as cocaine, acetaminophen or digoxin. The ability to assess whether an individual has been exposed to a pharmacological agent, and a capability of determining the concentration of such an agent in a biological sample is of broad importance in medicine, law enforcement and other areas. In particular, the medical and societal ramifications of substance abuse (cocaine, cannabinoids, opiates, etc.) has necessitated the development of assays capable of detecting such substances. Direct usage of cocaine has increased dramatically during the last decade (Rosenberg, N. M. et al., Amer. J. Dis. Child. 145:1430-1432 (1991)). Such usage has increased the prevalence of occult cocaine exposure in neonatals, young children and adolescents to levels approaching 5% in some urban areas of the United States (Rosenberg, N. M. et al., Amer. J. Dis. Child. 145:1430-1432 (1991)). Web site: http://www.delphion.com/details?pn=US05747352__
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Rotor granulation and coating of acetaminophen, chlorpheniramine, and, optionally dextromethorphan
pseudoephedrine,
Inventor(s): Burke; Gerald M. (North Wales, PA), Scott, III; John W. (West Chester, PA) Assignee(s): Mcneil-ppc, Inc. (milltown, Nj) Patent Number: 5,529,783 Date filed: December 19, 1994 Abstract: Chewable tablets comprising individual taste-masked coated granules comprising an analgesic and at least one water soluble medicament and methods of producing the same are described. Excerpt(s): This invention relates to chewable tablets containing more than one active medicament, maintaining good taste and mouth-feel. Orally administered medicaments are given to the patient in many forms, such as liquid solutions, emulsions, or suspensions, or in solid form such as capsules or tablets (as used herein, the term "tablet" means any shaped and compressed solid dosage form, including caplets). Medicaments administered in tablet or capsule form are usually intended to be swallowed whole. Therefore, the often disagreeable taste of the active ingredient need
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not be taken into account in formulating the dosage form, except for the provision of means to prevent the taste from being apparent during the short time that the dosage form is in the mouth. Such means may include the use of an appropriately thin and quickly dissolving coating on the tablet, the use of the gelatin capsule form, or simply compressing a tablet firmly so that it will not begin to disintegrate during the short time that it is intended to be in the mouth. It is desirable to provide the medicine either in liquid form or in a chewable solid form for children, especially toddlers, older persons, and many other persons, that have trouble swallowing whole tablets and capsules. Even where the medicine can be formulated as a liquid, it is desirable also to be able to provide a chewable solid form for convenience. Web site: http://www.delphion.com/details?pn=US05529783__
Patent Applications on Acetaminophen 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 acetaminophen: •
Acetaminophen compositions Inventor(s): Fontenette, Durwin O.; (Brandon, FL), Waranis, Robert; (Annandale, NJ) Correspondence: Donald O. Nickey; Cardinal Health, INC.; 7000 Cardinal Place; Dublin; OH; 43017; US Patent Application Number: 20030096872 Date filed: November 21, 2001 Abstract: The invention herein provides for an oral pharmaceutical composition adapted for use in capsular dosage forms comprising acetaminophen and a lactate salt alone or in combination with an acetate salt. Compositions of the invention exhibit improved solubility characteristics of the active ingredient per given fill volume, thereby permitting the use of smaller capsule sizes to deliver a given effective dose of the active ingredient. Compositions of the invention also exhibit improved clarity per concentration of active ingredient. The invention also provides for a capsular dosage form containing the composition. Excerpt(s): The present invention relates to pharmaceutical compositions comprising acetaminophen as the active ingredient. In particular, the invention pertains to acetaminophen compositions having improved solubility characteristics for encapsulation. Soft gelatin capsules or softgels are predominantly used to contain liquids wherein the active ingredients are present in the dissolved or suspended state. Filled one-piece softgels have been widely known and used for many years and for a variety of purposes. Because softgels have properties that are quite different from telescoping two-piece, hard shell capsules, the softgels are capable of retaining a liquid fill material. Softgels are often used to encapsulate consumable materials, including vitamins, dietary supplements, pharmaceuticals, and the like, in a liquid vehicle or carrier. A particularly good bioavailability of a pharmacologically active substance is attained if the active substance is successfully dissolved in a suitable solvent and the
10
This has been a common practice outside the United States prior to December 2000.
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encapsulated solution is administered to the patient. Producing highly concentrated solutions of any acidic, amphoteric or basic pharmaceutical compound is useful because it permits encapsulation in a softgel capsule of a unit dose which is small enough to permit easy swallowing. Filling a unit dose in a small softgel capsule to permit easy swallowing is useful because it increases patient acceptance of the medication. Patient acceptance of a medication is important because it is a substantial step towards solving the problem of patient noncompliance with the prescribed regimen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Analgesic and anti-inflammatory compositions containing cox-2 inhibitors Inventor(s): Cooper, Stephen Allen; (Denville, NJ) Correspondence: Darby & Darby P.C.; P.O. Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20030216461 Date filed: April 29, 2003 Abstract: The present invention is directed to an analgesic composition which consists essentially of a cyclooxygenase-2 inhibitor and a compound selected from the group consisting of non-steroidal anti-inflammatory drugs, acetaminophen and mixtures thereof. The present invention further is directed to a method for inducing analgesia through the administration of such a composition to a patient. Excerpt(s): This invention relates to a composition for alleviating pain and/or inflammation which provides both quick onset and long duration. More particularly, this invention is concerned with a composition consisting essentially of a cyclooxygenase-2 inhibitor (also referred to as a cyclooxygenase II, COX-2 or COX II inhibitor) and a second analgesic composition selected from the group consisting of NSAIDS (non-steroidal, anti-inflammatory drugs), acetaminophen and mixtures thereof. The invention is also directed to a method for alleviating pain and/or inflammation through the administration of such composition. Compounds have been found which exhibit anti-inflammatory, analgesic and antipyretic activity, (in addition to inhibiting hormone-induced uterine contractions and certain types of cancer growth) through inhibition of prostaglandin G/H synthase, also known as cyclooxygenase. Initially, only one form of cyclooxygenase was known, this corresponding to cyclooxygenase-1 or the constitutive enzyme, as originally identified in bovine seminal vesicles. This enzyme has been cloned, sequenced and characterized from various sources including sheep, mouse and man. Prostaglandins have also been found to have both physiological and pathological roles. Cyclooxygenase-1 is responsible for endogenous basal release of prostaglandins and is important in their physiological functions such as the maintenance of gastrointestinal integrity and renal blood flow. Non-steroidal anti-inflammatory drugs (NSAIDS) have been found to inhibit the cyclooxygenase-1 enzyme and thereby exhibit anti-inflammatory, analgesic and antipyretic properties. While NSAIDS exhibit excellent anti-inflammatory, analgesic and antipyretic properties and possess additional benefits such as quick onset times, NSAIDS have a potential for gastrointestinal toxicity, and/or renal side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Analgesics combined with naturally-occurring chondroprotective agents Inventor(s): Hammerly, Milton; (Parker, CO) Correspondence: Chistopher J. Whewell; Western Patent Group; 6020 Tonkowa Trail; Georgetown; TX; 78628; US Patent Application Number: 20010046971 Date filed: February 15, 2001 Abstract: Provided herein are medicinal compositions of matter that comprise a chondroprotective component and an analgesic component, wherein the chondroprotective component is naturally occurring in a preferred form of the invention, and the analgesic component is acetaminophen or its derivatives or analogs. The invention also provides procedures for administering the compositions to a patient who is afflicted with osteoarthritis. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/183,704 filed Feb. 18, 2000, the entire contents of which are herein incorporated by reference. This invention relates to medicinal compositions of matter comprising an analgesic in combination with a naturally-occurring chondro-protective agent. The compositions according to the invention are suitable for oral administration. Alternatively, the combinations of the invention may be administered by any conventional means of drug administration. Osteoarthritis ("OA") is the most common form of joint disease in the United States. It represents a major concern for health care providers because of its marked impact on the quality of life of those afflicted by it. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Coated conditioners for use in foods and pharmaceuticals Inventor(s): Cornelius, John Mark; (Forest Hill, MD), Freeman, Gary M.; (Macon, GA), Neades, June M.; (Havre de Grace, MD), Tarquini, Michael E.; (Havre de Grace, MD) Correspondence: David Mitchell Goodrich, ESQ.; J. M. Huber Corporation; 333 Thornall Street; Edison; NJ; 08837-2220; US Patent Application Number: 20030203019 Date filed: April 30, 2002 Abstract: An edible composition comprising a coated conditioner that contains a hydrophobization agent and inorganic particles is provided. When incorporated into an edible composition (such as a powdered pharmaceutical or food product), the coated conditioners inhibit caking and promote the free flow of powder. Suitable hydrophobization agents include food-grade fatty acids, food-grade oils, food-grade waxes, and food-grade gums, while suitable inorganic particles are selected from the group consisting of silica, silicates, calcium carbonates, phosphates, and clays. The coated conditioner is particularly suitable for use in pharmaceutical preparations, such as acetaminophen. Excerpt(s): For the last several years materials such as silica, sodium aluminosilicates, kaolin clays, tricalcium phosphate, and calcium silicates have been used as "conditioners" in dry and powdered foods to prevent caking and encourage the free flow of powdered food particles. In pharmaceuticals, fumed silica has been widely used as an excipient (conditioner or glidant) for the same reasons. These conditioners absorb moisture from the atmosphere or package to prevent the food particles from sticking
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together in moisture or pressure cakes and also act as "ball bearings" to coat the surface of the food particles, thus preventing agglomeration among adjacent particles. These conditioners, also known as free flow, and anticaking agents are permitted for use at levels less than or equal to 2.0 wt % in the final food product by the U.S. Food and Drug Administration. Additionally these conditioners may also be used in other applications such as fertilizers, pesticides, and polymers. While these conditioners are used in many commercially-prepared food powders susceptible to pressure or moisture caking, they lack efficacy for use in many pharmaceuticals, as well as certain food products that are hygroscopic, contain high concentrations of proteinaceous material, or have a high content of fats and oils such as garlic powder, de-lactosed milk powder or hydrolyzed vegetable powder. In fact, for many foods and pharmaceuticals a suitable conditioner is not available. Certain materials, such as the J. M. Huber Corporation's Zeosyl.RTM. T 166 (a silica treated with a siloxane to render the silica hydrophobic) can significantly inhibit caking in foods and pharmaceuticals. However, silane-treated silicas are only permitted in food applications as defoaming agents for beet and cane sugar. They are not permitted for use as food conditioners. Thus for many pharmaceuticals and food products there is no approved commercially-available conditioner that provides excellent anti-caking performance. For example, the common pain reliever acetaminophen (N-acetyl-para-aminophenol) has a tightly packed crystalline form that often results in the formation of pressure and moisture cakes of the powder during storage, leading to poor flow performance. Commercially-available fumed silicas, such as Cab-O-Sil.RTM. M5 from the Cabot Corporation, Bellrica, Mass., provide some improvement in flow performance, but they do not completely address the problem. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination therapy for the treatment of migraine Inventor(s): Saper, Joel; (Ann Arbor, MI) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020099059 Date filed: August 21, 2001 Abstract: A method of treating migraine and compositions useful therein are disclosed. The compositions comprise a selective 5-hydroxytriptamine receptor agonist and acetaminophen, non-steroidal anti-inflammatory agents and/or caffeine. Excerpt(s): This non-provisional application claims priority from provisional application U.S. Ser. No. 60/227,350 filed Aug. 23, 2000. The present invention relates to compositions and methods for alleviating the symptoms and pain associated with acute migraine attack. More particularly, the invention relates to the use of acetaminophen (APAP), a nonsteroid antiinflammatory agent (NSAID) and/or caffeine (CAF), with a selective hydroxytriptamine.sub.1 receptor subtype agonist or a selective 5hydroxytriyptamine 1B/1D (5-HT 1B/1D) receptor agonist for alleviating the symptoms and pain associated with migraine. An estimated 23-25 million Americans--about 18% of women and 6% of men--suffer from migraine pain and migraine-related symptoms. Attacks are common, with more than 50% of sufferers experiencing one or more episodes per month. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Composition and method for treating the effects of diseases and maladies Inventor(s): Gelber, Daniel; (Woodland Hills, CA), Kleinberger, Richard; (Sherman Oaks, CA) Correspondence: Terry W. Kramer; Kramer & Associates; 2001 JEFF. Davis HWY. Suite 1101; Arlington; VA; 22202; US Patent Application Number: 20020006445 Date filed: January 5, 2001 Abstract: A medicinal composition for treating pain resulting from an inflammatory response comprises at least one pain relieving and anti-inflammatory pharmaceutical and at least one nutraceutical in a pharmaceutically acceptable base. The pharmaceutical is preferably acetaminophen or a non-steroidal anti-inflammatory drug (NSAID). The nutraceutical is preferably an immune booster, an anti-oxidant, a liver protectant, or a joint relief agent. Methods of using these compositions to treat pain caused by inflammation are also disclosed. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/184,351 entitled "Composition and Method For Treating The Effects of A Cold or Flu," filed on Feb. 23, 2000. The present invention relates to the field of medicinal compositions and methods of using said compositions for treating diseases and maladies. In particular, the present invention relates to formulations comprising combinations of a pharmaceutical in combination with a nutraceutical, which when administered to a person in need thereof have the effect of increasing the beneficial effects of the pharmaceutical utilized. Beginning in prehistoric times, humans have attempted to treat every known type of illness and malady with naturally occurring products. Such products were initially in their natural state, such as leaves, berries, roots, tree cuttings and extracts. With the advance of science, and greater understanding of chemistry, humans have been able to synthetically produce and extract a great variety of pharmaceuticals which were previously unknown or unidentified. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions of chromene cyclooxygenase-2 selective inhibitors and acetaminophen for treatment and prevention of inflammation, inflammation-mediated disorders and pain Inventor(s): Seibert, Karen; (St. Louis, MO) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20030114483 Date filed: September 18, 2002 Abstract: A composition is provided comprising a chromene cyclooxygenase-2 selective inhibitor and acetaminophen. The composition is effective for the treatment and prevention of inflammation, an inflammation-mediated disorder, and pain. Excerpt(s): This application claims priority from Provisional Application Serial No. 60/322,995 filed on Sep. 18, 2001, which is hereby incorporated by reference in its entirety. The present invention provides a composition for the treatment and prevention of inflammation, inflammation-mediated disorders and pain. More particularly, the invention is directed toward a composition of a chromene cyclooxygenase-2 selective
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inhibitor and acetaminophen that is effective in the treatment and prevention of inflammation, inflammation-mediated disorders and pain. Inflammatory disease is any disease marked by inflammation, which is a localized protective response elicited by injury or destruction of tissues and serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. The classical signs of pain, heat, redness, swelling and loss of function characterize inflammation in the acute form. Inflammation occurs when, upon injury, recruited polymorphonuclear leukocytes release reactive oxygen species (ROS) in oxidative bursts resulting in a complex cascade of events. Histologically, it involves a complex series of events, including dilation of arterioles, capillaries, and venules, with increased permeability and blood flow; exudation of fluids, including plasma proteins; and leukocytic migration into the inflammatory focus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Delivery of analgesics through an inhalation route Inventor(s): Rabinowitz, Joshua D.; (Mountain View, CA), Zaffaroni, Alejandro C.; (Atherton, CA) Correspondence: Richard R. Eckman; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030017117 Date filed: May 16, 2002 Abstract: The present invention relates to the delivery of analgesics through an inhalation route. Specifically, it relates to aerosols containing acetaminophen, orphenadrine or tramadol that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of acetaminophen, orphenadrine or tramadol. In a method aspect of the present invention, one of acetaminophen, orphenadrine or tramadol is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of acetaminophen, orphenadrine or tramadol, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering acetaminophen, orphenadrine or tramadol through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of acetaminophen, orphenadrine or tramadol; and, b) a device that forms an acetaminophen, orphenadrine or tramadol containing aerosol from the composition, for inhalation by the mammal. Excerpt(s): This application claims priority to U.S. provisional application Serial No. 60/294,203 entitled "Thermal Vapor Delivery of Drugs," filed May 24, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. This application further claims priority to U.S. provisional application Serial No. 60/317,479 entitled "Aerosol Drug Delivery," filed Sep. 5, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. The present invention relates to the delivery of analgesics through an inhalation route. Specifically, it relates to aerosols containing acetaminophen, orphenadrine or tramadol that are used in inhalation therapy. There are a number of compositions currently marketed as analgesics. The compositions contain at least one active ingredient that provides for the observed therapeutic effects. Among the active ingredients given in analgesic compositions are acetaminophen, orphenadrine and tramadol.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Directly compressible acetaminophen compositions Inventor(s): Camarco, Wayne; (Hoboken, NJ), Upadhyay, Ajay Hasmukhlal; (Sayreville, NJ) Correspondence: Kevin E. MC Veigh; Rhodia INC.; 259 Prospect Plains Road; Cranbury; NJ; 08512; US Patent Application Number: 20010044472 Date filed: March 14, 2001 Abstract: Acetaminophen compositions are disclosed which are capable of being directly compressed, without addition of other components, into an tablet dosage form, and which include, based on the total weight of the dry components of the composition, from about 80 percent by weight to about 98 percent by weight acetaminophen, a fluidizing agent, a binder compound, a starch, a disintegrant and a lubricant. Excerpt(s): This invention relates to directly compressible acetaminophen (N-acetyl-paminophenol or APAP) compositions and to a process for preparing such compositions. The invention also relates to the preparation of tablets from such compositions. The invention also includes such acetaminophen granulations alone or combined with other co-active ingredients present in low quantity. Generally there are four methods in use in the United States for manufacture of tablets, namely direct compression, dry powder blend, pre-compressed dry powder blend and wet granulation, as explained in U.S. Pat. No. 4,439,453. In the direct compression method, all the required tabletting ingredients (active and aids) are incorporated into a free flowing granulation which is supplied to the manufacturer of bulk tablets. The granulation requires no pre-processing or blending with additional aids in order to be tabletted. Rather, the free flowing granulation supplied to the tablet manufacturer can be charged directly to a tabletting press. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Directly compressible high load acetaminophen formulations Inventor(s): Hunter, Edward A.; (Glenham, NY), Sherwood, Bob E.; (Amenia, NY), Zeleznik, Joseph A.; (New Paltz, NY) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20010014353 Date filed: March 2, 2001 Abstract: Direct compressed solid pharmaceutical dosage forms containing:a) from about 40 to about 95% by weight acetaminophen;b) from about 1 to about 60% by weight of a direct compression vehicle comprising microcrystalline cellulose; andc) from about 0.01 to about 4.0% by weight of a pharmaceutically-acceptabl- e lubricantare disclosed. The acetaminophen and direct compression vehicle are combined under high shear conditions which are sufficient to transform acetaminophen and direct compression vehicle into a homogenous granulate without degradation. In preferred aspects of the invention, the lubricant is also combined with the acetaminophen and
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direct compression vehicle under high shear conditions. Methods of preparing the directly compressed solid pharmaceutical dosage forms and methods of treatment with the dosage forms are also disclosed. The methods are particularly well suited for preparing directly compressed dosage forms containing high load (i.e., up to 80% or greater) amounts of acetaminophen based on the weight of the total tablet. Excerpt(s): The present invention relates to methods of preparing solid dosage forms using direct compression techniques. In particular, the present invention relates to methods of directly compressing tablets containing relatively high amounts of acetaminophen based on the total tablet weight. In order to prepare a solid dosage form containing one or more active ingredients (such as drugs), it is necessary for the materials to be compressed into the dosage form possess certain physical characteristics which lend themselves to solid dosage form processing. Among other things, the material to be compressed must be free-flowing, must be lubricated, and, importantly, must possess sufficient cohesiveness to insure that the solid dosage form remains intact after compression. In the case of tablets, the tablet is formed by pressure being applied to the material to be tableted on a tablet press. A tablet press includes a lower punch which fits into a die from the bottom and a upper punch having a corresponding shape and dimension which enters the die cavity from the top after the tabletting material fills the die cavity. The tablet is formed by pressure applied on the lower and upper punches. The ability of the material to flow freely into the die is important in order to insure that there is a uniform filling of the die and a continuous movement of the material from the source of the material, e.g. a feeder hopper. The lubricity of the material is crucial in the preparation of the solid dosage forms since the compressed material must be readily ejected from the punch faces. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Migraine medicine and method of treating the same without caffeine Inventor(s): Imanzahrai, Ashkan; (San Jose, CA) Correspondence: Kevin D. Mccarthy, ESQ.; Hodgson Russ Llp; Suite 2000; One M&t Plaza; Buffalo; NY; 14203-2391; US Patent Application Number: 20020091162 Date filed: January 4, 2002 Abstract: This invention is a safe and effective composition and method for treating acute migraine attacks using pseudoephedrine, acetaminophen, and other agents in an orally administrated form to alleviate the pain and cluster of symptoms characteristic of migraine attacks such as nausea, photophobia, phonophobia, and functional disabilities as well as the prodrome phase of a migraine attack. Excerpt(s): This application claims priority as a divisional application of U.S. nonprovisional patent application serial no. 09/593,238 (filed on Jun. 14, 2000) which relies on the priority of provisional patent application Serial Number 60/144,973 which was filed on Jul. 22, 1999. The present invention relates generally to compositions and methods used to alleviate the symptoms and pain associated with an acute migraine attack. Many migraine sufferers use single-agent nonprescription analgesics such as acetaminophen, or aspirin, or non-steroidal anti-inflammatory agents to treat their attacks. (Lipton R B, Newman L C, Solomon S. Over-the-counter medication and the treatment of migraine. Headache 1994; 34:547-548.) In other countries, a number of nonprescription drugs are specifically approved for migraine pain. (Lipton R B,
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Newman L C, Solomon S. Over-the-counter medication and the treatment of migraine. Headache 1994; 34:547-548.) The effectiveness of self-treatment of a migraine and the effectiveness of most such nonprescription drugs in relieving or aborting migraine pain and/or the characteristic symptoms of a migraine has not been adequately studied in well-controlled clinical trials. (Lipton R B, Newman L C, Solomon S. Over-the-counter medication and the treatment of migraine. Headache 1994; 34:547-548.) Acetaminophen, aspirin, and caffeine are approved for relief of nonspecific headaches and tension headaches (Migliardi J R, Armellino J J, Friedman M, Gillings D B, Beaver W T. Caffeine as an analgesic adjuvant in tension headache. Clin Pharmacol Ther 1994; 56:576-586), which are clinical and physiologically distinct from a migraine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Opioid agonist/opioid antagonist/acetaminophen combinations Inventor(s): Colucci, Robert D.; (Newtown, CT), Kaiko, Robert F.; (Weston, CT) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20020058673 Date filed: November 5, 2001 Abstract: The invention is directed in part to oral dosage forms comprising a combination of an opioid agonist, acetaminophen and an orally active opioid antagonist, the opioid antagonist being included in a ratio to the opioid agonist to provide a combination product which is analgesically effective when the combination is administered orally, but which is aversive in a physically dependent subject. Preferably, the amount of opioid antagonist included in the combination product provides at least a mildly negative, "aversive" experience in physically dependent addicts (e.g., precipitated abstinence syndrome). Excerpt(s): This application is a continuation-in-part application of U.S. Ser. No. 09/218,662, which is in turn a continuation application of U.S. Provisional Application Serial No. 60/068,480 filed Dec. 22, 1997, hereby incorporated by reference. Opioids, also known as opioid agonists, are a group of drugs that exhibit opium or morphine-like properties. The opioids are employed primarily as moderate to strong analgesics, but have many other pharmacological effects as well, including drowsiness, respiratory depression, changes in mood and mental clouding without a resulting loss of consciousness. Opioids act as agonists, interacting with stereospecific and saturable binding sites in the brain and other tissues. Endogenous opioid-like peptides are present particularly in areas of the central nervous system that are presumed to be related to the perception of pain; to movement, mood and behavior, and to the regulation of neuroendocrinological functions. Opium contains more than twenty distinct alkaloids. Morphine, codeine and papaverine are included in this group. By the middle of the nineteenth century, the use of pure alkaloids such as morphine rather than crude opium preparations began to spread throughout the medical world. Parenteral use of morphine tended to produce a more severe variety of compulsive drug use. The problem of (addiction to opioids stimulated a search for potent analgesics that would be free of the potential to produce addiction. By 1967, researchers had concluded that the complex interactions among morphine-like drugs, antagonists, and what was then called "mixed agonist-antagonist" could best be explained by postulating the existence of more than one type of receptor for opioids and related drugs. With the advent of new totally synthetic entities with morphine-like actions, the term "opioid" was generally retained
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as a generic designation for all exogenous substances that bind stereo-specifically to any of several subspecies of opioid receptors and produce agonist actions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Oxidase-base sensors for selective analysis of analytes in aqueous samples Inventor(s): Lu, Fang; (Millbrae, CA), Lu, Frank N. W.; (San Mateo, CA), Wang, Kai Hua; (San Bruno, CA) Correspondence: John H. Faro, ESQ.; Faro & Associates; P.O. Box 4904; Key Biscayne; FL; 33149-4904; US Patent Application Number: 20030236448 Date filed: March 27, 2001 Abstract: A system and method for the selective electrochemical analysis of an aqueous test sample for an analyte of interest, with biosensor comprising a working electrode comprising (a) an effective amount of oxidase enzyme specific for the analyte of interest, and (b) a metal catalysts doped carbon composition specific for the catalytic reduction of hydrogen peroxide liberated from enzymatic action of said oxidase upon the analyte of interest. The system and method of this invention effectively perform such selective electrochemical analysis in the presence of common interferents (e.g. acetaminophen, uric and ascorbic acids, catecholamines) at relative low voltages (from about +0.3 to 0.25V), so as to avoid generation of an overlapping signal from such interferents. Excerpt(s): This invention relates to a method and to a device for the selective analysis of analytes in an aqueous sample by electrochemical means. More specifically, this invention is directed to test device for the selective amperometric measurement of hydrogen peroxide as indicative of the presence and concentration of an analyte of interest in an aqueous sample. The use of so-called "biosensors" to directly detect the presence and concentration of an analyte of interest by amperometric and/or potentiometric measurement is well-known. The various electrochemical mechanisms that lend themselves to such direct detection techniques are also well-known. In brief, such techniques involve contacting a sample with a reagent (e.g. enzyme), under analytical conditions, to effect the release or formation of a compound that is electrochemically active, or can be converted to a compound or species that is electrochemically active. The electrochemically active compound has a characteristic signal that is manifest as a change in voltage and/or current can then be monitored, and the recorded signal correlated/compared with a standard response curve for determination of the presence and, possibly, the concentration of the analyte of interest. One of the model systems typically used to exemplify such electrochemical analysis, comprises the quantitative determination of glucose in a biological sample. As is fully appreciated, the precision determination of quantitative glucose levels in biological fluid samples is critical to control of diabetes in both insulin dependent (Type I) diabetics and diabetics that are capable of control of their blood sugar by rigorous adherence to diet, Type II diabetics. The biological fluid specimen typically used in such analysis of glucose by such individuals can include venous blood, capillary blood or interstitial fluid. The biochemical reaction used to determine the amount of glucose in the sample typically involves either an a spectrophotometric method or an electrochemical method. Electrochemical analysis has been widely used in detection of glucose in biological sample because of its accuracy, convenience and cost over the spectrophotometric method.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of pain Inventor(s): Camborde, Francoise; (Orsay, FR), Cloarec, Alix; (Triel Sur Seine, FR), Conway, Charles; (Cheshire, CT) Correspondence: Marla J Mathias; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20010016584 Date filed: January 4, 2001 Abstract: A method of treating pain with acetaminophen comprises the concurrent administration of buspirone. This combination of agents surprisingly results in a morphine-like analgesic response characterized by rapid onset, greater pain relief, and a longer duration of action. Excerpt(s): This continuation-in-part application claims priority from PCT/FR00/01817 filed Jun. 29, 2000 which claims priority from French patent application 99.08363 filed Jun. 30, 1999. This invention relates to the use of a therapeutic combination of two compounds to treat pain. The method of pain treatment comprises co-administration of buspirone with acetaminophen (paracetamol). This combination of agents produces a more robust opioid-type analgesia providing more rapid onset and longer duration. Acetaminophen is an established analgesic agent having only weak anti-inflammatory activity and can be classified as a non-NSAID analgesic. Ibuprofen is an example of a non-steroidal analgesic having significant anti-inflammatory properties and is classified as a non-steroidal anti-inflammatory drug (NSAID). Acetaminophen is believed to relieve pain by elevation of the pain threshold and is generally given in amounts ranging from about 600 to 1300 mg per dose in humans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of acetaminophen to prevent and treat arteriosclerosis Inventor(s): Nelson, Edward B.; (Lower Gwynedd, PA), Smith, Charles V.; (Blacklick, OH), Taylor, Addison A.; (Houston, TX) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20020132855 Date filed: June 22, 2001 Abstract: This invention relates to a method of treating, preventing, and regressing arteriosclerosis including atherosclerosis in mammals by administering an effective amount of acetaminophen or pharmaceutically acceptable salt thereof and optionally a second active ingredient, along with compositions containing the same. Excerpt(s): This Application claims the benefit of U.S. application Ser. No. 60/222,781 filed on Aug. 3, 2000, which is incorporated by reference in its entirety herein. This invention relates to a method for preventing, treating, and regressing arteriosclerosis, and in particular atherosclerosis, via the administration of an effective amount of acetaminophen. Arteriosclerosis is understood to be a pathologic condition of thickening and loss of elasticity of arterial walls. See Dorland's Illustrated Medical
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Dictionary, p. 143 (25.sup.th Ed. 1974). One form of arteriosclerosis is atherosclerosis, which is understood to be a pathologic condition of degeneration and hardening of the walls of arteries and sometimes the valves of the heart. Atherosclerosis is also associated with an accumulation of fatty lipid oxidation products in the walls of such blood vessels. See Dorland's Pocket Medical Dictionary, p. 74 (21.sup.st Ed. 1968). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals Inventor(s): Corson, Barbara E.; (Fawn Grove, PA), Hammad, Tarek; (Baltimore, MD), Henderson, Robert W.; (Baldwin, MD), Henderson, Todd R.; (Jarrettsville, MD), Lippiello, Louis; (Forest Hill, MD), Soliman, Medhat; (Minya, EG) Correspondence: Covington & Burling; 1201 Pennsylvania Avenue, NW; Washington; DC; 20004-2401; US Patent Application Number: 20030129261 Date filed: July 11, 2002 Abstract: The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans and animals comprising any or all of anabolic, anti-catabolic, anti-oxidant and analgesic agents, including aminosugars, Sadenosylmethionine, arachadonic acid, GAGs, including pentosan, collagen type II, tetracyclines or tetracycline-like compounds, diacerin, super oxide dismutase, Lergothionine, one or more avocado/soybean unsaponifiables, and an analgesic, e.g., acetaminophen, and to methods of treating humans and animals by administration of these novel compositions to humans and animals in need thereof. Excerpt(s): In connection with this application, priority is claimed to the following provisional application, A COMPOSITION OF ACETAMINOPHEN, AN AMINOSUGAR AND A GLYCOSAMINOGLYCAN, U.S. Serial No. 60/088,205, filed Jun. 5, 1998. The present application is also a continuation-in-part application of U.S. patent application Ser. No. 09/249,335, filed Feb. 12, 1999, the disclosure of which is hereby incorporated by reference herein in its entirety. That application claimed priority to provisional application: THE USE OF ANABOLIC AGENTS, ANTI-CATABOLIC AGENTS, ANTIOXIDANT AGENTS, AND ANALGESICS FOR PROTECTION, TREATMENT AND REPAIR OF CONNECTIVE TISSUES IN HUMANS AND ANIMALS, U.S. Serial No. 60/074,594, filed Feb. 13, 1998. The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans and other animals. The tissues of mammals, including humans, are in a constant state of flux between the anabolic processes that build up tissues, and the catabolic processes which degrade tissues. The state of health exists when there is a balance between these two processes, and derangements of the balance produce disease. This holds true for all tissues of the body. Connective tissues are of particular importance for several reasons. First, they support the "functional cells" of the body, i.e., epithelial, muscle and neural cells. Second, they play critical roles in intercellular communication, which is essential for multicellular life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with acetaminophen, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “acetaminophen” (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 acetaminophen. You can also use this procedure to view pending patent applications concerning acetaminophen. 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 7. BOOKS ON ACETAMINOPHEN Overview This chapter provides bibliographic book references relating to acetaminophen. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on acetaminophen 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 “acetaminophen” (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 acetaminophen: •
AAKP Patient Plan. Phase Four: Ongoing Treatment Source: Tampa, FL: American Association of Kidney Patients. 2001. 54 p. Contact: Available from American Association of Kidney Patients (AAKP). 100 South Ashley Drive, Suite 280, Tampa, FL 33602. (800) 749-AAKP or (813) 223-7099. E-mail:
[email protected]. Website: www.aakp.org. PRICE: Single copy free. Summary: This booklet is the final entry in a four phase series of instructional materials for kidney patients. Published by the American Association of Kidney Patients (AAKP), the booklets are designed to address questions and concerns at various phases of the disease process. The four phases covered are diagnosis and treatment options, access and initiation, stabilization, and ongoing treatment. During each of these phases, the patient can keep control of his or her life by staying active and learning as much as possible about kidney disease and treatment. This fourth booklet focuses on strategies to
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maintain good health during ongoing treatment for kidney disease. Topics covered include the long term health care team; long term health issues, including anemia, bone disease, parathyroid glands, muscle cramps, hypertension, neuropathy, dialysis associated amyloidosis, skin problems, and depression and anxiety; transplant health issues, including chronic rejection, heart disease, women's issues, cholesterol levels, diabetes, and cancer; normal aging considerations for dialysis and transplant patients; medications, including acetaminophen, aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), cough medicines, calcium carbonate, H2 blockers, antihistamine, and herbs; family issues, including communication; and financial issues. The booklet concludes with a glossary of terms and an appendix that lists information resources (including web sites), ESRD networks, questions to ask the health care team, and forms to record important medical information. The booklet encourages readers to educate themselves and become active members of their own health care team. There are quotes and suggestions from other kidney patients sprinkled throughout the text. The booklet is illustrated with black and white photographs. •
Handbook of Liver Disease Source: Philadelphia, PA: Churchill-Livingstone. 1998. 534 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. Email:
[email protected]. PRICE: $73.00 plus shipping and handling. ISBN: 0443055203. Summary: This comprehensive handbook in outline format offers easy access to information on the full range of liver disorders, and covers symptoms, signs, differential diagnoses, and treatments. A total of 34 chapters cover the following topics: assessment of liver function and diagnostic studies, acute liver failure, chronic viral hepatitis, acute viral hepatitis, autoimmune hepatitis, alcoholic liver disease, fatty liver and nonalcoholic steatohepatitis, drug induced and toxic liver disease, cirrhosis and portal hypertension, portal hypertension and gastrointestinal bleeding, ascites and spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson's disease and related disorders, alpha 1 antitrypsin deficiency and other metabolic liver diseases, Budd Chiari syndrome and other vascular disorders, the liver in heart failure, the liver in pregnancy, the liver in systemic disease, pediatric liver disease, liver disease in the elderly, HIV and the liver, granulomatous liver disease, hepatic tumors, hepatic abscesses and cysts, other infections involving the liver, surgery in the patient with liver disease and postoperative jaundice, liver transplantation, cholelithiasis and cholecystitis, diseases of the bile ducts, and tumors of the biliary tract. The book features lists that summarize key information and numerous figures and tables on topics such as acetaminophen toxicity, classifications of chronic hepatitis, and indications for liver transplantation. Each chapter was written by an acknowledged expert in the field and includes references for additional study. A subject index concludes the volume.
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Diagnosis and Nonsurgical Management of Osteoarthritis, Second Edition Source: Caddo, OK: Professional Communications, Inc. 2000. 304 p. Contact: Available from Professional Communications, Inc. P.O. Box 10, Caddo, OK 74729. (800) 337-9838. Fax (580) 367-9989. PRICE: $24.95 plus shipping and handling. ISBN 1884735576.
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Summary: This monograph provides health professionals with information on the diagnosis and nonsurgical management of osteoarthritis (OA). Part 1 presents general information about OA, including its definition, epidemiology (prevalence and risk factors), pathology, and pathogenesis. Part 2 deals with diagnosis, focusing on the clinical features of OA; the origins of joint pain; the pitfalls in diagnosing OA such as misinterpreting pain, the deformity, the radiographs, and the laboratory results; synovial fluid analysis; and the radiographic features of OA. Part 3 examines nonmedicinal therapy for OA pain, including aerobic exercise, range of motion and strengthening exercises, joint protection, weight loss, thermal modalities, patellar taping, tidal irrigation of the knee, use of wedged insoles, and patient education. Part 4 discusses the efficacy and adverse effects of systemic pharmacologic therapy, focusing on acetaminophen and nonspecific nonsteroidal antiinflammatory drugs (NSAIDs), NSAIDs that are specific inhibitors of cyclooxygenase-2, and opioids. Part 5 explores local therapies, including rubefacients and capsaicin cream, intraarticular injection of corticosteroids, and intraarticular injection of hyaluronic acid. Part 6 presents a rational strategy for treating OA pain. Part 7 highlights other therapies, including disease modifying drugs such as NSAIDs, heparinoids, tetracyclines, diacerhein, and glucosamine sulfate, as well as surgical intervention. 34 figures, 39 tables, 23 color plates, and numerous references. •
Liver Disorders Sourcebook Source: Detroit, MI: Omnigraphics. 2000. 591 p. Contact: Available from Omnigraphics, Inc. 615 Griswold, Detroit, MI 48226. (800) 2341340. Fax (800) 875-1340. PRICE: $78.00 plus shipping and handling. ISBN: 0780802403. Summary: This Sourcebook provides basic health care information about liver functions, guidelines for liver health, and tests that assess liver distress. The book also presents the symptoms, treatments, and preventive measures available for liver cancer; hepatitis A, B, C, D and E; genetically based liver diseases; and other liver diseases. The liver transplantation process is explained. Specific topics include strategies for protecting the liver, risk factors, common laboratory tests in liver disease, liver biopsy, cancer tumor markers, cirrhosis (scarring of the liver), infectious agents and parasites, pregnancy and the liver, jaundice in the healthy newborn, the liver's response to drugs, alcohol and the liver, acetaminophen, herbs and alternative medicine, galactosemia, Gaucher disease, hereditary hemochromatosis, Niemann-Pick disease, Wilson's disease, biliary atresia, cystic disease of the liver, fatty liver, gallstones, primary biliary cirrhosis, primary sclerosing cholangitis, organ donation, and the bioartificial liver. A glossary, a directory of organizations and support groups with up to date contact information (including websites and email addresses), a listing of transplant centers, and a subject index conclude the volume.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “acetaminophen” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “acetaminophen” (or a synonym) in
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their titles. The following is indicative of the results you might find when searching for “acetaminophen” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Acetaminophen: Index of New Information by American Health Research Inst; ISBN: 0788301586; http://www.amazon.com/exec/obidos/ASIN/0788301586/icongroupinterna
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Acetaminophen-codeine : how to take your medicine (SuDoc HE 20.4010/a:Ac 3) by Judy Folkenberg; ISBN: B0001077DC; http://www.amazon.com/exec/obidos/ASIN/B0001077DC/icongroupinterna
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The 2000-2005 Outlook for Acetaminophen (Paracetamol) in the Middle East by Inc. Icon Group International (Editor); ISBN: 0757673880; http://www.amazon.com/exec/obidos/ASIN/0757673880/icongroupinterna
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The 2000-2005 World Outlook for Acetaminophen (paracetamol) by The Research Group, et al; ISBN: 0757650937; http://www.amazon.com/exec/obidos/ASIN/0757650937/icongroupinterna
Chapters on Acetaminophen In order to find chapters that specifically relate to acetaminophen, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and acetaminophen 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 “acetaminophen” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on acetaminophen: •
Liver Disease Caused by Drugs, Anesthetics, and Toxins Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1403-1447. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Hepatotoxicity is liver injury caused by drugs and other chemicals. Adverse drug reactions are noxious, unintentional effects that occur at doses used for prophylaxis and therapy. This chapter on liver disease caused by drugs, anesthetics, and toxins is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include definitions and the general importance of drugs and toxins as causes of liver disease; epidemiology, including individual risk factors; pathophysiology; the clinicopathologic features of drug-induced liver disease, including classification and histopathology; prevention and management; dose-dependent hepatotoxicity, including that due to acetaminophen and niacin (nicotinic acid); drug-induced acute hepatitis; drug-induced granulomatous hepatitis; drug-induced chronic hepatitis; drug-induced cholestasis; chronic cholestasis; liver disease caused by anesthetic agents and jaundice in the postoperative period; drug-
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induced steatohepatitis, hepatic fibrosis, and cirrhosis; vascular toxicity; liver tumors; and complementary and alternative medicines and environmental agents. The chapter includes a mini-outline with page citations, full-color illustrations, and extensive references. 1 figure. 12 tables. 437 references. •
Drugs and the Liver Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.335-363. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: The liver is particularly concerned with drug metabolism, and especially of drugs given orally. Drugs can cause toxic effects that can mimic almost every naturally occurring liver disease in man. This chapter on drugs and the liver is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter is organized into specific pathologies and their potential causes: hepato-cellular zone 3 necrosis, due to carbon tetrachloride, Amanita mushrooms, paracetamol (acetaminophen), salicylates, hyperthermia, hypothermia, and burns; hepato-cellular zone 1 necrosis, due to ferrous sulfate or phosphorus; mitochondrial cytopathies, due to sodium valproate, tetracyclines, tacrine, antiviral nucleoside analogues, and Bacillus cereus; steatohepatitis, due to perhexiline maleate, amiodarone, synthetic estrogens, and calcium channel blockers; fibrosis, due to methotrexate, other cytotoxic drugs, arsenic, vinyl chloride, vitamin A, and retinoids; vascular changes, due to sinusoidal dilatation, peliosis hepatitis, and veno-occlusive disease (VOD); acute hepatitis, due to isoniazid, methyl dopa, halothane, hydrofluorocarbons, systemic antifungals, oncology drugs, nervous system modifiers, sustained-release nicotinic acid (niacin), sulfonamides and derivatives, nonsteroidal anti-inflammatory drugs, antithyroid drugs, quinidine and quinine, troglitazone, and anti-convulsants; chronic hepatitis, due to herbal remedies and recreational drugs; canalicular cholestasis, due to cyclosporine A and ciprofloxacin; hepato-canalicular cholestasis, due to chlorpromazine, penicillins, sulfonamides, erythromycin, haloperidol, cimetidine and ranitidine, oral hypoglycemic agents, tamoxifen, other causes, and dextropropoxyphene; ductular cholestasis; biliary sludge; sclerosing cholangitis; hepatic nodules and tumors; and hepatocellular carcinoma (HCC, liver cancer). 28 figures. 5 tables. 170 references.
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Acute Liver Failure Source: in Friedman, L.S. and Keeffe, E.B., eds. Handbook of Liver Disease. Philadelphia, PA: Churchill-Livingstone. 1998. p. 15-26. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. Email:
[email protected]. PRICE: $73.00 plus shipping and handling. ISBN: 0443055203. Summary: This chapter on acute liver failure is from a comprehensive handbook in outline format that offers easy access to information on the full range of liver disorders and covers symptoms, signs, differential diagnoses, and treatments. The authors define acute liver failure as a syndrome of rapidly evolving hepatic synthetic dysfunction that is complicated by coagulopathy and, in advanced stages, hepatic encephalopathy. Acute liver failure can be divided into two subgroups: fulminant hepatic failure, with hepatic
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encephalopathy developing within 8 weeks of the onset of illness (or at least 2 weeks after the onset of jaundice); and subfulminant hepatic failure, with hepatic encephalopathy developing 8 weeks to 6 months after the onset of illness (or 2 weeks to 3 months after the onset of jaundice). Fuliminant hepatic failure is most often caused by acute hepatitis A, acute hepatitis B, or acetaminophen overdose, while subfulminant hepatic failure is more often caused by drug induced hepatotoxicity or unknown factors. The major complications of acute liver failure that require preventive measures or specific therapy include cerebral edema, coagulopathy, renal failure, hypoglycemia, and infection. Management of acute liver failure is directed toward aggressive supportive care in an intensive care unit and determination of whether liver transplantation is indicated. The authors conclude that applying prognostic criteria associated with death from acute liver failure is critical in determining which patients are likely to recover and which are likely to die and should be considered for liver transplantation. 4 tables. 9 references. (AA-M). •
Chapter 39-D: Pediatric Rheumatic Diseases: Pain Syndromes Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 548-554. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This section of a chapter on pediatric rheumatic diseases provides health professionals with information on pain syndromes. All children experience pain except those with congenital indifference to it. Although most pain is of short duration and due to noxious stimuli, chronic or recurrent musculoskeletal pain can be caused by inflammation, trauma, or psychological distress. There are various presentations of childhood chronic musculoskeletal pain, including generalized and localized hypermobility, growing pains, and amplified musculoskeletal pain syndromes. Hypermobility syndrome, which usually occurs in children aged 3 to 10, is characterized by intermittent nocturnal leg pain. Although reassurance is the main treatment for hypermobility, supportive footwear and an evening dose of acetaminophen or a nonsteroidal antiinflammatory drug may be helpful. The most common areas affected by hypermobility are the pes planus, genu recurvatum, and patella. Hypermobility is treated with exercise, orthotics, and, sometimes, surgery. There are various pain amplification syndromes affecting children. These syndromes are on a continuum and frequently overlap. The etiology of amplified musculoskeletal pain in children is unknown. Some possible causes include injury, illness, and psychological distress. Factors such as age, gender, hormones, and genetics may have a role. Diagnosis is based on medical history and a physical examination. A common form of treatment for any of the pain amplification syndromes is aggressive exercise therapy. Psychotherapy may also benefit many children. Musculoskeletal pain in children may be a manifestation of other diseases, including malignancies that affect the bones or bone marrow, endocrine disorders, and genetic disorders of collagen metabolism. 4 tables and 26 references.
•
Transurethral Microwave Thermotherapy Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 1105-1109.
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Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Transurethral microwave thermotherapy is a treatment for symptomatic benign prostatic hyperplasia (BPH). This chapter on transurethral microwave thermotherapy of the prostate is from an exhaustive textbook on urologic surgery. Treatment of BPH is usually initiated because of the bothersome obstructive and irritative symptoms that interrupt normal daytime lifestyle patterns and reduce sleep. Transurethral thermotherapy is indicated for the treatment of symptomatic prostatic outflow obstruction. Patients with urinary retention, upper tract deterioration, bladder calculi (stones), and recurrent infections or gross hematuria (blood in the urine) are better treated with surgical prostatectomy. The author describes the surgical techniques used and the three transurethral thermotherapy devices currently in use (the Prostatron from EDAP Technomed, the T3 from Urologix, and the Urowave from Dornier MedTech). Patients discharged after the office treatment usually take oral antibiotics for 3 more days. Acetaminophen is sufficient for the small number of patients who complain of discomfort. Many patients notice a worsening of symptoms for several weeks until there is improvement. One of the great advantages of transurethral microwave thermotherapy is the low incidence of complications. 1 figure. 2 tables. 10 references.
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CHAPTER 8. PERIODICALS ACETAMINOPHEN
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover acetaminophen.
News Services and Press Releases One of the simplest ways of tracking press releases on acetaminophen 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 “acetaminophen” (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 acetaminophen. 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 “acetaminophen” (or synonyms). The following was recently listed in this archive for acetaminophen: •
Acetaminophen found ineffective in treating knee osteoarthritis Source: Reuters Industry Breifing Date: February 06, 2003
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LAM plans to acquire Actium's Fortex, acetaminophen products Source: Reuters Industry Breifing Date: February 04, 2003
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Study questions acetaminophen for knee arthritis Source: Reuters Health eLine Date: January 30, 2003
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Acetaminophen overdose leading liver failure cause Source: Reuters Health eLine Date: December 16, 2002
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High-dose acetaminophen not free of GI effects in the elderly Source: Reuters Industry Breifing Date: December 12, 2002
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Acetaminophen use during pregnancy may increase risk of childhood wheezing Source: Reuters Industry Breifing Date: October 29, 2002
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Acetaminophen, NSAIDs seem to increase risk of hypertension in women Source: Reuters Industry Breifing Date: October 28, 2002
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Natural steroid prevents acetaminophen-induced liver failure in mice Source: Reuters Medical News Date: October 11, 2002
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Potential new acetaminophen OD treatment strategy Source: Reuters Health eLine Date: October 10, 2002
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FDA advisors back stronger acetaminophen warning Source: Reuters Health eLine Date: September 20, 2002
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FDA advisors back stronger warning for acetaminophen Source: Reuters Industry Breifing Date: September 19, 2002
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Advisors to US FDA back stronger warning label for acetaminophen Source: Reuters Medical News Date: September 19, 2002
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NicOx cleared to begin US phase II trials of acetaminophen derivative for acute pain Source: Reuters Industry Breifing Date: September 17, 2002
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FDA approves phase II trials of acetaminophen derivative for acute pain Source: Reuters Medical News Date: September 17, 2002
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Scientists discover secret of Tylenol's success Source: Reuters Health eLine Date: September 16, 2002
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Acetaminophen may target a third cyclooxygenase Source: Reuters Medical News Date: September 16, 2002
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FDA OKs generic versions of Tylenol with codeine Source: Reuters Health eLine Date: August 02, 2002
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Able Labs gets FDA approval for generic versions of Tylenol with Codeine Source: Reuters Industry Breifing Date: August 02, 2002
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Bentley to register new versions of acetaminophen in Spain Source: Reuters Industry Breifing Date: July 16, 2002
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FDA says sponsors may market generic acetaminophen/codeine tablets Source: Reuters Industry Breifing Date: May 06, 2002
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Merck says Vioxx superior to oxycodone/acetaminophen for post-surgical dental pain Source: Reuters Industry Breifing Date: March 04, 2002
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Acetaminophen loading dose hastens fever reduction in children Source: Reuters Medical News Date: October 11, 2001
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Parental education can reduce risk of pediatric acetaminophen overdose Source: Reuters Industry Breifing Date: October 02, 2001
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MDs assess risk of Tylenol overdose in children Source: Reuters Health eLine Date: October 02, 2001
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High-dose acetaminophen associated with high risk of peptic ulcer Source: Reuters Industry Breifing Date: September 11, 2001
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Arthrotec superior to acetaminophen in some osteoarthritis patients Source: Reuters Industry Breifing Date: August 03, 2001
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High-dose acetaminophen may limit effects of ischemic stroke Source: Reuters Industry Breifing Date: July 05, 2001
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Acetaminophen lowers temperature after stroke Source: Reuters Health eLine Date: July 05, 2001
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Ibuprofen, acetaminophen equally effective for severe osteoarthritis knee pain Source: Reuters Industry Breifing Date: June 13, 2001
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FDA reviewing danger of acetaminophen ODs Source: Reuters Health eLine Date: March 28, 2001
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FDA considers relabeling of acetaminophen Source: Reuters Medical News Date: March 28, 2001
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Bentley expects $5 million in Q4 revenues, reports on acetaminophen products Source: Reuters Industry Breifing Date: February 26, 2001
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Acetaminophen hypersensitivity reactions mediated by IgE Source: Reuters Industry Breifing Date: January 26, 2001 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “acetaminophen” (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 “acetaminophen” (or synonyms). If you know the name of a company that is relevant to acetaminophen, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.
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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “acetaminophen” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “acetaminophen” (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 acetaminophen: •
Arthritis Cure: Does It Really Work? Source: University of California at Berkeley Wellness Letter. 13(8):1-2,5; May 1997. Contact: Available from Health Letter Associates, P.O. Box 412, Prince Street Station, New York, NY 10012-0007. Summary: This newsletter article for individuals with osteoarthritis critiques a book that offers advice for managing osteoarthritis (OA). Although the book provides some standard advice for managing OA, it also claims that OA suffers will experience relief from their symptoms by taking the nutritional supplements glucosamine and chondroitin sulfate. The book even proclaims that some individuals may have a complete reversal of arthritis through the rebuilding of cartilage. The article explains why this claim is inaccurate. It also offers suggestions for preventing and treating OA, including adopting a regular exercise program, maintaining a healthy weight, and using acetaminophen and nonsteroidal anti-inflammatory drugs.
•
Prescribed Medications Source: Fibromyalgia Frontiers. 9(3): 17-22. 2001. Contact: Available from National Fibromyalgia Partnership, Inc. 140 Zinn Way, Linden, VA 22642-5609. (866) 725-4404 toll-free. Fax (540) 622-2998. E-mail:
[email protected]. Website: www.fmpartnership.org. Summary: This newsletter article provides health professionals and people who have fibromyalgia (FM) with information on prescription and nonprescription medications that can relieve pain and improve sleep and mood. Categories of drugs used in the treatment of fibromyalgia are analgesics, antiinflammatory drugs, antidepressant medications, muscle relaxants, sleep modifiers, antianxiety medicines, and other medicines used to treat chronic pain. Analgesics are pain killers and can include nonprescription medicines such as aspirin and acetaminophen or prescription strength pain pills such as narcotics, codeine, Vicodin, Darvocet, Oxycontin, and Percocet. Antiinflammatory medicines include aspirin, nonsteroidal antiinflammatory drugs, and corticosteroids. Antidepressant medications include tricyclics and selective serotonin reuptake inhibitors. Muscle relaxants can decrease pain in people who have FM and
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include Flexeril, Soma, Skelaxin, and Robaxin. Various medications can be used to treat insomnia, including benzodiazepines and hypnotic nonbenzodiazepines. Anxiety is a common problem in FM, but various medicines, including antidepressants and muscle relaxants, can treat it. Other medicines used to treat pain include antiseizure medicines, headache medications, and antibiotics. The article highlights the beneficial and adverse effects of each drug category. In addition, the article presents basic strategies regarding medication use and discusses the use of trigger point injections to manage pain. •
What To Do About a Pain in the Neck Source: Mayo Clinic Women's HealthSource. 4(1): 6. January 2000. Contact: Available from Mayo Clinic Women's HealthSource, 200 First Street SW, Rochester, MN 55905. (800) 876-8633 or (303) 604-1465. Email:
[email protected]. Summary: This newsletter article provides the general public with information on ways to keep the neck as flexible and pain free as possible. Adults eventually feel some effect on their neck of wear and tear arthritis. Bony spurs can form when osteoarthritis (OA) causes the neck cartilage to thin and lose elasticity. These spurs often grow in spots where they limit neck motion. Pain from OA can also cause a person to change his or her neck and head position and tense muscles, thus leading to more pain. Some types of neck pain should be treated by a physician, but neck pain that is manageable may be treated by taking acetaminophen or nonsteroidal antiinflammatory drugs, getting a good night's sleep, applying a cold pack for 10 to 20 minutes several times a day, and walking on a regular basis. The article offers some suggestions for preventing neck problems.
Academic Periodicals covering Acetaminophen Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to acetaminophen. In addition to these sources, you can search for articles covering acetaminophen 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 acetaminophen. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with acetaminophen. 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 acetaminophen: 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
Antihistamines, Decongestants, and Analgesics •
Systemic - U.S. Brands: Aclophen; Actifed Cold & Sinus; Actifed Cold & Sinus Caplets; Actifed Sinus Nighttime; Actifed Sinus Nighttime Caplets; Alka-Seltzer Plus Allergy Medicine Liqui-Gels; Alka-Seltzer Plus Cold Medicine; Alka-Seltzer Plus Cold Medicine Liqui-Gels; Allerest http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202062.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
Caffeine •
Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html
Decongestants and Analgesics •
Systemic - U.S. Brands: Actifed Sinus Daytime; Actifed Sinus Daytime Caplets; Advil Cold and Sinus; Advil Cold and Sinus Caplets; Alka-Seltzer Plus Sinus Medicine; Allerest No-Drowsiness Caplets; Aspirin-Free Bayer Select Sinus Pain Relief Caplets; BC Cold Powder Non-Drowsy Fo http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202184.html
Headache Medicines, Ergot Derivative-Containing •
Systemic - U.S. Brands: Cafergot; Cafertine; Cafetrate; D.H.E. 45; Ercaf; ErgoCaff; Ergomar; Ergostat; Gotamine; Migergot; Wigraine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202216.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
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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
Racemethionine •
Systemic - U.S. Brands: M-Caps; Pedameth; Uracid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202727.html
Sumatriptan •
Systemic - U.S. Brands: Imitrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202665.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
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Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to acetaminophen by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “acetaminophen” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for acetaminophen: •
acetylcysteine (trade name: Acetadote) http://www.rarediseases.org/nord/search/nodd_full?code=1139
•
Acetylcysteine (trade name: Acetadote) http://www.rarediseases.org/nord/search/nodd_full?code=1210
•
Acetylcysteine (trade name: Mucomyst/Mucomyst 10 LV) http://www.rarediseases.org/nord/search/nodd_full?code=511
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “acetaminophen” (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 9728 40 1007 25 216 11016
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 “acetaminophen” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
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Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Acetaminophen In the following section, we will discuss databases and references which relate to the Genome Project and acetaminophen. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “acetaminophen” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for acetaminophen: •
Acetaminophen Metabolism Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?100675 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “acetaminophen” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “acetaminophen” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on acetaminophen 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 acetaminophen. 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 acetaminophen. 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 “acetaminophen”:
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Other guides Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Children's Health http://www.nlm.nih.gov/medlineplus/childrenshealth.html Infant and Toddler Health http://www.nlm.nih.gov/medlineplus/infantandtoddlerhealth.html Medicines http://www.nlm.nih.gov/medlineplus/medicines.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 acetaminophen. 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: •
Reye's Syndrome Source: Cedar Grove, NJ: American Liver Foundation. 1997. 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) 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: A recently recognized childhood disease, Reye's syndrome is a rare complication of common respiratory infections, including chickenpox. This fact sheet from the American Liver Foundation (ALF) offers a brief overview of Reye's syndrome. Reye's syndrome should be suspected when vomiting begins 3 to 7 days after the onset of flu or chickenpox. Usually the vomiting becomes increasingly severe over a period of 8 to 12 hours. If the vomiting is associated with signs of disordered brain function, such as staring spells, stupor, delirium, or strange behavior, a medical examination. The fact sheet notes that Reye's syndrome can occur at any time, but it is most frequent during winter months, in association with influenza and similar respiratory infections. Diagnosis of Reye's syndrome is accomplished through the patient's recent history of flu like illness, persistent vomiting, elevation of certain liver enzymes (serum SGPT) with a normal bilirubin, and exclusion of meningitis and encephalitis. Almost all cases of
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Reye's syndrome have increased serum concentrations of certain liver enzymes, notably serum glutamic pyruvic transaminase (SGPT). The fact sheet notes that aspirin may contribute to the problem of Reye's syndrome; until conclusive evidence is obtained, doctors advise against the use of aspirin in chickenpox and during outbreaks of flu like illness. The fact sheet concludes with a list of medications that contain salicylates, including cold medications. Acetaminophen is the preferred antifever medicine during chickenpox and flu illnesses in children. The fact sheet offers the contact information for ALF (800-GO-LIVER, www.liverfoundation.org ). •
Analgesics and Your Kidneys Source: New York, NY: National Kidney Foundation, Inc. 199x. 3 p. Contact: Available from National Kidney Foundation. U.S. Materials Orders, 30 East 33rd Street, New York, NY 10016. (212) 889-2210. Fax (212) 689-9261. PRICE: $7.00 for 25 copies. Item number: 02-43. Summary: Many analgesic medicines (painkillers) are available over the counter (without a prescription). These medicines are generally safe when taken as directed. However, their heavy or long-term use may harm the kidneys. Up to an estimated 8 to 10 percent of the new cases of chronic kidney failure each year may be caused by chronic overuse of these medicines. This fact sheet answers common questions about analgesics and the kidneys. Topics include a definition of analgesics, how analgesics can affect the kidneys, the safety of aspirin, painkillers recommended for people with kidney disease, NSAIDs (nonsteroidal anti-inflammatory drugs), how to know if analgesics have affected one's kidneys, and other side effects from taking aspirin and NSAIDs. The fact sheet stresses that kidney disease caused by analgesics is preventable and provides some suggestions for keeping the kidneys healthy. Suggestions include: do not use over the counter painkillers more than 10 days for pain or more than 3 days for fever; avoid prolonged use of analgesics that contain a mixture of painkilling ingredients (such as aspirin, acetaminophen, and caffeine); while taking analgesics, increase the amount of fluids taken; and work closely with a health care provider to prevent drug-related kidney disease. (AA-M).
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Handout on Health: Osteoarthritis Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2002. 40 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 toll-free or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-250 HH (booklet), or AR-250L HH (large print fact sheet). Summary: This booklet uses a question and answer format to provide people who have osteoarthritis (OA) with information on the symptoms, diagnosis, and treatment of this degenerative joint disease. OA, which mostly affects the cartilage, causes pain, stiffness, swelling, and loss of motion of the joint. OA occurs most often in the hands, knees, hips, or spine. The disease affects more than 20 million people in the United States, and by 2030, about 70 million Americans will be at risk for OA. It is one of the most frequent causes of physical disability among adults, particularly those age 65 or older. Although the exact cause of OA is unknown, scientists suspect a combination of factors, including excess weight, the aging process, joint injury, and stresses on the joints from certain jobs and sports activities. In addition to physical problems, OA can affect finances and
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lifestyles. Diagnosis is based on clinical history, a physical examination, and tests. The goals of treatment are to improve joint care, maintain an acceptable body weight, control pain, and achieve a healthy lifestyle. OA treatment plans can involve exercise; rest and joint care; pain relief; weight control; medications such as acetaminophen, nonsteroidal antiinflammatory drugs, topical pain relievers, mild narcotic painkillers, corticosteroids, and hyaluronic acid; surgery; and nontraditional treatment approaches such as acupuncture, folk remedies, and nutritional supplements. Self care is the foundation of successful management of the pain and disability of OA. Programs that help people learn about OA, learn self care, and maintain a positive attitude include patient education programs, arthritis self management programs, and arthritis support groups. Regular exercise is also important in self care and wellness. The booklet describes the keys areas of OA research being supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other components of the National Institutes of Health, including animal models, diagnostic tools, genetic studies, tissue engineering, comprehensive treatment strategies, new drug therapies, and nutritional supplements. The booklet includes a list of additional resources as well. 4 figures. •
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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What is Lupus? Source: Washington, DC: Lupus Foundation of America. 2002. 6 p. Contact: Available from Lupus Foundation of America. 2000 L. St., Suite 710, Washington, DC 20036-4916. (202) 349-1155 or (800) 558-0121. (800) 558-0231 (information in Spanish). Fax: (202) 349-1156. Website: www.lupus.org. Summary: This brochure discusses lupus, a chronic autoimmune condition that affects various parts of the body including the skin, joints, blood, and kidneys. Scientists believe that both environment and genetics play a role in triggering lupus. Lupus is more common in women. There are three types of lupus: discoid or cutaneous (DL), systemic (SL), and drug-induced. DL is limited to the skin and characterized by a rash
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that appears on the scalp, neck, or face but does not involve the body's internal organs. SL is generally more severe than DL and affects organs and systems in the body. Druginduced lupus can occur after using certain prescription drugs and is found primarily in men. The symptoms of drug-induced lupus are similar to those of SL. The most common symptoms of lupus and criteria used to diagnosis lupus are listed. Tests used to diagnose lupus include the lupus erythematosus test and the immunofluorescent antinuclear antibody test. Treatment for lupus focuses on reducing symptoms and inflammation and maintaining normal body functions. Medications are prescribed based on the organs involved and the severity of this involvement. Commonly prescribed medications include NSAIDs, acetaminophen, corticosteroids, antimalarials, immunomodulating drugs, and anticoagulants. The brochure also discusses pregnancy and lupus as well as the prognosis for patients with lupus. 2 tables. •
Aspirin and Other NSAIDs Source: Atlanta, GA: Arthritis Foundation. 1997. 16 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. http://www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter; bulk orders may be purchased from address above. Summary: This brochure for people with arthritis and related conditions uses a question and answer format to provide information about the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) to treat these diseases. It notes the similarity in action and side effects of the many types of NSAIDs. Background information and guidelines for using aspirin, including side effects and consultation with a physician are discussed in some detail. The use of acetaminophen, which can also be used to relieve pain, but does not reduce inflammation associated with many forms of arthritis, is also addressed. The brochure offers general advice for taking NSAIDs and provides information on the Arthritis Foundation. 2 charts.
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Guide to Children's Medications Source: Elk Grove Village, IL: American Academy of Pediatrics. 1999. [8 p.]. Contact: Available from American Academy of Pediatrics. Division of Publications, 141 Northwest Point Blvd., P.O. Box 747, Elk Grove Village, IL 60009-0747. (800) 433-9016. Fax (847) 228-1281. E-mail:
[email protected]. Website: www.aap.org. PRICE: $34.95 per pack of 100 brochures (nonmembers); $29.95 per pack of 100 brochures (members). Summary: This brochure provides parents with a guide to prescription and over the counter (OTC) children's medications and when and how to use them. Prescription medications must be ordered by a doctor, and the brochure lists questions parents should ask the physician or pharmacist about prescriptions. The brochure discusses the drug label and how to read it; an illustration points out the parts of each label. The brochure then reviews common prescription medications for children, including antibiotics; ear, eye, and skin preparations; analgesics; and inhalers. The section on OTC medications reminds readers that even though they are available without a prescription, these medications can be very dangerous if given incorrectly. Common OTC medications for children, include fever reducers or pain relievers (acetaminophen, ibuprofen), antihistamines, mild cortisone cream, cough syrups, cold remedies, nose drops (saline and decongestant), and medications used for common gastrointestinal problems. Another section helps parents measure and administer liquid medicines and prevent overdose or poisoning. One sidebar cautions readers about the link between
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aspirin and Reye's syndrome, a serious and sometimes fatal liver disorder in children. Another sidebar reminds parents to keep a small bottle of syrup of ipecac on hand in case of poisoning; syrup of ipecac is used to induce vomiting. The brochure concludes with a brief description of the American Academy of Pediatrics and the publications it makes available. 1 figure. •
What a Pain! Kids and Growing Pains Source: KidsHealth. December 2002. 2 p. Contact: Available from KidsHealth website: www.kidshealth.org. Summary: This fact sheet discusses growing pains in children. Growing pains are muscular pains felt most often in the thighs, calves, or behind the knees. These pains affect children aged 3 to 5 or aged 8 to 12 most often. Pain usually occurs at night, either when the child goes to bed or waking the child up in the middle of the night and may be due to tiring leg muscles during the day. The pain is usually gone in the morning. Treatment for growing pains includes nonprescription medications such as acetaminophen and ibuprofen. Heat, stretching, and massage may help diminish the pain. If pain is accompanied by swelling, fever, or limping, the child should be taken to the doctor.
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Plantar Fasciitis: A Common Cause of Heel Pain Source: American Academy of Family Physicians. March 2003. 2 p. Contact: Available online from American Academy of Family Physicians. Website: http://familydoctor.org. Summary: This fact sheet discusses plantar fasciitis, a condition in which the plantar fascia (the band that connects the heel bone to the base of the toes) becomes damaged, causing heel pain. Discomfort from plantar fasciitis usually begins as a sharp pain on the bottom of the foot. Over time, the pain becomes a dull ache. Reducing the amount of walking or running, taking nonprescription medications such as acetaminophen and ibuprofen, using orthotic inserts in shoes, losing weight, and doing stretching exercises can help manage the pain. If these treatments do not lessen symptoms, the doctor may suggest night splints, corticosteroid injections, or surgery.
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Botulinum Toxin Injections: A Treatment for Muscle Spasms Source: American Academy of Family Physicians. February 2003. 2 p. Contact: Available online from American Academy of Family Physicians. Website: http://familydoctor.org. Summary: This fact sheet discusses the use of botulinum toxin to stop muscle spasms that occur in the face, head, or eye. This treatment is used for a number of conditions including spasmodic torticollis and lazy eye. The botulinum toxin is administered by injection in small doses and works by stopping the chemical messages sent from nerves. Soreness at the injection sight may occur after treatment and can be treated with nonprescription medications such as acetaminophen or ibuprofen or with an ice pack. Other short-term side effects may include weakness in the injected muscles, rash, muscle soreness throughout the body, or difficulty swallowing.
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Tips to Improve Your Clinic's Immunization Rates Source: St. Paul, MN: Immunization Action Coalition. 1997. 2 p.
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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 provides clinic administrators and nursing coordinators with a list of tips to improve the clinic's immunization rates. Although the suggestions were written primarily to increase immunization rates of children, many of them apply to adult patients as well. The fact sheet lists 35 items; before each item are three boxes for readers to indicate whether or not the clinic does that task, or if it should be considered. Topics covered include recordkeeping and paperwork, providing parents with recommended schedules, training for contraindications for vaccination, empowering nurses with standing orders to vaccinate, screening patients in the waiting room, providing a shot record card for the parents (or adult patient), the use of acetaminophen for certain vaccines (DTP or MMR), reviewing the patient's immunization status, patient selection for the hepatitis B vaccine, referring to city or county health departments, and the need to offer additional immunization clinic hours. A number of the suggestions are supported with additional printed materials available from the Immunization Action Coalition. •
After the Shots: What to Do if Your Child Has Discomfort Source: St. Paul, MN: Immunization Action 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 provides parents with information about handling a postimmunization reaction in their child. The fact sheet notes that many of the shots that protect children from serious diseases can also cause discomfort for a while. The fact sheet offers suggestions for managing the fussiness, fever, and pain their children may experience after they have been immunized. Parents are also encouraged to call their clinic or health care provider with any additional questions. Topics covered include the role of acetaminophen, the importance of not giving aspirin, taking the child's temperature, recommendations for reducing a fever, and the appropriate dosage (by child's weight and age) of acetaminophen. One sidebar lists symptoms that should prompt a call to the health care provider. 1 figure. (AA-M).
•
Osteoarthritis Source: American College of Rheumatology. 2000. 2 p. Contact: American College of Rheumatology. 1800 Century Place, Suite 250, Atlanta, GA 30345. (404) 633-3777. Website: www.rheumatology.org. Email:
[email protected]. Summary: This fact sheet provides patients with information on osteoarthritis (OA), the most common form of arthritis caused by wear and tear on the cartilage in the joints. OA affects middle-aged and older people most often. More than 21 million Americans have this disorder, and it is the leading cause of disability in the United States. Treatment for OA includes nonprescription pain relievers such as acetaminophen for milder cases. As the pain increases, NSAIDs and steroids may be used. Physical therapy is used to maintain joint flexibility, function, and strength. If these methods are unsuccessful in alleviating pain and maintaining function, joint replacement may be recommended.
•
Managing Pain Source: Journal of the American Medical Association. JAMA. 283(13): 1778. April 5, 2000.
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Contact: Available also online from American Medical Association at www.amaassn.org/consumer.htm. Summary: This fact sheet provides people who experience pain with information on managing it. Some diseases and conditions cause sudden and severe pain, whereas others cause chronic and sometimes disabling pain. Common types of pain are headache, arthritis, low back, and cancer pain. Some drugs used to treat pain include acetaminophen, antiinflammatory drugs, and opioid based drugs. Other treatment modalities include physical and psychological therapy and relaxation techniques. The fact sheet identifies sources of additional information. 1 figure. •
Well-Connected: Osteoarthritis Source: New York, NY: Nidus Information Services, Inc. 1998. 8 p. Contact: Available from Nidus Information Services, Inc. 175 Fifth Avenue, Suite 2338, New York, NY 10010. (800) 334-WELL or (212) 260-4268. Fax (212) 529-2349. E-mail:
[email protected]. Website: www.well-connected.com. PRICE: $5.95 plus shipping and handling. Summary: This fact sheet uses a question and answer format to provide people who have osteoarthritis with information on this degenerative joint disease. The fact sheet begins by describing the general features of osteoarthritis and the specific features of osteoarthritis of the fingers, knees, hips, and spine. This is followed by a discussion of the symptoms of osteoarthritis, focusing on pain. A few of the most common disorders that can be confused with osteoarthritis are then identified. These include rheumatoid arthritis, chondrocalcinosis, and Charcot's joints. Other topics include risk factors for osteoarthritis, including aging, obesity, heavy labor, and vitamin D deficiency, and causes of osteoarthritis, namely genetic factors, muscle weakness, anatomical abnormalities, trauma, and obesity. The fact sheet next outlines ways to prevent or slow the progression of osteoarthritis, including losing weight, exercising, undergoing hormone replacement therapy, and consuming adequate amounts of antioxidant vitamins and other important nutrients. This is followed by a discussion of the use of xrays, blood tests, and tests of the synovial fluid to confirm the diagnosis of osteoarthritis. Lifestyle measures for managing osteoarthritis are detailed: occupational changes, exercise, weight reduction, heat therapy, mechanical aids, alternative treatments, the arthritis self-help course, and cognitive behavioral therapy. Also discussed are the drug treatments for osteoarthritis: common pain relievers such as acetaminophen and nonsteroidal anti-inflammatory drugs; drugs derived from natural joint substances such as hyaluronic acid, glucosamine, and chondroitin sulfate; capsaicin; steroids; and gene therapy. Surgical treatments for osteoarthritis are also highlighted, including arthroscopy, resection arthroplasty, osteotomy, chondroplasty, arthrodesis, and joint replacement. The article concludes with comments on the emotional ramifications of osteoarthritis and a list of helpful organizations.
•
Arthritis: What It Is and How To Live With It Source: Seattle, WA: Hope Heart Institute. 199x. 20 p. Contact: Available from International Health Awareness Center, Inc. 350 East Michigan, Suite 301, Kalamazoo, MI 49007-3851. (800) 334-4094 or (616) 343-0770. Website: www.hithope.com. PRICE: Single copy $4.95 plus shipping and handling; bulk orders available. Item Number: 426.
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Summary: This illustrated booklet provides people who have arthritis with an overview of this chronic condition. Although there are over 100 different diseases that are considered arthritis, the most common are osteoarthritis (OA), rheumatoid arthritis (RA), lupus, spondyloarthropathies, and gout. The booklet explains how normal joints work, lists the warning signs of arthritis, compares the features of OA and RA, outlines the causes and symptoms of OA, offers suggestions on preventing or minimizing OA, discusses the importance of exercise in managing OA, provides examples of range of motion exercises, and presents tips on getting the most out of exercise. Other topics include maintaining a healthy diet; working with the pain; and using treatments such as aspirin and acetaminophen, hot and cold packs, ointments and creams, and unproven remedies. In addition, the booklet offers tips on making life with arthritis easier and provides sources of additional information. •
How to Care for Your Ankle Sprain Source: American Family Physician. 57(3): 485-486. February 1, 1998. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail:
[email protected]. Website: www.aafp.org. Summary: This journal article for people who have sprained their ankle uses a question and answer format to provide them with information on how to care for the sprain. This type of injury occurs when the foot rolls or turns in on itself, and the ligaments that hold the ankle and foot bones in place are stretched and weakened. The RICE treatment is recommended after a sprain. RICE stands for resting the injured extremity, icing the injury to reduce swelling, compressing the injured area to decrease swelling and provide support, and elevating the injured extremity to decrease pain and swelling. Effective pain medications include antiinflammatory medicines such as ibuprofen, naprosyn, or ketoprofen. Acetaminophen may also be used. Once the sprain heals, exercises should be performed to help strengthen the ankle and prevent another injury. The article describes exercises people can perform following an ankle sprain and recommends ways to prevent another ankle sprain.
•
Sickle cell disease related pain: Assessment and management: Quick reference guide for clinicians Source: Mount Desert, ME: New England Regional Genetics Group. 1994. 30 pp. Contact: Available from Victoria Odesina, New England Regional Genetics Group, P.O. Box 670, Mt. Desert, ME 04660. Telephone: (207) 288-2704 / fax: (207) 288-2705 / e-mail:
[email protected] / Web site: http://www.acadia.net/nergg. Available at no charge. Summary: This pamphlet advises doctors on working with patients with sickle cell disease pain. It discusses how to relate to the patient according to age, education, and culture. It mentions adaptations to communication problems, such as might be caused by mental or emotional problems. Chapters discuss pain assessment, acetaminophen and non-steroid anti-inflammatory drugs, opiates, tolerance and dependence, acute and chronic pain management, home and hospital treatment, and alternative treatments. There is a short reference list, and a list of participants at the conference in 1993 at which these recommendations were prepared. [Funded by the Maternal and Child Health Bureau].
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Dyspepsia: What It Is and What to Do About It Source: American Family Physician. 60(6): 1787. October 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 care handout describes dyspepsia and the treatments that are available to manage it. Dyspepsia is a pain or an uncomfortable feeling in the upper middle part of the stomach; the pain might come and go but is usually persistent. Some of the signs of dyspepsia include gnawing or burning stomach pain, bloating (a feeling of fullness in the stomach), heartburn (stomach contents coming back up into the throat), upset stomach (nausea), vomiting, and burping. Often, dyspepsia is caused by a stomach acid or acid reflux disease (in the latter, stomach acid backs up into the esophagus, which causes pain). Most often, medicine can take care of this condition. If there is a stomach ulcer, it can be cured; sometimes an acid blocking medicine is needed, and antibiotics are used to eliminate infections in the stomach. In some cases, medications cause dyspepsia, so patients need to work with their physicians to find alternative treatments. Endoscopy is used to evaluate patients who still have stomach pain after taking dyspepsia medications for 8 weeks, or for those with recurrent pain. The medications used for dyspepsia most often have only minor side effects (if any). The handout concludes with a list of lifestyle strategies that can help readers avoid dyspepsia: stop smoking, avoid foods that seem to make the dyspepsia worse, reduce stress, do not eat just before bedtime, raise the head of the bed, and try to avoid antiinflammatory medications such as ibuprofen, aspirin, naproxen, and ketoprofin (use acetaminophen instead).
•
Hemorrhoids: Reducing the Pain and Discomfort Source: Kansas City, MO: American Academy of Family Physicians. 1994. 4 p. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. PRICE: $22.00 for 100 copies for members, $33.00 for 100 copies for nonmembers. Summary: This patient education brochure helps readers understand hemorrhoids and what to do to reduce the pain and discomfort they may cause. Hemorrhoids are swollen veins in the rectum or anus. Internal hemorrhoids involve the veins inside the rectum; external hemorrhoids involve veins in the skin outside the anus. One of the main things that can lead to hemorrhoids is straining while trying to have a bowel movement. Other risk factors for hemorrhoids include genetics (inherited tendency to have hemorrhoids), pregnancy, obesity, and standing or lifting too much. A health care provider should be consulted for any rectal bleeding, in order to rule out more serious causes and possibly to treat the hemorrhoids. One sidebar provides suggestions for preventing constipation, including increasing dietary fiber, drinking plenty of fluids, and exercising regularly. Strategies for the home care management of hemorrhoids are also outlined. These include: soaking in a warm bath, cleaning the anus carefully after each bowel movement, using ice packs to relieve swelling, using acetaminophen or aspirin to relieve pain, and using a cream or ointment to sooth and numb itching and pain. The brochure concludes with a brief description of the surgical treatments for hemorrhoids and the indications for surgery. 1 figure. 2 tables. (AA-M).
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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to acetaminophen. 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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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to acetaminophen. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with acetaminophen. 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 acetaminophen. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at
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http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “acetaminophen” (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 “acetaminophen”. 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 “acetaminophen” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “acetaminophen” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.25
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
25
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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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/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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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
•
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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on acetaminophen: •
Basic Guidelines for Acetaminophen Acetaminophen overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002598.htm Tylenol #3 overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002562.htm
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Signs & Symptoms for Acetaminophen Bluish skin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Breathing difficulties Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm
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Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Muscle spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Nausea and/or vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Pain in the stomach Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Sweating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Upset stomach Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weak pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003078.htm •
Diagnostics and Tests for Acetaminophen Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm
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Background Topics for Acetaminophen Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm
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Breathing shallow Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm Breathing slow and labored Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Unconscious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm
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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ACETAMINOPHEN 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] Ablation: The removal of an organ by surgery. [NIH] Academic Medical Centers: Medical complexes consisting of medical school, hospitals, clinics, libraries, administrative facilities, etc. [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] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acupuncture Points: Designated locations along nerves or organ meridians for inserting acupuncture needles. [NIH]
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Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adduction: The rotation of an eye toward the midline (nasally). [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]
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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] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [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] 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] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is
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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] 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] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alendronate Sodium: A drug that affects bone metabolism. It is used in treating osteoporosis and Paget's disease, and is being studied in the treatment of hypercalcemia (abnormally high levels of calcium in the blood) and in treating and reducing the risk of bone pain caused by cancer. Alendronate sodium belongs to the family of drugs called bisphosphonates. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This
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is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH]
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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] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] 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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antianginal: Counteracting angina or anginal conditions. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [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]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [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
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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] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [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] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic
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and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] 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] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apnea: A transient absence of spontaneous respiration. [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] Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be
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associated with malignant hypertension, nephrosclerosis, and scleroderma. [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] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] 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] Aspartate: A synthetic amino acid. [NIH] Aspartate Transaminase: An enzyme of the transferase class that catalyzes the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] 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] Attenuated: Strain with weakened or reduced virulence. [NIH]
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Auditory: Pertaining to the sense of hearing. [EU] Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Barbital: A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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]
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Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [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 Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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
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tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] 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] Bladder: The organ that stores urine. [NIH] Bladder Calculi: Calculi of the urinary bladder; also known as vesical calculi or bladder stones, and cystoliths. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood 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
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junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the
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benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the
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interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH]
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Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] 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] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] 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] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief
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constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] 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] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] 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] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chlormethiazole: A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate gaba receptors response and it may also affect glycine receptors. [NIH] Chlorpheniramine: A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine. [NIH]
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Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholelithiasis: Presence or formation of gallstones. [NIH] 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 Oxidase: An enzyme that catalyzes the oxidation of cholesterol in the presence of molecular oxygen to 4-cholesten-3-one and hydrogen peroxide. The enzyme is not specific for cholesterol, but will also oxidize other 3-hydroxysteroids. EC 1.1.3.6. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is
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active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clemastine: Histamine H1 antagonist used as the hydrogen fumarate in hay fever, rhinitis, allergic skin conditions, and pruritus. It causes drowsiness. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] 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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Implantation: Surgical insertion of an electronic device implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The
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cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [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] 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] 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] Colloidal: Of the nature of a colloid. [EU] 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
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as massage therapy, magnet therapy, spiritual healing, and meditation. [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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of
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organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a
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myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] 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] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme
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combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decongestant: An agent that reduces congestion or swelling. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or
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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] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] 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] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other
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holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Didanosine: 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. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [NIH] Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to didanosine (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. [NIH] Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive 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] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [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] Dimenhydrinate: A drug combination that contains diphenhydramine and theophylline. It is used for treating vertigo, motion sickness, and nausea associated with pregnancy. It is not
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effective in the treatment of nausea associated with cancer chemotherapy. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discoid: Shaped like a disk. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [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] Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties. [NIH] Dithionite: The dithionous acid ion and its salts. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH]
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Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [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] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH]
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Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] 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] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] Emetine: The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein syntheis in eucaryotic but not prokaryotic cells. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH]
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Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-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] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] 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]
Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH]
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Enzyme 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] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Ergot Alkaloids: Alkaloids isolated from the ergot fungus Claviceps purpurea (Hypocreaceae). The ergot alkaloids were the first alpha-adrenergic antagonists discovered, but side effects generally prevent their administration in doses that would produce more than a minimal blockade in humans. Their smooth muscle-stimulating activities may be attributed to alpha-agonistic properties, thus characterizing these alkaloids as a series of partial agonists. They have many clinical applications, notably in obstetrics and the treatment of migraine. (From Martindale, The Extra Pharmacopoeia, 28th ed, p662). [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical
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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] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [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] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excrete: To get rid of waste from the body. [NIH] Exercise Therapy: Motion of the body or its parts to relieve symptoms or to improve function, leading to physical fitness, but not physical education and training. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]
Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH]
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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] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [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] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Flatus: Gas passed through the rectum. [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] Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting carbonic anhydrase. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Fold: A plication or doubling of various parts of the body. [NIH]
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Follicles: Shafts through which hair grows. [NIH] Foot Bones: The tarsus, metatarsus, and phalanges. The tarsus consists of seven bones: calcaneum, astragalus, cuboid, navicular, internal, middle, and external cuneiform bones. The five metatarsal bones are numbered one through five, running medial to lateral. There are 14 phalanges in each foot, the great toe has two while the other toes have three each. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [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-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH]
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Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrointestinal Transit: Passage of food (sometimes in the form of a test meal) through the gastrointestinal tract as measured in minutes or hours. The rate of passage through the intestine is an indicator of small bowel function. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [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] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or
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participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]
Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronate: Salt of glucuronic acid. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate-Cysteine Ligase: One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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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] 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 molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] 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] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] 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] Haematemesis: The vomiting of blood. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half
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of its pharmacologic, physiologic, or radiologic activity. [NIH] Haloperidol: Butyrophenone derivative. [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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] 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] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH]
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Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemosiderin: Molecule which can bind large numbers of iron atoms. [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 usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatic Veins: Veins which drain the liver. [NIH] Hepatic Veno-Occlusive Disease: Blockage of the small- or medium-sized hepatic veins due to nonthrombotic subendothelial edema which may progress to fibrosis. [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, Chronic: A collective term for a clinical and pathological syndrome which has several causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. Specific forms of chronic hepatitis include autoimmune hepatitis, chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, indeterminate chronic viral hepatitis, cryptogenic chronic hepatitis, and drug-related chronic hepatitis. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH]
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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]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotropic: Of organisms that cannot live without an external source of organic food. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrocodone: Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [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]
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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] Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [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] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Portal: Abnormally increased pressure in the portal venous system; frequently seen in cirrhosis of the liver and in other conditions which cause obstruction of the portal vein. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU]
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Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] 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] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
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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] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of
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neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] 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] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and
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fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interindividual: Occurring between two or more individuals. [EU] 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-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH]
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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] 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 or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] Ipecac: A syrup made from the dried rhizomes of two different species, Cephaelis ipecacuanha and C. acuminata, belonging to the Rubiaciae family. They contain emetine, cephaeline, psychotrine and other isoquinolines. Ipecac syrup is used widely as an emetic acting both locally on the gastric mucosa and centrally on the chemoreceptor trigger zone. [NIH]
Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] 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] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH]
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Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to indomethacin. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH]
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Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]
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Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] 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 Neoplasms: Tumors or cancer of the liver. [NIH] Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [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] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph
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nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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]
Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Melanin: The substance that gives the skin its color. [NIH]
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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] 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] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic 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] Metalloporphyrins: Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds. [NIH] Metatarsal Bones: The five long bones of the metatarsus articulating with the tarsal bones
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proximally and the toes (phalanges) distally. [NIH] Metatarsus: The part of the foot between the tarsa and the toes. [NIH] Methacrylate: A vinyl monomer. [NIH] Methapyrilene: Histamine H1 antagonist with sedative action used as a hypnotic and in allergies. [NIH] 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] 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] 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] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] 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] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH]
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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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] 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] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] 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 nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] 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] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle 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 tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness,
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malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] 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] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] N-acetyl: Analgesic agent. [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] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] 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] Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial
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swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [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] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] 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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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,
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and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] 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] Nonoxynol: Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Nonoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide, formulated primarily as a component of vaginal foams and creams. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the
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chromosomes. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] 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] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] 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] Orphenadrine: A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an
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excessive dose. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaloacetate: An anionic form of oxaloacetic acid. [NIH] Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative 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] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and
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the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] 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] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and
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muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patella: The flat, triangular bone situated at the anterior part of the knee. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Pentachlorophenol: An insecticide and herbicide that has also been used as a wood preservative. Pentachlorphenol is a widespread environmental pollutant. Both chronic and acute pentachlorophenol poisoning are medical concerns. The range of its biological actions is still being actively explored, but it is clearly a potent enzyme inhibitor and has been used as such as an experimental tool. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into
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contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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] Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [NIH] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral 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] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH]
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P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [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] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] 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] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipases A: Phosphatide acylhydrolases. Catalyze the hydrolysis of one of the acyl groups of phosphoglycerides or glycerophosphatidates. Phospholipase A1 hydrolyzes the
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acyl group attached to the 1-position (EC 3.1.1.32) and phospholipase A2 hydrolyzes the acyl group attached to the 2-position (EC 3.1.1.4). [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] 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] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [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] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] 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]
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Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] 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
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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 Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portosystemic Shunt: An operation to create an opening between the portal vein and other veins around the liver. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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] 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] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [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
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cirrhosis in later stages of the disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propoxyphene: A narcotic analgesic structurally related to methadone. Only the dextroisomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids
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having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] 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] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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
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C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] 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] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH]
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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]
Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrexia: A fever, or a febrile condition; abnormal elevation of the body temperature. [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyruvate Carboxylase: A biotin-dependent enzyme belonging to the ligase family that catalyzes the addition of carbon dioxide to pyruvate. It is occurs in both plants and animals. Deficiency of this enzyme causes severe psychomotor retardation and lactic acidosis in infants. EC 6.4.1.1. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [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] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH]
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Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] 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] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward
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flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue
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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] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] 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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]
Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [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] Scleroderma: A chronic disorder marked by hardening and thickening of the skin.
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Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH]
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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] 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] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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] Single-agent: The use of a single drug or other therapy. [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] Sludge: A clump of agglutinated red blood cells. [NIH]
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Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] 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] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists
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mainly of chromatin. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [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] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Steatosis: Fatty degeneration. [EU] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] 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] Stomach Ulcer: An open sore in the lining of the stomach. Also called gastric ulcer. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are
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coiled together. [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] 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] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [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] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in
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which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [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] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tarsus: The region of the articulation between the foot and the leg. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH]
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Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are antithryoid agents and/or free radical scavengers. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level
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(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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] 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]
Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] 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] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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] Tolmetin: An anti-inflammatory antipyretic and analgesic similar in mode of action to indomethacin. It has been proposed as an antirheumatic agent. [NIH]
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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 restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH] Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [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
Dictionary 291
ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] 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] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor 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] 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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH]
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Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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 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] 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] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the
Dictionary 293
inner ear. [NIH] 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] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU]
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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 vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [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] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH]
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Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yawning: An involuntary deep inspiration with the mouth open, often accompanied by the act of stretching. [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] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. 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, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
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INDEX A Abdomen, 192, 211, 222, 223, 241, 255, 258, 268, 270, 285, 288 Abdominal, 211, 268, 270 Abdominal Pain, 211, 270 Ablation, 30, 211 Academic Medical Centers, 21, 211 Acatalasia, 211, 226 Acceptor, 211, 258, 267, 276, 286, 290 Acetaldehyde, 124, 211 Acetone, 211 Acetylcholine, 211, 258, 265 Acetylcysteine, 4, 6, 31, 50, 67, 70, 71, 72, 80, 83, 89, 92, 106, 109, 114, 119, 144, 178, 211 Acidosis, 70, 211, 278 Acne, 211, 280 Acquired Immunodeficiency Syndrome, 140, 211 Acupuncture Points, 18, 212 Acute myelogenous leukemia, 23, 212 Acute myeloid leukemia, 212 Acute nonlymphocytic leukemia, 212 Acute renal, 3, 212, 249 Acute tubular, 4, 212 Acyl, 29, 135, 144, 145, 212, 272 Acylation, 144, 212 Adaptability, 212, 226 Adaptation, 212, 228, 262 Adduct, 14, 36, 40, 212 Adduction, 40, 212 Adenine, 212, 278 Adenocarcinoma, 47, 212, 249 Adenosine, 142, 212, 215, 224, 251, 272, 288 Adenylate Cyclase, 27, 212 Adhesives, 134, 212 Adjunctive Therapy, 64, 212 Adjustment, 5, 23, 212 Adjuvant, 141, 156, 212, 245 Adolescence, 33, 213, 269 Adrenal Cortex, 213, 233, 241, 275 Adrenal Glands, 213, 215 Adrenergic, 129, 213, 216, 218, 237, 241, 258, 278 Adrenergic Antagonists, 213, 241 Adsorption, 66, 213 Adsorptive, 213
Adverse Effect, 33, 41, 120, 138, 163, 174, 213, 238, 256, 283, 293 Aerobic, 20, 163, 213, 261, 267 Aerobic Exercise, 163, 213 Aerobic Metabolism, 20, 213, 267 Aerobic Respiration, 213, 267 Aerosol, 153, 213, 287, 293 Affinity, 15, 30, 37, 213, 235, 284 Agonist, 75, 151, 156, 213, 223, 224, 237, 286, 287 Agoraphobia, 214, 252, 268 Airway, 214, 294 Alanine, 130, 214 Albumin, 56, 214, 272, 287 Aldehydes, 214, 294 Alendronate, 128, 214 Alendronate Sodium, 128, 214 Alertness, 214, 224 Algorithms, 214, 222 Alimentary, 66, 214, 236, 270 Alkaline, 127, 137, 211, 214, 224, 267, 288 Alkaloid, 214, 223, 225, 229, 239, 262, 268, 278, 288 Alkylation, 124, 214 Alleles, 37, 214 Allergic Rhinitis, 60, 214 Alpha Particles, 214, 278 Alternative medicine, 21, 163, 172, 214 Ameliorating, 8, 215 Amino Acid Sequence, 215, 217 Amino Acids, 215, 219, 241, 270, 273, 277, 281, 283, 286, 291, 292 Amiodarone, 165, 215 Amnestic, 215, 243, 261 Amphetamines, 52, 215, 229 Amplification, 166, 215 Ampulla, 215, 228, 240 Amyloidosis, 162, 215 Anabolic, 159, 215 Anaesthesia, 52, 69, 74, 82, 215, 253 Anal, 34, 215 Analog, 215, 235 Analogous, 29, 215, 290 Analytes, 146, 157, 215 Anaphylactic, 46, 215 Anaphylaxis, 215 Anatomical, 196, 216, 231, 236, 252, 282 Androgens, 213, 216, 233
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Anemia, 64, 138, 162, 187, 216, 229, 248, 288, 295 Anesthesia, 53, 56, 58, 64, 72, 76, 83, 85, 214, 216, 233, 261, 275 Anesthetics, 164, 216, 220, 241 Aneurysm, 216, 293 Angina, 216, 270 Anginal, 216, 265 Animal model, 32, 35, 192, 216 Anionic, 10, 216, 267 Anions, 31, 214, 216, 255 Ankle, 197, 216 Annealing, 216, 273 Anode, 216 Antagonism, 216, 224, 288 Anthracycline, 138, 216 Antiallergic, 216, 233, 275 Antianginal, 215, 216 Anti-Anxiety Agents, 216, 274 Antiarrhythmic, 215, 216 Antibacterial, 216, 255, 284, 292 Antibiotic, 147, 216, 229, 241, 274, 281, 284, 288 Antibiotic Prophylaxis, 216, 274 Antibodies, 40, 217, 248, 252, 259, 272 Antibody, 193, 213, 217, 230, 248, 250, 252, 253, 259, 284 Anticarcinogenic, 14, 217 Anticoagulant, 75, 81, 217, 276, 277, 294 Anticonvulsant, 217, 225, 227, 258, 260, 292 Antidepressant, 173, 217, 252 Antidote, 31, 84, 119, 217 Antiemetic, 217, 218, 228, 237 Antifungal, 217, 256 Antigen, 213, 215, 217, 230, 250, 251, 252, 253, 259, 275 Antihistamine, 128, 162, 217 Anti-infective, 217, 250, 255 Anti-Inflammatory Agents, 141, 151, 155, 217, 219, 226, 233, 256 Antimicrobial, 217, 228, 235 Antineoplastic, 217, 233, 244, 271 Antineoplastic Agents, 217, 271 Antioxidant, 7, 13, 20, 92, 100, 101, 159, 196, 217, 219, 267, 283 Antipsychotic, 217, 228 Antipyretic, 13, 15, 28, 36, 44, 47, 56, 76, 124, 127, 144, 149, 211, 218, 236, 243, 256, 278, 289 Antiseptic, 211, 218, 226 Antispasmodic, 218, 266
Antitussive, 128, 218, 235, 237, 266, 275 Antiviral, 140, 165, 192, 211, 218, 244, 264 Antiviral Agents, 192, 218 Anuria, 218, 256 Anus, 198, 215, 218, 223, 270, 279 Anxiety, 162, 174, 216, 218, 243, 256, 258, 267, 268 Anxiolytic, 218, 224, 261 Apnea, 141, 218 Apoptosis, 13, 14, 21, 23, 25, 42, 48, 81, 218, 226 Aqueous, 118, 127, 128, 132, 137, 157, 218, 220, 228, 234, 240, 250, 257 Aqueous fluid, 132, 218 Arachidonic Acid, 41, 218, 234, 238, 257, 275 Arginine, 218, 265 Arterial, 158, 218, 219, 232, 251, 277, 287 Arteries, 159, 218, 219, 222, 223, 232, 255, 261, 263, 289 Arterioles, 153, 218, 219, 223, 225, 293 Arteriolosclerosis, 219 Arteriosclerosis, 61, 158, 219 Arthroplasty, 72, 196, 219 Arthroscopy, 196, 219 Articular, 219, 266 Ascites, 17, 162, 219 Ascorbic Acid, 94, 96, 132, 157, 219, 251 Aspartate, 127, 130, 219, 235 Aspartate Transaminase, 130, 219 Aspartic, 124, 219, 240 Aspartic Acid, 124, 219 Aspergillosis, 219, 256 Assay, 7, 62, 65, 77, 132, 139, 147, 219, 252, 281 Astringent, 219, 226 Asymptomatic, 211, 219, 268 Ataxia, 186, 187, 219, 288 Atrial, 215, 219, 232, 294 Atrial Fibrillation, 219, 294 Atrophy, 186, 220, 264 Attenuated, 100, 220, 236 Auditory, 26, 220 Aura, 130, 220 Autacoids, 220, 253 Autodigestion, 220, 268 Autoimmune Hepatitis, 66, 162, 220, 249 Autosuggestion, 220, 252 Azotemia, 4, 220, 292 B Babesiosis, 220, 278 Back Pain, 85, 220
Index
Bactericidal, 220, 242 Bacteriostatic, 220, 241 Bacterium, 220, 231, 249 Barbital, 124, 220 Barbiturate, 220, 232 Basal Ganglia, 218, 219, 220 Basal Ganglia Diseases, 219, 220 Base, 16, 34, 152, 157, 194, 212, 220, 235, 256, 287, 292 Basophils, 221, 247, 257 Behavioral Symptoms, 34, 221 Benign, 167, 219, 221, 248, 264 Benign prostatic hyperplasia, 167, 221 Benzene, 39, 221 Benzodiazepines, 174, 221, 224 Bilateral, 26, 71, 82, 221 Bile, 10, 19, 28, 162, 221, 228, 244, 246, 249, 256, 258, 275, 285, 286 Bile Acids, 19, 28, 221, 285, 286 Bile Acids and Salts, 221 Bile Ducts, 162, 221, 244, 275 Bile Pigments, 221, 256 Biliary, 10, 162, 163, 164, 165, 221, 224, 228, 249, 268 Biliary Atresia, 163, 221 Biliary Tract, 162, 221, 224, 268 Bilirubin, 19, 28, 190, 214, 221, 244, 246, 251 Binding Sites, 27, 156, 221 Bioavailability, 17, 31, 134, 148, 221 Biological Transport, 221, 236 Biomarkers, 32, 33, 108, 222 Biopsy, 16, 163, 222 Biosynthesis, 13, 60, 218, 222, 276, 282 Biotechnology, 44, 45, 106, 172, 183, 185, 186, 187, 222 Biotin, 222, 278 Biotransformation, 30, 32, 33, 35, 37, 39, 222, 271 Bladder, 167, 221, 222, 264, 276, 280, 292 Bladder Calculi, 167, 222 Blastocyst, 222, 231, 239, 272 Blastomycosis, 222, 256 Bloating, 198, 222, 253 Blood Cell Count, 222, 248 Blood Coagulation, 222, 224, 281, 289 Blood Glucose, 222, 248, 251, 254 Blood Platelets, 222, 283, 289 Blood pressure, 52, 208, 212, 222, 225, 227, 251, 262, 265, 284 Blood-Brain Barrier, 223, 257, 287
Body Fluids, 57, 192, 222, 223, 238, 284, 291 Bolus, 25, 223 Bolus infusion, 223 Bone Marrow, 4, 63, 139, 166, 212, 221, 223, 234, 252, 259, 262, 263, 295 Bone Resorption, 60, 223, 243 Bowel, 198, 215, 223, 236, 245, 255, 257, 270 Bowel Movement, 198, 223, 236 Bradykinin, 223, 265, 273 Brain Stem, 223, 230, 232 Branch, 16, 125, 205, 223, 269, 271, 277, 284, 288 Breakdown, 223, 236, 244 Bronchi, 223, 241, 242, 288, 290 Bronchial, 223, 250, 288 Buccal, 223, 258 Bullous, 50, 223 Bupivacaine, 223, 257 Buprenorphine, 20, 223 Burns, 110, 165, 223, 224 Burns, Electric, 223, 224 Buspirone, 17, 158, 224 Butorphanol, 125, 224 C Calcification, 219, 224 Calcium, 9, 150, 162, 165, 214, 224, 230, 251, 265, 268, 277, 283, 288 Calcium Carbonate, 150, 162, 224 Calcium channel blocker, 165, 224 Calcium Channel Blockers, 165, 224 Calcium Channels, 224, 268 Calculi, 222, 224, 247 Cannabidiol, 224 Cannabinoids, 147, 224 Cannabinol, 224, 225 Capillary, 157, 223, 225, 293 Capsaicin, 163, 196, 225 Capsular, 148, 225 Capsules, 83, 85, 126, 128, 132, 134, 145, 146, 147, 148, 225, 237, 245 Carbamazepine, 32, 147, 225 Carbohydrate, 225, 233, 246, 247, 273 Carbon Dioxide, 225, 245, 272, 278, 280, 293 Carboxymethylcellulose, 127, 225 Carcinogen, 14, 212, 225, 288 Carcinogenesis, 14, 19, 225 Carcinogenic, 38, 221, 225, 254, 275, 285 Carcinoma, 23, 225 Cardiomyopathy, 29, 225
299
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Acetaminophen
Cardiorespiratory, 213, 225, 261 Cardiovascular, 7, 55, 71, 224, 225, 257, 283 Cardiovascular disease, 7, 225 Carnitine, 69, 225 Carotene, 142, 143, 225 Carrier Proteins, 225, 272 Case report, 3, 51, 53, 64, 75, 85, 226, 229 Case-Control Studies, 23, 226 Caspase, 13, 48, 226 Catalase, 108, 211, 226 Catalyse, 226, 290 Cataract, 106, 124, 225, 226, 241 Catechol, 28, 226 Catecholamine, 226, 237, 271 Cations, 226, 255 Causal, 46, 226 Celecoxib, 55, 56, 60, 61, 71, 79, 83, 128, 226 Cell Cycle, 226, 275 Cell Death, 13, 25, 32, 34, 99, 218, 226, 264 Cell Differentiation, 226, 283, 285 Cell Division, 186, 220, 226, 261, 272 Cell membrane, 221, 224, 225, 226, 235, 284 Cell proliferation, 14, 219, 226, 283 Cell Respiration, 213, 226, 261, 267, 280 Cellobiose, 227 Cellulose, 127, 146, 154, 227, 244, 272 Central Nervous System, 13, 27, 156, 211, 214, 215, 220, 221, 224, 227, 229, 244, 248, 257, 258, 262, 271, 283, 287, 288 Central Nervous System Infections, 227, 248 Centrifugation, 227, 248, 261 Cerebellar, 219, 227, 279 Cerebral, 53, 59, 142, 166, 219, 220, 223, 227, 232, 235, 241, 243, 268, 277 Cerebrospinal, 48, 227, 258, 285 Cerebrospinal fluid, 48, 227, 258, 285 Cerebrovascular, 220, 224, 225, 227, 288 Cerebrum, 227, 291 Cervical, 227, 263, 290 Character, 227, 235 Chemical Warfare, 227, 234 Chemical Warfare Agents, 227, 234 Chemoreceptor, 218, 227, 255 Chemotherapy, 48, 92, 100, 138, 227, 237 Chickenpox, 110, 111, 190, 227 Chlormethiazole, 77, 227 Chlorpheniramine, 112, 147, 227 Chlorpromazine, 165, 228
Cholangitis, 162, 163, 165, 228 Cholecystitis, 162, 228 Cholelithiasis, 162, 228 Cholestasis, 23, 164, 165, 228 Cholesterol, 133, 135, 162, 221, 228, 232, 244, 285, 287 Cholesterol Oxidase, 133, 228 Chondroitin sulfate, 173, 196, 228 Chromatin, 218, 228, 241, 265, 285 Chromosomal, 215, 228 Chromosome, 228, 231, 258, 292 Chronic Disease, 13, 228 Chronic renal, 11, 228, 244, 273, 292 Ciliary, 218, 228 Ciliary processes, 218, 228 Cimetidine, 165, 228 Cinchona, 228, 278 Ciprofloxacin, 165, 228 Citrus, 219, 228 C-kit receptor, 228, 285 Clarithromycin, 17, 229 Cleave, 132, 229 Cleft Palate, 76, 229 Clemastine, 60, 229 Clinical Medicine, 229, 274 Clinical study, 229, 232 Clinical trial, 5, 18, 21, 35, 36, 59, 81, 119, 120, 183, 229, 232, 234, 269, 277, 279 Clonic, 229, 232, 260 Cloning, 39, 44, 56, 222, 229, 258 Coagulation, 61, 222, 229, 249, 272, 289, 294 Coal, 221, 229 Cobalt, 139, 229 Coca, 229 Cocaine, 101, 147, 229 Cochlea, 229, 254 Cochlear, 26, 229, 230 Cochlear Implantation, 26, 229 Cochlear Nerve, 230 Coenzyme, 219, 230 Cofactor, 230, 265, 277, 289 Collagen, 159, 166, 212, 230, 243, 245, 273, 275 Colloidal, 214, 230, 239, 287 Complement, 230, 231, 245, 272 Complementary and alternative medicine, 99, 116, 165, 230 Complementary medicine, 99, 230 Computational Biology, 183, 185, 231 Conception, 38, 231, 243, 274 Concomitant, 5, 76, 231
Index
Cone, 231, 286 Confounding, 23, 38, 231 Congenita, 231, 278 Congestion, 9, 117, 130, 218, 231, 234 Conjugated, 32, 221, 231, 234, 263 Conjugation, 19, 20, 35, 37, 124, 222, 231, 246, 286 Conjunctiva, 231, 253 Connective Tissue, 159, 219, 223, 230, 231, 243, 244, 245, 280, 281 Connective Tissue Cells, 231 Consciousness, 156, 215, 216, 231, 235, 237, 249 Constipation, 198, 218, 231, 270 Constriction, 231, 255, 293, 294 Constriction, Pathologic, 231, 293 Consultation, 193, 231 Consumption, 8, 11, 12, 17, 19, 20, 22, 129, 232, 280 Contamination, 232, 249 Continuous infusion, 31, 232 Continuum, 166, 232 Contraindications, ii, 195, 232 Control group, 12, 18, 34, 232 Controlled clinical trial, 78, 141, 156, 232 Controlled study, 85, 232 Convulsants, 165, 232 Convulsions, 56, 208, 217, 220, 232, 251 Cor, 232 Cornea, 218, 232, 247 Coronary, 225, 232, 233, 261, 263, 270 Coronary heart disease, 225, 232 Coronary Thrombosis, 233, 261, 263 Corpus, 137, 144, 233, 269, 275 Cortex, 77, 107, 219, 233, 243, 279 Corticosteroid, 194, 233 Cortisol, 214, 233 Cortisone, 193, 233, 235 Coumarin, 233 Cranial, 230, 233, 242, 248, 268, 270, 285 Craniocerebral Trauma, 220, 233, 248, 288 Creatine, 11, 233 Creatinine, 11, 233, 256, 292 Creatinine clearance, 11, 233 Cues, 29, 233 Curare, 233, 262 Curative, 42, 106, 233, 265, 288 Cutaneous, 32, 192, 222, 233, 258 Cyclic, 41, 212, 224, 233, 247, 265, 271, 274, 276, 282, 288 Cyclooxygenase Inhibitors, 13, 234 Cyclosporine, 165, 234
301
Cyst, 222, 234 Cysteine, 7, 40, 113, 114, 124, 211, 234, 240, 246, 286 Cystine, 234 Cytochrome, 4, 9, 13, 15, 17, 25, 27, 28, 38, 40, 68, 100, 102, 105, 124, 144, 228, 234 Cytokine, 31, 42, 43, 234, 269 Cytoplasm, 218, 221, 226, 234, 241, 247, 262, 265, 281 Cytoskeleton, 9, 234 Cytostatic, 23, 234 Cytotoxic, 9, 39, 165, 225, 234, 283 Cytotoxicity, 8, 25, 39, 77, 101, 107, 108, 140, 234 D Data Collection, 21, 234 Databases, Bibliographic, 183, 234 Decompensation, 16, 234 Decongestant, 128, 193, 234 Decontamination, 104, 234 Degenerative, 191, 196, 235, 249, 266, 281 Delavirdine, 235, 265 Deletion, 25, 218, 235 Delirium, 190, 217, 235 Dementia, 34, 211, 218, 235 Denaturation, 235, 273 Density, 227, 235, 266, 273 Depolarization, 235, 283 Dermatosis, 50, 235 Detergents, 235, 265 Detoxification, 7, 19, 32, 36, 44, 235, 246 Deuterium, 235, 250 Dexamethasone, 20, 102, 235 Dextromethorphan, 113, 147, 235 Diabetes Mellitus, 7, 235, 246, 248 Diagnostic procedure, 123, 172, 235 Dialyzer, 235, 248 Diarrhea, 192, 208, 236, 239 Diastolic, 236, 251 Diathesis, 24, 236 Diclofenac, 54, 57, 69, 74, 236 Diclofenac Sodium, 69, 236 Didanosine, 85, 236 Dideoxyadenosine, 236 Dietary Fiber, 198, 236 Diffusion, 137, 221, 236, 291 Digestion, 214, 221, 223, 236, 238, 253, 255, 258, 269, 285 Digestive system, 121, 236 Digoxigenin, 147, 236 Dilatation, 165, 216, 236, 275, 293 Dilatation, Pathologic, 236, 293
302
Acetaminophen
Dilation, 153, 223, 236, 293 Dilution, 25, 236 Dimenhydrinate, 125, 236 Dimethyl, 14, 94, 237, 258 Diphenhydramine, 113, 125, 136, 236, 237 Direct, iii, 4, 10, 20, 31, 42, 139, 147, 154, 155, 157, 175, 229, 237, 268, 278, 279, 287 Discoid, 192, 237 Disinfectant, 237, 242 Disorientation, 235, 237 Disposition, 10, 16, 17, 20, 36, 57, 64, 68, 103, 105, 237 Dissociation, 213, 237, 255 Distal, 237, 239, 277 Disulfides, 33, 237 Dithionite, 137, 237 Diuresis, 224, 237, 288 Diuretic, 237, 244, 284 Dopa, 165, 237, 257 Dopamine, 218, 228, 229, 237, 257, 271 Dosage Forms, 126, 127, 128, 136, 137, 143, 148, 154, 155, 156, 237 Dose-dependent, 5, 144, 164, 238, 295 Drug Interactions, 10, 15, 26, 27, 40, 177, 238 Drug Tolerance, 238, 289 Drug Toxicity, 32, 238 Duct, 215, 228, 238, 242, 268, 281 Duodenum, 139, 221, 238, 240, 245, 285 Dura mater, 238, 260, 267 Dyes, 26, 221, 238, 265, 286 Dysmenorrhea, 55, 110, 238 Dyspepsia, 198, 238, 253 Dysplasia, 187, 238 Dyspnea, 234, 238, 268 Dystrophy, 186, 238 E Edema, 53, 166, 234, 238, 244, 249, 292 Effector, 211, 230, 238, 264, 271 Effector cell, 238, 264 Eicosanoids, 41, 234, 238 Ejaculation, 238, 282 Elasticity, 158, 174, 219, 238 Elastin, 230, 238 Elective, 76, 238 Electrocoagulation, 229, 239 Electrode, 133, 157, 216, 239 Electrolysis, 216, 226, 239 Electrolyte, 233, 235, 239, 248, 256, 261, 274, 284, 292 Electrons, 217, 221, 239, 255, 267, 278 Electrophoresis, 26, 239
Electroplating, 226, 239, 286 Emaciation, 211, 239 Emboli, 239, 294 Embolism, 239, 278, 294 Embolization, 239, 294 Embryo, 222, 226, 239, 253, 274, 285 Embryo Transfer, 239, 274 Embryogenesis, 239, 285 Emesis, 104, 106, 208, 239 Emetic, 239, 255 Emetine, 239, 255 Emollient, 239, 247, 266 Emulsions, 128, 147, 239 Encapsulated, 135, 149, 240 Encephalitis, 190, 240 Encephalitis, Viral, 240 Encephalopathy, 64, 166, 240 Endocrine Glands, 240, 268 Endometrial, 47, 240 Endometrium, 240, 260 Endopeptidases, 240, 276 Endoscopic, 219, 240, 261 Endothelial cell, 9, 13, 223, 240, 289 Endothelium, 240, 265 Endothelium-derived, 240, 265 Endotoxemia, 14, 47, 240 Endotoxin, 13, 61, 240, 291 End-stage renal, 4, 228, 240, 273 Environmental Exposure, 240, 266 Environmental Health, 20, 95, 109, 182, 184, 240 Environmental Pollutants, 19, 240 Enzymatic, 29, 62, 146, 157, 224, 225, 230, 236, 241, 250, 273 Enzyme Induction, 124, 241 Enzyme Inhibitors, 241, 272 Eosinophilia, 241, 242 Eosinophils, 241, 247, 257 Epidemic, 140, 241, 285 Epidemiological, 14, 41, 241 Epigastric, 241, 268 Epinephrine, 213, 237, 241, 265, 291 Epithelial, 159, 212, 221, 241 Erectile, 241, 269 Ergot, 141, 176, 241, 281 Ergot Alkaloids, 141, 241 Erythrocytes, 7, 102, 216, 220, 222, 223, 241, 268, 279 Erythromycin, 17, 165, 229, 241 Esophagus, 198, 236, 241, 248, 271, 279, 285, 293 Essential Tremor, 186, 241
Index
Estradiol, 37, 41, 241 Estrogen, 37, 241, 282, 287 Ethanol, 8, 23, 28, 62, 81, 93, 242 Ethmoid, 242, 268 Eukaryotic Cells, 242, 253 Evacuation, 231, 242, 245, 257 Excipient, 92, 150, 242 Excitability, 242, 263, 278 Excrete, 218, 242, 256, 280 Exercise Therapy, 18, 166, 242 Exocrine, 242, 268 Exogenous, 10, 19, 29, 37, 157, 213, 222, 242, 246, 276, 286 Expectorant, 128, 242 Extracellular, 231, 242, 243, 284, 288 Extracellular Matrix, 231, 242, 243 Extracorporeal, 86, 242, 248 Extraction, 57, 242 Extremity, 197, 242 Exudate, 242, 266 F Family Planning, 183, 242 Fasciitis, 194, 242 Fat, 218, 221, 223, 225, 232, 233, 239, 243, 256, 258, 273, 281, 284, 287, 291 Fatigue, 110, 130, 141, 243, 248 Fatty acids, 150, 214, 238, 243, 246, 275 Fatty Liver, 51, 162, 163, 243 Febrile, 52, 55, 56, 243, 278 Feces, 231, 243 Ferritin, 139, 243 Fertilization in Vitro, 243, 274 Fertilizers, 151, 243, 286 Fetus, 20, 243, 272, 274, 285, 292 Fibrin, 222, 243, 270, 289 Fibrinogen, 243, 272, 277, 289 Fibroblasts, 231, 242, 243 Fibrosarcoma, 242, 243 Fibrosis, 165, 187, 243, 249, 282 Fissure, 229, 243 Flatus, 243, 244 Fluorescence, 16, 243 Flurbiprofen, 16, 243 Fluvoxamine, 16, 243 Fold, 8, 37, 243, 244 Follicles, 244, 254 Foot Bones, 197, 244 Forearm, 223, 242, 244 Free Radical Scavengers, 244, 288 Fructose, 244, 247 Fulminant Hepatic Failure, 23, 53, 56, 61, 62, 79, 86, 165, 244
303
Fungi, 217, 219, 231, 244, 247, 261, 295 Fungus, 241, 244, 281 Furosemide, 34, 244 G GABA, 227, 244, 271, 283, 292 Galactosemia, 163, 244 Gallbladder, 211, 221, 228, 236, 244 Gallstones, 163, 221, 228, 244 Gamma-interferon, 43, 244 Ganglia, 211, 220, 244, 264, 270 Gas, 89, 225, 236, 243, 244, 250, 253, 265, 287, 293 Gas exchange, 244, 293 Gasoline, 221, 245 Gastric, 88, 137, 208, 220, 225, 228, 237, 245, 248, 250, 255, 269, 270, 279, 285 Gastric Acid, 228, 245 Gastric Emptying, 88, 245 Gastric Juices, 245, 269 Gastric Mucosa, 245, 255, 270 Gastrin, 228, 245, 250 Gastrointestinal, 13, 43, 45, 46, 49, 55, 63, 77, 78, 84, 126, 132, 149, 162, 164, 193, 223, 228, 241, 242, 245, 257, 279, 283, 286, 291 Gastrointestinal tract, 13, 132, 164, 242, 245, 257, 283, 291 Gastrointestinal Transit, 126, 245 Gelatin, 83, 132, 133, 134, 136, 145, 148, 245, 247, 286, 288 Gels, 146, 176, 245 Gene, 8, 13, 19, 21, 23, 29, 30, 39, 43, 187, 188, 196, 214, 222, 241, 245, 258, 266 Gene Expression, 13, 187, 245 Genetic Engineering, 222, 229, 245 Genetic testing, 245, 273 Genetics, 166, 192, 197, 198, 231, 245, 271 Genital, 110, 140, 228, 245 Genotype, 19, 21, 37, 245, 271 Geriatric, 128, 245 Gestation, 20, 39, 245, 272, 285 Ginseng, 114, 245 Gland, 213, 233, 245, 268, 272, 276, 282, 285, 289 Glomerular, 246, 256, 280 Glucocorticoid, 235, 246 Gluconeogenesis, 139, 246 Glucose Intolerance, 235, 246 Glucose tolerance, 7, 246 Glucose Tolerance Test, 246 Glucuronate, 139, 246 Glucuronic Acid, 18, 124, 246
304
Acetaminophen
Glucuronides, 246 Glucuronosyltransferase, 30, 67, 246 Glutamate, 20, 139, 219, 235, 246, 271 Glutamate-Cysteine Ligase, 20, 246 Glutathione Peroxidase, 13, 49, 246, 282 Glycerol, 41, 246 Glycine, 221, 227, 247, 282 Glycogen, 247 Glycols, 247, 251 Glycoprotein, 243, 247, 262, 271, 289, 291 Glycosaminoglycan, 228, 247 Glycoside, 135, 247, 281 Glycosylation, 135, 247 Gonadal, 247, 285 Gonadotropin, 41, 247 Gout, 197, 247 Governing Board, 247, 274 Grade, 150, 247 Gram-negative, 240, 247 Granulocytes, 247, 283, 294 Granulosa Cells, 247, 254 Grasses, 247 Guanylate Cyclase, 247, 265 H Haematemesis, 239, 248 Half-Life, 84, 248 Haloperidol, 165, 248 Haptens, 213, 248 Headache, 55, 60, 65, 68, 87, 112, 125, 130, 141, 155, 174, 176, 196, 224, 248, 251, 253 Headache Disorders, 248 Heart attack, 225, 248 Heart failure, 162, 248 Heartbeat, 248, 286 Heartburn, 198, 248, 253 Hematocrit, 25, 222, 248 Hematuria, 167, 248 Heme, 38, 139, 221, 234, 248, 263, 274 Hemochromatosis, 138, 162, 163, 248 Hemodialysis, 64, 138, 224, 235, 248, 256, 257, 291 Hemofiltration, 68, 248, 291 Hemoglobin, 139, 216, 222, 241, 248, 249, 274, 288 Hemoglobinuria, 186, 249 Hemolytic, 64, 138, 242, 249, 288 Hemorrhage, 233, 239, 248, 249, 272, 286 Hemorrhoids, 198, 249 Hemosiderin, 139, 249 Hemostasis, 249, 283 Hepatic, 4, 9, 10, 16, 17, 23, 25, 26, 28, 29, 31, 33, 35, 36, 42, 58, 63, 64, 78, 82, 83,
94, 101, 106, 117, 130, 138, 139, 144, 162, 165, 214, 235, 239, 246, 249, 258 Hepatic Encephalopathy, 17, 162, 165, 249 Hepatic Veins, 249 Hepatic Veno-Occlusive Disease, 63, 249 Hepatitis, 4, 16, 17, 53, 85, 86, 111, 162, 163, 164, 165, 166, 192, 195, 244, 249, 270, 294 Hepatitis A, 16, 85, 86, 249 Hepatitis, Chronic, 16, 249 Hepatobiliary, 10, 26, 249 Hepatoblastoma, 100, 249 Hepatocellular, 25, 28, 31, 74, 165, 249 Hepatocellular carcinoma, 165, 249 Hepatocyte, 10, 23, 28, 42, 78, 101, 228, 249 Hepatoma, 48, 249 Hepatorenal Syndrome, 162, 249 Hepatotoxic, 9, 15, 23, 31, 57, 62, 144, 249 Hepatovirus, 249 Herbicide, 249, 269 Hereditary, 138, 163, 247, 250, 264, 270, 280, 288 Heredity, 245, 250 Heterodimers, 30, 250 Heterogeneity, 213, 250 Heterogenic, 250 Heterogenous, 30, 250 Heterotropic, 27, 250 Hiccup, 228, 250 Histamine, 217, 218, 227, 228, 229, 237, 250, 258, 261, 275, 279 Histidine, 39, 250 Homeostasis, 8, 250 Homogeneous, 219, 232, 250, 271 Homologous, 214, 250, 287 Hormonal, 19, 220, 233, 250 Hormone, 23, 29, 149, 196, 233, 238, 241, 245, 250, 253, 254, 255, 275, 281, 282, 283, 288, 289 Hormone Replacement Therapy, 23, 196, 250 Host, 220, 250, 252, 257, 281, 292, 294 Hybrid, 30, 250, 281 Hydrocodone, 26, 54, 56, 60, 76, 250 Hydrogen Peroxide, 58, 146, 157, 226, 228, 246, 250, 258 Hydrolysis, 19, 135, 219, 222, 227, 236, 250, 271, 272, 273 Hydrophobic, 151, 235, 251 Hydroxides, 251 Hydroxyl Radical, 36, 251 Hydroxylysine, 230, 251
Index
Hydroxyproline, 230, 251 Hydroxysteroids, 228, 251 Hyperbilirubinemia, 251, 256 Hypercalcemia, 214, 251 Hyperglycemia, 73, 251 Hyperplasia, 31, 251 Hypersensitivity, 48, 73, 82, 172, 215, 237, 251, 257, 281 Hypertension, 17, 46, 162, 170, 219, 224, 225, 232, 248, 251, 292 Hypertension, Portal, 162, 251 Hyperthermia, 165, 251 Hypertrophy, 12, 221, 232, 251 Hyperuricemia, 247, 251 Hypnotic, 174, 220, 237, 251, 258, 261 Hypoglycaemia, 235, 251 Hypoglycemia, 29, 144, 166, 251 Hypoglycemic, 165, 251 Hypoglycemic Agents, 165, 251 Hypothermia, 117, 165, 251 Hypoxanthine, 251, 294 Hypoxia, 235, 252, 288 I Iatrogenic, 23, 252 Id, 58, 96, 109, 199, 204, 206, 252 Idiopathic, 66, 252 Imaging procedures, 252, 290 Imidazole, 222, 250, 252, 279 Imipramine, 20, 252 Immune response, 29, 32, 41, 213, 217, 233, 248, 252, 286, 292, 294 Immune Sera, 252 Immune system, 220, 238, 252, 257, 259, 271, 292, 294 Immunity, 211, 214, 252, 290 Immunization, 194, 195, 252 Immunoassay, 147, 252 Immunodeficiency, 140, 186, 211, 252 Immunoglobulins, 252, 272 Immunologic, 252, 269, 295 Immunology, 60, 73, 78, 82, 212, 213, 252 Impairment, 9, 78, 219, 228, 235, 252, 260 Implantation, 231, 252 Impotence, 241, 253, 268 In situ, 27, 253 In Situ Hybridization, 27, 253 In vivo, 7, 10, 13, 14, 15, 17, 24, 25, 27, 28, 31, 32, 33, 41, 56, 75, 99, 139, 140, 236, 253, 267, 289 Incision, 253, 255, 276 Incubated, 25, 253 Incubation, 25, 253
305
Indicative, 157, 164, 253, 269, 293 Indigestion, 130, 253 Indomethacin, 137, 145, 253, 256, 290 Induction, 4, 9, 14, 15, 19, 20, 28, 31, 45, 124, 216, 218, 253 Infarction, 253 Influenza, 111, 190, 253 Infusion, 253, 290 Ingestion, 3, 4, 5, 9, 15, 28, 35, 70, 75, 86, 87, 104, 132, 143, 246, 253, 273, 288 Inhalation, 153, 213, 250, 253, 273 Inhibin, 41, 253 Initiation, 7, 14, 32, 94, 161, 254, 258, 290 Inner ear, 27, 254, 293 Inorganic, 150, 237, 251, 254, 262, 271, 286 Insecticides, 254, 271, 295 Insight, 14, 26, 43, 254 Insomnia, 174, 254, 267 Insulin, 81, 157, 246, 254, 256 Insulin-dependent diabetes mellitus, 254 Intensive Care, 59, 166, 254 Interferon, 244, 254 Interindividual, 32, 38, 67, 254 Interleukin-1, 47, 254 Interleukin-2, 254 Intermittent, 166, 254, 258, 270 Internal Medicine, 5, 6, 46, 51, 59, 60, 68, 69, 82, 83, 89, 92, 254, 281 Interstitial, 157, 254, 280 Intervertebral, 254, 258 Intervertebral Disk Displacement, 254, 258 Intestinal, 10, 16, 17, 139, 143, 225, 246, 255, 259 Intestine, 139, 221, 223, 245, 255, 257 Intoxication, 48, 106, 129, 235, 255, 294 Intracellular, 9, 13, 14, 43, 224, 253, 255, 265, 274, 276, 279, 282, 283 Intrahepatic, 10, 17, 255 Intravenous, 16, 59, 72, 83, 89, 119, 253, 255 Intrinsic, 213, 255 Invasive, 252, 255, 259 Involuntary, 220, 241, 255, 263, 284, 295 Iodine, 255, 261 Ion Channels, 255, 264 Ionization, 80, 255 Ions, 138, 220, 224, 237, 239, 250, 255, 277, 284 Ipecac, 103, 194, 239, 255 Irrigation, 163, 255 Ischemia, 220, 255
306
Acetaminophen
Ischemic stroke, 44, 59, 76, 84, 171, 255 Isoenzyme, 30, 255 Isoniazid, 28, 165, 255 Itraconazole, 16, 117, 256 J Jaundice, 162, 163, 164, 166, 192, 249, 251, 256 Joint, 43, 150, 152, 163, 191, 195, 196, 219, 228, 256, 266, 285, 287 K Kava, 44, 52, 101, 256 Kb, 182, 256 Keto, 256, 290 Ketone Bodies, 29, 211, 256 Ketoprofen, 68, 72, 197, 256 Ketorolac, 46, 68, 72, 256 Ketorolac Tromethamine, 46, 256 Kidney Disease, 51, 119, 121, 161, 182, 187, 191, 256 Kidney Failure, 4, 191, 240, 256 Kidney Failure, Acute, 256 Kidney Failure, Chronic, 256 Kidney stone, 257, 280, 292 Kinetic, 16, 27, 30, 38, 257 L Labyrinth, 229, 254, 257, 282, 293 Large Intestine, 236, 255, 257, 279, 284 Latency, 23, 257 Lavage, 208, 257 Laxative, 225, 257, 284 Lens, 218, 225, 226, 231, 257, 280 Lesion, 9, 222, 257, 291 Lethal, 21, 34, 220, 257 Leukemia, 140, 186, 257 Leukocytes, 153, 221, 222, 223, 241, 247, 253, 257, 262, 265, 268, 270, 291 Leukopenia, 257, 295 Leukotrienes, 218, 238, 257 Levo, 237, 257, 275 Levodopa, 237, 257 Levorphanol, 235, 257 Library Services, 204, 257 Lidocaine, 67, 257 Ligament, 257, 276, 285 Ligands, 16, 258 Ligase, 258, 278 Linkage, 39, 40, 227, 258, 270 Lipid, 41, 107, 159, 219, 240, 246, 254, 256, 258, 261, 267 Lipid Peroxidation, 107, 258, 267 Liver cancer, 163, 165, 258 Liver Cirrhosis, 249, 258
Liver Neoplasms, 258, 293 Liver Regeneration, 24, 258 Liver Transplantation, 5, 16, 23, 51, 53, 63, 81, 86, 162, 163, 166, 258 Loading dose, 171, 258 Localized, 39, 153, 166, 215, 240, 253, 258, 263, 272, 282, 291, 292 Long-Term Care, 43, 258 Loperamide, 58, 258 Lorazepam, 33, 258 Low Back Pain, 54, 55, 59, 111, 258 Lumbar, 72, 141, 220, 254, 258, 285 Lumbar puncture, 141, 258, 285 Lupus, 192, 197, 258 Lymph, 227, 240, 258, 259 Lymphatic, 240, 253, 258, 259, 273, 285, 289 Lymphocyte, 211, 217, 259 Lymphocyte Count, 211, 259 Lymphoid, 217, 259 Lymphoma, 186, 259 Lysine, 39, 251, 259 M Macrolides, 16, 259 Macrophage, 31, 45, 66, 254, 259 Magnetic Resonance Imaging, 12, 259 Malabsorption, 186, 259 Malignant, 186, 211, 212, 217, 219, 242, 258, 259, 264, 275 Malnutrition, 35, 130, 214, 220, 259, 263 Mammary, 259, 287 Manifest, 130, 157, 259 Man-made, 226, 259 Maxillary, 259, 268 Medial, 219, 242, 244, 259, 285 Mediate, 41, 230, 237, 259, 279 Mediator, 94, 237, 254, 259, 283 Medical Records, 5, 39, 259 Medicament, 136, 147, 259, 286 MEDLINE, 183, 185, 187, 259 Medullary, 235, 259 Melanin, 260, 271, 291 Melanocytes, 260 Melanoma, 186, 260 Memory, 235, 260 Meninges, 227, 233, 238, 260 Meningitis, 190, 256, 260, 272 Menopause, 260, 274 Menstrual Cycle, 41, 260, 275 Menstruation, 86, 238, 260 Mental Disorders, 121, 260, 272, 277
Index
Mental Health, iv, 5, 121, 182, 184, 260, 277 Mentors, 32, 260 Meperidine, 53, 260 Mephenytoin, 16, 260 Meta-Analysis, 54, 63, 260 Metabolic disorder, 247, 260 Metabolite, 4, 8, 10, 18, 19, 20, 25, 28, 32, 35, 36, 39, 40, 55, 62, 78, 124, 222, 236, 237, 260 Metalloporphyrins, 105, 260 Metatarsal Bones, 244, 261 Metatarsus, 244, 261 Methacrylate, 126, 261 Methapyrilene, 125, 261 Methimazole, 105, 261 Methionine, 93, 94, 114, 124, 237, 261, 286 MI, 15, 126, 135, 151, 163, 196, 209, 261 Microbe, 261, 290 Microorganism, 230, 261, 269, 294 Microscopy, 10, 92, 261 Microsomal, 3, 26, 40, 261 Midazolam, 16, 17, 27, 261 Migration, 45, 66, 153, 261 Milk Thistle, 114, 261, 283 Mineralocorticoids, 213, 233, 261 Mitochondria, 25, 261 Mitochondrial Swelling, 261, 264 Mitosis, 218, 261 Modeling, 36, 262 Modification, 40, 236, 245, 262, 278, 295 Monitor, 27, 192, 233, 262, 265 Monocytes, 254, 257, 262 Mononuclear, 242, 262, 291 Morphine, 16, 20, 33, 71, 156, 158, 223, 230, 260, 262, 263, 266 Morphological, 27, 239, 244, 260, 262 Morphology, 226, 262 Motility, 253, 262, 283 Motion Sickness, 237, 262, 263, 275 Motor nerve, 262 Mucins, 262, 281 Mucolytic, 211, 262 Mucosa, 245, 258, 262, 263 Mucus, 242, 262 Multidrug resistance, 262, 271 Muscle Fibers, 262 Muscle relaxant, 173, 216, 262, 287 Muscle tension, 262 Muscular Atrophy, 186, 262 Muscular Dystrophies, 238, 263 Mutagenesis, 15, 27, 28, 105, 263
307
Mutagens, 263 Myalgia, 253, 263 Mydriatic, 236, 263 Myelogenous, 263 Myocardial infarction, 46, 233, 261, 263, 294 Myocardium, 261, 263 Myoglobin, 139, 263, 274 Myopathy, 29, 263 Myotonia, 263, 278 Myotonic Dystrophy, 186, 263 N Narcosis, 263 Narcotic, 73, 130, 177, 192, 211, 224, 250, 257, 260, 262, 263, 267, 275, 290 Nasal Cavity, 263, 268 Nasal Mucosa, 253, 263 Nausea, 18, 131, 141, 155, 192, 198, 208, 217, 218, 237, 253, 263, 268, 292 NCI, 1, 120, 181, 263 Neck Pain, 174, 263 Necrosis, 4, 9, 21, 23, 25, 28, 33, 35, 36, 138, 144, 165, 218, 242, 249, 253, 261, 263, 280 Nelfinavir, 16, 264 Neonatal, 33, 141, 264 Neoplasia, 186, 264 Neoplasms, 211, 217, 264, 288 Neoplastic, 259, 264 Nephropathy, 4, 11, 138, 256, 264 Nephrosis, 249, 264 Nephrotoxic, 15, 25, 264 Nerve, 213, 216, 219, 230, 259, 262, 264, 267, 274, 275, 280, 282, 285, 291 Networks, 162, 264 Neural, 159, 264, 284 Neurodegenerative Diseases, 41, 140, 220, 264 Neurogenic, 264, 292 Neurons, 229, 230, 244, 257, 262, 264, 287 Neuropathy, 162, 264, 270 Neurotoxicity, 235, 264 Neurotransmitters, 37, 264 Neutrons, 214, 264, 278 Neutrophils, 247, 257, 265 Nevirapine, 265 Niacin, 164, 165, 265, 291 Nickel, 145, 265 Nifedipine, 93, 265 Nitric Oxide, 10, 31, 36, 93, 265 Nitrogen, 13, 33, 84, 214, 216, 256, 260, 265, 291 Non-nucleoside, 141, 235, 265
308
Acetaminophen
Nonoxynol, 140, 265 Norepinephrine, 213, 237, 265 Nuclear, 26, 29, 47, 220, 229, 231, 239, 242, 259, 264, 265, 275 Nuclei, 24, 214, 230, 231, 239, 245, 259, 261, 264, 265, 277 Nucleic acid, 236, 251, 253, 263, 265, 278, 295 Nucleus, 218, 220, 221, 228, 230, 233, 234, 235, 241, 242, 254, 262, 265, 266, 277, 286, 288 O Obstetrics, 66, 241, 266 Occult, 62, 147, 266 Odds Ratio, 5, 266 Ointments, 197, 237, 266 Oliguria, 256, 266 Oncogene, 186, 266, 285 Oncology, 108, 165, 266 Opacity, 226, 235, 266 Ophthalmic, 124, 266 Opium, 104, 156, 262, 266, 268 Opportunistic Infections, 211, 266 Orphenadrine, 153, 266 Osmotic, 214, 261, 266 Osteoporosis, 214, 266 Osteotomy, 196, 266 Outpatient, 22, 85, 266 Ovary, 241, 266, 267 Overdosage, 71, 84, 144, 267 Overdose, 3, 4, 5, 31, 35, 42, 45, 47, 49, 50, 52, 57, 59, 61, 64, 66, 70, 73, 74, 75, 78, 79, 80, 81, 83, 86, 87, 89, 92, 94, 101, 103, 132, 138, 144, 166, 170, 171, 193, 207, 232, 244, 267 Ovum, 245, 267, 275, 295 Oxaloacetate, 219, 267 Oxazepam, 105, 267 Oxidants, 7, 34, 267 Oxidation, 9, 28, 29, 33, 41, 58, 100, 105, 125, 159, 211, 217, 222, 228, 234, 246, 258, 261, 267 Oxidation-Reduction, 222, 267 Oxidative metabolism, 15, 213, 257, 267 Oxidative Stress, 7, 9, 13, 21, 44, 100, 267 Oxides, 145, 267 Oxycodone, 11, 54, 59, 77, 82, 86, 171, 267 Oxygenation, 41, 267 P Pachymeningitis, 260, 267 Paediatric, 52, 57, 74, 82, 267 Pain Threshold, 53, 158, 267
Palate, 229, 267 Palladium, 145, 268 Palliative, 268, 288 Pancreas, 164, 211, 222, 236, 248, 254, 268, 291 Pancreatic, 186, 225, 244, 268 Pancreatic cancer, 186, 268 Pancreatitis, 73, 85, 100, 129, 268 Pancytopenia, 4, 73, 268 Panic, 243, 252, 268 Panic Disorder, 243, 252, 268 Papaverine, 156, 266, 268 Paranasal Sinuses, 59, 268 Parathyroid, 162, 268, 288 Parathyroid Glands, 162, 268 Parathyroid hormone, 268 Parkinsonism, 218, 257, 266, 269 Paroxysmal, 186, 220, 248, 269 Particle, 137, 259, 269, 290 Patella, 166, 269 Pathogen, 253, 269 Pathogenesis, 6, 30, 92, 163, 269 Pathologic, 23, 158, 211, 218, 222, 232, 251, 269, 277, 280 Pathologic Processes, 218, 269 Pathologies, 165, 269 Pathophysiology, 9, 20, 41, 164, 269 Patient Compliance, 137, 269 Patient Education, 163, 190, 192, 198, 202, 204, 209, 269 Patient Selection, 195, 269 Pediatrics, 4, 5, 19, 29, 31, 33, 35, 49, 53, 55, 56, 62, 66, 74, 75, 76, 84, 94, 133, 193, 194, 269 Pelvic, 269, 276 Penis, 140, 238, 269 Pentachlorophenol, 93, 269 Pentoxifylline, 36, 269 Pepsin, 228, 269, 270 Pepsin A, 228, 269, 270 Peptic, 171, 269, 270 Peptic Ulcer, 171, 270 Peptide, 229, 240, 269, 270, 273, 276, 277 Peptide Chain Elongation, 229, 270 Perception, 156, 231, 270 Perfusion, 244, 252, 270, 289 Perhexiline, 165, 270 Perineal, 44, 65, 270 Perineum, 270 Periodontal disease, 243, 270 Periodontitis, 46, 270 Peripheral Nervous System, 264, 270, 286
Index
Peritoneal, 4, 164, 219, 270 Peritoneal Cavity, 219, 270 Peritoneal Dialysis, 4, 270 Peritoneum, 270 Peritonitis, 162, 270 Peroxidase, 132, 258, 261, 270 Peroxide, 36, 270 Pesticides, 151, 254, 270 P-Glycoprotein, 17, 271 Phagocyte, 267, 271 Pharmaceutical Preparations, 26, 150, 227, 242, 245, 271, 275 Pharmaceutical Solutions, 238, 271 Pharmacist, 193, 271 Pharmacodynamic, 36, 67, 135, 271 Pharmacogenetics, 37, 38, 43, 94, 271 Pharmacokinetic, 7, 15, 16, 20, 36, 67, 74, 77, 106, 271 Pharmacologic, 10, 13, 20, 42, 132, 163, 216, 220, 248, 271, 289, 290, 292 Pharmacotherapy, 36, 48, 54, 58, 62, 64, 65, 67, 70, 75, 84, 89, 271 Pharynx, 253, 263, 271 Phenobarbital, 20, 26, 100, 271 Phenotype, 21, 29, 37, 271 Phenyl, 39, 260, 271 Phenylacetate, 139, 271 Phenylalanine, 269, 271, 291 Phosphates, 150, 271 Phosphodiesterase, 269, 271 Phospholipases, 40, 271, 272, 283 Phospholipases A, 40, 272 Phosphorus, 165, 224, 268, 272 Photocoagulation, 229, 272 Photophobia, 131, 141, 155, 272 Physical Examination, 166, 192, 272 Physical Fitness, 242, 272 Physical Therapy, 18, 272 Physiologic, 10, 23, 213, 222, 237, 248, 260, 272, 275, 279, 280 Physiology, 41, 58, 93, 212, 272 Pigment, 221, 260, 263, 272 Pilot study, 10, 60, 76, 272 Pituitary Gland, 233, 272 Placebo Effect, 18, 272 Placenta, 241, 272, 275 Plants, 214, 219, 225, 228, 229, 245, 246, 247, 249, 262, 265, 272, 273, 278, 281, 290 Plasma cells, 217, 272 Plasma protein, 153, 214, 272, 277 Platelet Activation, 273, 283 Platelet Aggregation, 14, 265, 269, 273, 289
309
Platelets, 14, 37, 265, 268, 273, 289 Platinum, 145, 268, 273 Plexus, 72, 273 Polycystic, 187, 273 Polyethylene, 134, 273 Polymerase, 13, 27, 218, 273 Polymerase Chain Reaction, 27, 273 Polymers, 151, 273, 277 Polypeptide, 215, 230, 243, 263, 269, 273, 277, 288, 295 Polysaccharide, 217, 227, 247, 273 Polyunsaturated fat, 9, 273, 289 Porphyrins, 260, 274 Portal Vein, 251, 274 Portosystemic Shunt, 17, 274 Posterior, 215, 219, 220, 263, 267, 268, 274, 285 Postmenopausal, 23, 214, 266, 274 Postoperative, 15, 22, 54, 59, 65, 68, 71, 72, 76, 78, 80, 162, 164, 256, 260, 274 Postoperative Period, 15, 164, 274 Postsynaptic, 274, 283, 287 Post-translational, 40, 274 Potassium, 105, 134, 261, 274, 278 Potentiate, 227, 274 Potentiation, 9, 75, 274, 283 Practice Guidelines, 184, 274 Precursor, 7, 218, 237, 238, 241, 257, 265, 271, 274, 277, 291 Pregnancy Outcome, 39, 274 Premedication, 83, 274 Prenatal, 38, 239, 274 Prevalence, 7, 147, 163, 266, 274 Primary Biliary Cirrhosis, 162, 163, 275 Probe, 18, 30, 51, 275 Procaine, 257, 275 Progeny, 231, 275 Progesterone, 275, 285 Progression, 7, 9, 196, 216, 275 Progressive, 16, 219, 226, 228, 235, 238, 247, 256, 263, 264, 266, 273, 275, 280 Proliferating Cell Nuclear Antigen, 24, 275 Proline, 230, 251, 275 Promethazine, 228, 275 Promoter, 26, 43, 275 Prophylaxis, 14, 58, 164, 218, 275, 280, 292, 294 Proportional, 39, 275 Propoxyphene, 26, 275 Propylene Glycol, 134, 146, 275 Prospective study, 95, 275
310
Acetaminophen
Prostaglandin, 13, 44, 57, 149, 234, 275, 276, 289 Prostaglandin-Endoperoxide Synthase, 234, 276 Prostaglandins A, 149, 253, 275, 276 Prostaglandins D, 276 Prostate, 167, 186, 221, 222, 276, 291 Prostatectomy, 167, 276 Prostatic Hyperplasia, 276 Protease, 16, 141, 264, 276, 281 Protease Inhibitors, 16, 141, 276 Protective Agents, 224, 276 Protein Binding, 276, 289 Protein C, 27, 214, 215, 243, 276, 292 Protein Conformation, 27, 215, 276 Protein S, 12, 40, 58, 187, 218, 222, 229, 239, 241, 276, 277, 281, 288 Prothrombin, 24, 277, 289 Prothrombin Time, 24, 277 Protocol, 21, 45, 85, 277 Protons, 214, 250, 277, 278 Protozoa, 231, 261, 277 Proximal, 43, 237, 263, 277 Pruritus, 229, 237, 275, 277, 292 Psoriasis, 277, 280 Psychiatry, 277, 286 Psychogenic, 277, 292 Psychomotor, 225, 235, 277, 278 Psychotherapy, 166, 277, 279 Public Health, 13, 39, 95, 184, 277 Public Policy, 183, 277 Publishing, 44, 277 Pulmonary, 222, 232, 244, 248, 256, 257, 278, 287, 293, 294 Pulmonary Artery, 222, 278, 293 Pulmonary Edema, 256, 278 Pulmonary Embolism, 278, 294 Pulse, 208, 262, 278 Pupil, 232, 236, 263, 278 Purifying, 137, 235, 278 Purines, 278, 282, 294 Pyrexia, 13, 278 Pyridoxal, 278, 290 Pyruvate Carboxylase, 25, 278 Q Quality of Life, 150, 278, 286 Quaternary, 276, 278 Quinidine, 147, 165, 228, 278 Quinine, 165, 228, 278 R Race, 5, 237, 261, 278 Radiation, 23, 240, 243, 251, 259, 278, 295
Radioactive, 139, 234, 248, 250, 252, 255, 259, 265, 278 Radioisotope, 278, 290 Randomized, 18, 19, 22, 34, 44, 47, 54, 59, 60, 61, 65, 69, 77, 78, 81, 85, 86, 87, 119, 238, 279 Randomized clinical trial, 22, 34, 279 Ranitidine, 165, 279 Reactive Oxygen Species, 6, 9, 13, 20, 153, 279 Reagent, 132, 157, 279 Reassurance, 166, 279 Receptor, 26, 29, 42, 70, 142, 151, 156, 212, 217, 224, 227, 229, 231, 235, 237, 271, 279, 283 Receptors, Serotonin, 279, 283 Recombinant, 37, 279, 293 Recombination, 231, 279 Rectal, 52, 55, 64, 65, 67, 76, 78, 79, 85, 129, 198, 279 Rectum, 140, 198, 218, 223, 236, 243, 244, 257, 276, 279, 286 Red blood cells, 25, 241, 249, 279, 281, 284 Red Nucleus, 219, 279 Refer, 1, 223, 230, 244, 265, 279, 293 Reflux, 130, 198, 279 Refraction, 279, 284 Regeneration, 30, 42, 279 Regimen, 149, 238, 269, 271, 272, 279 Regurgitation, 248, 280 Relaxant, 268, 280 Relaxation Techniques, 196, 280 Renal failure, 4, 50, 68, 166, 235, 249, 280 Renal tubular, 144, 280 Reproduction Techniques, 274, 280 Resection, 24, 42, 196, 280, 291 Resolving, 35, 62, 280 Resorption, 280 Respiration, 218, 225, 227, 232, 233, 262, 280 Respiratory Paralysis, 211, 280 Restoration, 272, 280 Retina, 257, 280, 281 Retinoblastoma, 186, 280 Retinoids, 165, 280 Retropubic, 276, 280 Retrospective, 11, 63, 280 Rhabdomyolysis, 50, 73, 280 Rheology, 269, 280 Rheumatic Diseases, 166, 280 Rheumatism, 49, 55, 57, 62, 63, 76, 88, 252, 281
Index
Rheumatoid, 76, 77, 138, 196, 197, 256, 267, 281 Rheumatoid arthritis, 76, 77, 138, 196, 197, 256, 281 Rheumatology, 12, 18, 76, 77, 80, 86, 88, 195, 281 Rhinitis, 227, 229, 281 Riboflavin, 93, 281 Ribose, 212, 281 Ribosome, 281, 291 Risk factor, 4, 5, 8, 53, 54, 65, 74, 78, 163, 164, 196, 198, 275, 281 Ristocetin, 281, 293 Ritonavir, 16, 281 Rod, 220, 240, 281 Rodenticides, 271, 281 Rye, 241, 281 S Salicylate, 14, 41, 281 Salicylic, 142, 281 Saline, 193, 281 Saliva, 65, 281 Salivary, 88, 236, 268, 281 Salivary glands, 236, 281 Saponins, 281, 285 Scleroderma, 219, 242, 282 Sclerosis, 186, 219, 282 Screening, 88, 195, 229, 282 Second Messenger Systems, 264, 282 Secretion, 228, 233, 250, 254, 261, 262, 279, 282 Sedative, 77, 220, 227, 230, 237, 252, 256, 258, 261, 275, 282 Sedatives, Barbiturate, 282 Seizures, 225, 235, 269, 282 Selective estrogen receptor modulator, 282, 287 Selenium, 13, 282 Self Care, 192, 282 Semen, 140, 238, 276, 282 Semicircular canal, 254, 282 Seminal vesicles, 149, 282 Seminiferous tubule, 253, 282, 284 Semisynthetic, 229, 267, 282 Sensor, 133, 282 Sepsis, 23, 282 Sequencing, 32, 273, 282 Serine, 27, 240, 282 Serologic, 252, 283 Serotonin, 173, 218, 224, 243, 271, 279, 283, 286, 291 Sex Characteristics, 213, 216, 283, 288
311
Sex Determination, 187, 283 Shock, 46, 73, 215, 240, 283, 291 Signal Transduction, 70, 283 Silymarin, 100, 261, 283 Single-agent, 141, 155, 283 Skeletal, 12, 29, 81, 216, 233, 263, 278, 280, 283, 284 Skeleton, 251, 256, 275, 283 Skull, 233, 283, 288 Sludge, 165, 284 Small intestine, 221, 238, 250, 255, 284, 293 Smooth muscle, 215, 220, 224, 231, 241, 250, 262, 268, 284, 286 Social Environment, 92, 278, 284 Sodium, 14, 53, 55, 127, 128, 134, 137, 150, 165, 176, 214, 236, 247, 261, 278, 284, 292 Sodium Channels, 278, 284, 292 Soft tissue, 223, 242, 243, 283, 284 Solvent, 132, 134, 135, 146, 148, 211, 221, 242, 247, 266, 271, 275, 284 Somatic, 213, 239, 261, 270, 284 Sorbitol, 66, 284 Soybean Oil, 273, 284 Spasm, 218, 250, 266, 284, 288 Spasmodic, 194, 284 Spasticity, 208, 284 Specialist, 92, 199, 236, 284 Specificity, 44, 57, 213, 224, 240, 284, 289 Spectrum, 13, 16, 32, 131, 139, 284 Spermatozoa, 282, 284 Sphenoid, 268, 285 Spinal cord, 223, 227, 228, 232, 238, 260, 264, 267, 270, 280, 285 Spinal tap, 258, 285 Spleen, 215, 259, 285 Spontaneous Abortion, 38, 274, 285 Sporadic, 264, 280, 285 Sprains and Strains, 111, 112, 258, 285 Stabilization, 161, 285 Stabilizer, 225, 285 Statistically significant, 23, 125, 285 Steady state, 27, 285 Steatosis, 243, 285 Stem Cell Factor, 42, 228, 285 Sterile, 268, 285 Steroid, 19, 37, 135, 170, 197, 221, 233, 246, 281, 285 Stillbirth, 274, 285 Stimulant, 176, 224, 250, 285, 287 Stimulus, 238, 239, 255, 257, 285, 289 Stomach Ulcer, 198, 285 Strand, 13, 101, 273, 286
312
Acetaminophen
Stress, 4, 7, 9, 13, 20, 36, 41, 72, 84, 124, 198, 226, 233, 263, 267, 281, 286, 292 Stroke, 45, 59, 121, 138, 171, 182, 225, 255, 286 Stupor, 190, 263, 286 Subacute, 253, 286 Subarachnoid, 248, 272, 286 Subclinical, 253, 282, 286 Subcutaneous, 238, 286 Subspecies, 157, 284, 286 Substance P, 241, 260, 281, 282, 286 Substrate, 17, 19, 30, 41, 234, 241, 286 Sudden death, 30, 286 Sulfates, 37, 286 Sulfotransferases, 17, 37, 286 Sulfur, 237, 261, 286 Sulfuric acid, 286 Sumatriptan, 55, 177, 286 Superoxide, 10, 31, 36, 108, 129, 286 Support group, 163, 192, 286 Supportive care, 166, 286 Suppositories, 85, 245, 286 Suppression, 43, 233, 287, 295 Surfactant, 140, 265, 287, 294 Survival Rate, 24, 287 Suspensions, 127, 147, 287 Symphysis, 276, 287 Symptomatic, 15, 18, 69, 82, 95, 167, 216, 268, 287 Synapses, 264, 287 Synaptic, 283, 287 Synergistic, 125, 129, 287 Synovial, 163, 196, 287 Synovial Fluid, 163, 196, 287 Synovial Membrane, 287 Systemic, 10, 126, 162, 163, 165, 176, 177, 192, 215, 222, 235, 241, 253, 282, 287, 290, 293, 294 Systemic disease, 162, 287 Systolic, 251, 287 T Tacrine, 165, 287 Tamoxifen, 165, 282, 287 Tarsus, 244, 287 Telangiectasia, 187, 287 Temporal, 10, 31, 81, 94, 248, 287 Terminator, 236, 288, 295 Testis, 241, 288 Testosterone, 27, 288 Tetany, 268, 288 Tetracycline, 159, 288 Tetrahydrocannabinol, 224, 288
Thalamic, 219, 288 Thalamic Diseases, 219, 288 Thalassemia, 138, 288 Theophylline, 8, 147, 236, 278, 288 Thermal, 153, 163, 237, 265, 273, 288 Thiourea, 25, 288 Thoracic, 220, 288, 294 Thorax, 211, 258, 288 Threonine, 27, 282, 288 Threshold, 12, 242, 251, 289 Thrombin, 243, 273, 276, 277, 289 Thrombocytes, 273, 289 Thrombocytopenia, 65, 289 Thrombomodulin, 276, 289 Thromboplastin, 277, 289 Thrombosis, 61, 81, 277, 286, 289 Thromboxanes, 218, 234, 238, 289 Thrombus, 233, 253, 255, 273, 289, 293 Thymus, 252, 259, 289 Thyroid, 165, 255, 261, 268, 289, 291 Thyroid Gland, 268, 289 Thyroid Hormones, 261, 289, 291 Thyroxine, 214, 271, 289 Tin, 273, 289 Tissue Distribution, 31, 289 Tolerance, 130, 197, 212, 223, 246, 289 Tolmetin, 125, 289 Tonic, 232, 260, 290 Topical, 192, 219, 242, 250, 290 Torticollis, 194, 290 Toxins, 21, 30, 37, 40, 164, 217, 224, 240, 246, 253, 290 Trace element, 229, 265, 289, 290 Tracer, 7, 25, 139, 290 Trachea, 223, 242, 271, 289, 290 Tramadol, 54, 71, 83, 85, 125, 153, 290 Transaminase, 191, 290 Transcriptase, 141, 235, 236, 265, 290 Transcription Factors, 24, 29, 290 Transduction, 283, 290 Transfection, 29, 222, 290 Transfer Factor, 252, 290 Transferases, 247, 290 Transfusion, 138, 290 Translation, 24, 241, 291 Translational, 41, 291 Translocation, 10, 26, 47, 229, 241, 291 Transmitter, 211, 237, 255, 259, 265, 287, 291 Transplantation, 53, 63, 81, 162, 166, 228, 239, 252, 257, 291 Transurethral, 166, 167, 276, 291
Index
Transurethral Resection of Prostate, 276, 291 Trauma, 166, 196, 235, 264, 268, 291 Tricyclic, 252, 291 Trigger zone, 218, 255, 291 Troglitazone, 95, 165, 291 Tryptophan, 230, 283, 291 Tuberculosis, 232, 256, 258, 281, 291 Tuberculostatic, 255, 291 Tuberous Sclerosis, 187, 291 Tumor marker, 163, 222, 291 Tumor Necrosis Factor, 16, 21, 118, 291 Tyrosine, 31, 237, 291 U Ulcer, 270, 285, 291 Ultrafiltration, 248, 291 Unconscious, 209, 216, 252, 291 Univalent, 251, 267, 292 Uraemia, 268, 292 Urea, 220, 256, 292 Uremia, 256, 280, 292 Urethra, 221, 269, 276, 291, 292 Uric, 157, 247, 251, 278, 292 Urinary, 19, 32, 51, 52, 101, 167, 222, 224, 228, 266, 276, 280, 292, 294 Urinary Retention, 167, 292 Urinate, 292 Urticaria, 215, 228, 292 Uterine Contraction, 149, 292 Uterus, 227, 233, 240, 260, 275, 292 V Vaccination, 195, 292 Vaccine, 195, 213, 277, 292 Vagina, 140, 260, 292 Vaginal, 58, 140, 265, 292 Valproic Acid, 32, 292 Valves, 159, 292 Vancomycin, 147, 292 Varices, 17, 293 Vascular, 61, 142, 162, 165, 215, 224, 240, 248, 253, 258, 265, 272, 289, 292, 293 Vascular Resistance, 215, 293 Vasculitis, 268, 293 Vasoconstriction, 142, 241, 293 Vasodilation, 142, 268, 293 Vasodilator, 223, 237, 250, 265, 268, 270, 293 VE, 10, 102, 293 Vector, 290, 293 Vein, 216, 255, 265, 274, 293
313
Venous, 68, 157, 222, 234, 249, 251, 277, 293, 294 Venous blood, 157, 222, 293 Venous Thrombosis, 293, 294 Ventricle, 232, 278, 287, 293 Ventricular, 215, 232, 293 Venules, 153, 223, 225, 293 Vertigo, 237, 293 Vesicular, 247, 261, 293 Vestibular, 26, 293 Vestibule, 229, 254, 282, 293 Veterinary Medicine, 94, 183, 293 Villi, 139, 293 Vinyl Chloride, 165, 293 Viral, 13, 23, 66, 162, 192, 211, 218, 236, 240, 249, 253, 290, 294, 295 Viral Hepatitis, 23, 162, 249, 294 Viral vector, 24, 294 Virulence, 220, 290, 294 Virus, 110, 140, 192, 211, 218, 227, 245, 290, 294 Virus Diseases, 218, 294 Viscosity, 145, 211, 280, 294 Vitro, 8, 10, 13, 14, 15, 24, 25, 27, 29, 32, 34, 40, 48, 56, 75, 81, 92, 100, 134, 140, 239, 253, 273, 281, 294 Vivo, 8, 10, 16, 25, 32, 33, 41, 140, 294 W Wakefulness, 235, 294 Warfarin, 62, 89, 294 Wetting Agents, 265, 294 Wheezing, 170, 294 White blood cell, 217, 253, 257, 259, 262, 272, 294 Windpipe, 271, 289, 294 Withdrawal, 227, 235, 260, 267, 294 X Xanthine, 129, 294 Xanthine Oxidase, 129, 294 Xenobiotics, 11, 19, 21, 28, 30, 38, 295 Xenograft, 216, 295 X-ray, 23, 27, 196, 243, 259, 265, 285, 295 Y Yawning, 130, 295 Yeasts, 244, 271, 295 Z Zidovudine, 33, 119, 120, 295 Zygote, 231, 295 Zymogen, 276, 295
314
Acetaminophen
Index
315
316
Acetaminophen
