AMANTADINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Amantadine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00051-2 1. Amantadine-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 amantadine. 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 AMANTADINE ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Amantadine................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 27 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. NUTRITION AND AMANTADINE ................................................................................. 73 Overview...................................................................................................................................... 73 Finding Nutrition Studies on Amantadine ................................................................................. 73 Federal Resources on Nutrition ................................................................................................... 75 Additional Web Resources ........................................................................................................... 76 CHAPTER 3. ALTERNATIVE MEDICINE AND AMANTADINE ........................................................... 77 Overview...................................................................................................................................... 77 National Center for Complementary and Alternative Medicine.................................................. 77 Additional Web Resources ........................................................................................................... 83 General References ....................................................................................................................... 84 CHAPTER 4. PATENTS ON AMANTADINE ....................................................................................... 85 Overview...................................................................................................................................... 85 Patents on Amantadine................................................................................................................ 85 Patent Applications on Amantadine............................................................................................ 89 Keeping Current .......................................................................................................................... 93 CHAPTER 5. BOOKS ON AMANTADINE ........................................................................................... 95 Overview...................................................................................................................................... 95 Chapters on Amantadine ............................................................................................................. 95 CHAPTER 6. PERIODICALS AND NEWS ON AMANTADINE ............................................................. 99 Overview...................................................................................................................................... 99 News Services and Press Releases................................................................................................ 99 Academic Periodicals covering Amantadine.............................................................................. 100 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 103 Overview.................................................................................................................................... 103 U.S. Pharmacopeia..................................................................................................................... 103 Commercial Databases ............................................................................................................... 104 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 107 Overview.................................................................................................................................... 107 NIH Guidelines.......................................................................................................................... 107 NIH Databases........................................................................................................................... 109 Other Commercial Databases..................................................................................................... 111 APPENDIX B. PATIENT RESOURCES ............................................................................................... 113 Overview.................................................................................................................................... 113 Patient Guideline Sources.......................................................................................................... 113 Finding Associations.................................................................................................................. 115 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 117 Overview.................................................................................................................................... 117 Preparation................................................................................................................................. 117 Finding a Local Medical Library................................................................................................ 117 Medical Libraries in the U.S. and Canada ................................................................................. 117 ONLINE GLOSSARIES................................................................................................................ 123 Online Dictionary Directories ................................................................................................... 123
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AMANTADINE DICTIONARY.................................................................................................. 125 INDEX .............................................................................................................................................. 185
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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 amantadine 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 amantadine, 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 amantadine, 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 amantadine. 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 amantadine, 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 amantadine. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON AMANTADINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on amantadine.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and amantadine, 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 “amantadine” (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: •
Hepatitis C Virus Infection and Renal Transplantation Source: American Journal of Kidney Diseases. 38(5): 919-934. November 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Website: www.harcourthealth.com. Summary: With the success of organ transplantation, liver disease has emerged as an important cause of morbidity (illness) and mortality (death) of renal (kidney) transplant recipients. Numerous studies performed during the 1990s have shown that hepatitis C virus (HCV) infection is the leading cause of chronic liver disease among renal transplant (RT) recipients. This article reviews the interrelationship of HCV infection and kidney transplantation. The transmission of HCV by transplantation of a kidney
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Amantadine
from an HCV infected organ donor has been shown unequivocally. Liver biopsy is essential in the evaluation of liver disease of RT recipients, and histological studies have shown that HCV related liver disease after renal transplantation is progressive. The outcome of HCV related liver disease is probably more aggressive in RT recipients than immunocompetent individuals (those with well functioning immune systems). Various factors can affect the progression of HCV in the RT population: coinfection with hepatitis B virus, time of HCV acquisition, type of immunosuppressive treatment, and concomitant alcohol abuse. The role of virological features of HCV remains unclear. The natural history of HCV infection after renal transplantation is under evaluation; however, recent surveys with long followups have documented adverse effects of HCV infection on patient and graft survival in RT recipients. Use of renal grafts from HCV infected donors in recipients with HCV infection does not appear to result in a greater burden of liver disease, at least for a short period. The association between HCV and new or recurrent glomerulonephritis after RT has been hypothesized and is an area of avid research. Reported studies do not support interferon (IFN) treatment for RT recipients with chronic hepatitis C because of the frequent occurrence of graft failure, and information on the use of other types of IFN or combined therapy (IFN plus ribavirin or amantadine) is not yet available in the RT population. 2 figures. 134 references.
Federally Funded Research on Amantadine The U.S. Government supports a variety of research studies relating to amantadine. 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 amantadine. 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 amantadine. The following is typical of the type of information found when searching the CRISP database for amantadine: •
Project Title: ACTG 301, TRIAL OF MEMANTINE FOR ADC AS TREATMENT W/ ANTIRETROVIRAL THERAPY Principal Investigator & Institution: Auerbach, Sanford; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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).
Studies
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Project Title: ACTG 301: MEMANTINE FOR AIDS DEMENTIA COMPLEX Principal Investigator & Institution: Lederman, Michael M.; Professor of Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: ACTG 301 is a randomized, double-blind, placebo-controlled trial of oral memantine taken alone or concurrently with an antiretroviral regimen in subjects with AIDS demential complex (ADC). The purpose of the study is to determine the safety and possible effectiveness of memantine, a drug that is used for the treatment of neurological disorders in Europe but is not FDA approved in the USA. The study will attempt to determine if memantine is helpful in curbing some of the effects seen with ADC. The trial runs 20 weeks (16 weeks of treatment and 4 weeks of washout) during which time each individual also receives 6 neuropsychological evaluations by the GCRC psychometrist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACTG 301--A RAND, DB, PC OF MEMANTINE FOR AIDS DEMENTIA COMPLEX Principal Investigator & Institution: Reichman, Richard C.; Professor; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 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: DEPENDENCE
AMANTADINE
AND
PROPRANOLOL
FOR
COCAINE
Principal Investigator & Institution: Kampman, Kyle M.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: The goal of this project is to evaluate the efficacy of amantadine and propranolol for the treatment of cocaine pendence in patients who present with severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), and have trouble initiating abstinence from cocaine. The initiation of abstinence in outpatient cocaine dependence treatment can be difficult. Treatment dropout rates are high and many patients continue to use cocaine. Preliminary data from our Center suggest that patients with high scores on the CSSA at treatment entry are much more prone to dropout and are less likely to achieve abstinence during the first several weeks of treatment. Amantadine is an indirect dopamine agonist that has been shown to be able to reduce dysphoria during early cocaine abstinence. In a recent double- blind trial, arnantadine was able to improve abstinence rates in a subgroup of patients with high CSSA scores at baseline. Among patient with initial CSSA scores above the 67th percentile, those treated with arnantadine submitted 50% benzoylecgonine-negative urines throughout the 4 week trial, whereas placebo treated patients submitted only 8% benzoylecgonine-negative urines. Propranolol is a beta adrenergic blocker that may be capable of reducing autonomic arousal associated with cocaine craving during early abstinence. In a recent trial, patients with high baseline CSSA scores treated with propranolol were significantly more likely to be retained in treatment than placebo treated patients (75% vs. 35%). Propranolol treated patients with high baseline CSSA scores also had significantly lower urinary benzoylecgonine levels
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Amantadine
during the 8 week trial than did placebo-treated, high CSSA patients. Amantadine, propranolol and the combination of the two medications will be evaluated in an 8 week, double-blind, placebo-controlled trial. For this trial, we will select cocaine dependent outpatients with high CSSA scores at intake who demonstrate a poor response to treatment by continuing to use cocaine during a two week baseline evaluation period. Continued use will be determined by two urine toxicology screens positive for benzoylecgonine during the 2 week baseline. Treatrnent will include weekly individual cognitive behavioral relapse prevention psychotherapy. Outcome measures will include quantitative urinary benzoylecgonine levels, self-reported cocaine use by timeline followback, and results from the Addiction Severity Index. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMANTADINE AS POTENTIAL TREATMENT FOR COCAINE ABUSE Principal Investigator & Institution: Fischman, Marian W.; Professor of Behavioral Biology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 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: AMANTADINE FOR AROUSAL IN PEDIATRIC TBI: A PILOT STUDY. Principal Investigator & Institution: Mc Mahon, Mary A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 30-JUN-2005 Summary: The long-term objectives of this proposal are to utilize pharmacological interventions to improve arousal and recovery in children following TBI. The specific aims are: 1) Conduct a trial of amantadine therapy in children who have impaired arousal following TBI, 2) Compare the interrater reliability and validity of three different measures of arousal in children with TBI, and 3) Describe the pharmacokinetics of amantadine in children with TBI. The experimental design is a randomized, doubleblind, crossover trial of amantadine and placebo. Subjects will include children, ages 518 years, admitted to an inpatient rehabilitation unit, who have impaired arousal related to TBI. Each subject will receive three weeks of amantadine and three weeks of placebo, with a one week washout period. Outcome measures will include two standardized measures, the Coma Recovery Scale (CRS) and the Coma/Near Coma Scale (CNCS), and two nonstandardized measures, a physician's clinical assessment of level of consciousness and the family's and physician's subjective evaluation of change in arousal. Each measure will be conducted at baseline and one to three times per week, depending on the measure. A portion of the CRS, the CNCS, and the physician's clinical assessment will be performed by two raters to determine the interrater reliability of each measure. The results of each measure will also be compared in an effort to establish validity. Serum amantadine levels will be obtained at designated times throughout the study and will be analyzed to provide estimates of individual pharmacokinetic parameters, including clearance, half-life, and volume of distribution, as well as noncompartmental parameters. The study results will provide an estimated treatment effect of amantadine in increasing arousal in pediatric TBI and data on the pharmacokinetics of amantadine in children. In addition, potentially useful standardized measures of
Studies
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arousal in children will be identified. This information will be integral in the design of a larger, multi-center study evaluating the efficacy of amantadine in children with TBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF THE EBOLA VIRUS VP24 CHANNEL PROTEIN Principal Investigator & Institution: Harty, Ronald N.; Assistant Professor; Pathobiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Ebola virus is an emerging, human pathogen causing deadly outbreaks of severe hemorrhagic fever. The molecular mechanisms of Ebola virus replication and pathogenesis are poorly understood, and consequently neither a vaccine, nor any specific antiviral therapy is currently available. Our preliminary data demonstrate that the VP24 protein of Ebola virus can function as a proton channel with pharmacological properties similar to those of the M2 protein of influenza A virus. The presence of an Ebola virus-encoded ion channel protein is rational since entry of Ebola virus is a pH-dependent process similar to that employed by influenza A virus. Importantly, the corresponding M2 proton channel of influenza A virus is the target of amantadine. Thus, it is likely that VP24 may serve as a similar target for the rapid development of anti-Ebola virus drugs. Our central hypothesis is that the VP12 protein of Ebola encodes a proton channel, and that this channel plays an important role in pathogenesis. Therefore, a better understanding of the structure and function of VP24 not only will provide insight into the molecular mechanisms of Ebola virus pathogenesis, but also may identify a novel therapeutic target for inhibiting Ebola virus replication. To define the biologically active structure and physiological/pathological functions of VP24 during Ebola virus infection we will, i) define domains within VP24 that regulate channel activation and proton permeation (Specific Aim 1), ii) identify domains within VP24 that are important for both biological structure and function (Specific Aim 2). iii) determine the pharmacological sensitivity of the VP24 channel protein, and assess the effect of pH regulatory drugs on Ebola virus infection (Specific Aim 3). iv) define the role of VP24/VP40 interactions in mediating assembly/budding of Ebola virus (Specific Aim 4). Overall this application will address key mechanisms of Ebola virus pathogenesis that may lead to the development of novel paradigms with direct impact on the development of therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICALLY NEUROTOXICITY
SAFE
NMDA
ANTAGONISTS
PREVENT
Principal Investigator & Institution: Lipton, Stuart A.; Professor and Director; Burnham Institute 10901 N Torrey Pines Rd La Jolla, Ca 920371005 Timing: Fiscal Year 2002 Summary: In Project, we will test two types of clinically-safe N-methyl-D-aspartate receptor (NMDAR) antagonists for their ability to prevent hypoxic-ischemic damage relevant to mental retardation. In these studies we will attempt to ameliorate NMDARmediated neurotoxicity first in vitro and subsequently in vivo in stroke models with therapy initiated greater than or equal to 2 hours after the insult. First, open-challenge NMDA blockers (adamantanes) will be tested; one of these drugs, memantine, is currently in clinical use in Europe for other disorders such as Parkinson's disease and spasticity. Second to be tested is nitroglycerin (NTG), which generates a redox-related form of nitric oxide that NO-related species is transferred to cysteine sulfhydryl groups
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Amantadine
of the NMDAR, a reaction termed S-nitrosylation. Additionally, a series of novel compounds, nitro-memantines, combining the features of NO+ transfer with openchannel block, are being developed. These combinatorial drugs will target NO+ to the NMDAR via memantine and thus avoid systemic side effects of NO such as hypotension. These combinatorial drugs will target NO+ to the NMDAR via memantine and thus avoid systemic side effects of NO such as hypotension. These studies with novel and potentially safe NMDA antagonists have important implications for the treatment of mental retardation and developmental disabilities due to overstimulation of glutamate receptors. To try to extend the potential window of treatment after a stroke, we will attempt to intervene therapeutically in apoptotic pathways activated with a delay after excessive NMDAR stimulation. The pathways studied here involve the action of caspases in the intracellular signaling cascade leading to neuronal apoptosis. Inhibition of caspase activity pharmacologically and with a caspase dominant-negative transgenic mouse will be use din conjunction with fluorescent indicators for Ca2+, reactive oxygen species, mitochondrial membrane depolarization, and lipid peroxidation in an attempt to decipher where caspases act in these signaling pathways that lead to hypoxic/ischemic neuronal damage. According, the Specific Aims of Project II are-2. To test drugs that we hypothesize nitrosylate the NMDAR to prevent hypoxicischemic neurotoxicity, including nitroglycerin (NTG) and novel nitro-memantine drugs that target NO+ to the NMDAR to avoid systemic side effects such as hypotension. 3. To characterize the action of caspases on intracellular signaling in excitotoxin-induced neuronal apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE RAPID EVALUATION STUDIES Principal Investigator & Institution: Shoptaw, Steven; Associate Research Psychologist; Friends Research Institute, Inc. Box 10676, 505 Baltimore Ave Baltimore, Md 21285 Timing: Fiscal Year 2002 Summary: There is no abstract specifically for this component of the application. This component proposes to study the efficacy of novel medications in the outpatient treatment of cocaine dependence. The methods proposed are described as rapid medication evaluations, and the purpose of the procedure is to determine if the studied medications are more effective than placebo, and if they are well-tolerated and safe. A three group design is employed, and the specific medications for the first proposed study are a combination of amantadine and baclofen, taurine, and placebo. Two clinical trials that will be conducted sequentially are proposed, and 120 subjects will be recruited for each study (35 per active medication group, and 50 for the placebo group, for each study). The final selection of medications will occur after input from NIDA?s MDD, as well as after reviewing current studies being conducted in the field, and consultation with colleagues in the area. These clinical trials will be conducted in the context of a standardized psychosocial treatment-Matrix Model Relapse Prevention. This is a manual-driven treatment that the investigative group established several years ago, and it provides a mechanism for ensuring all patients are exposed to similar nonpharmacologic treatment. In addition, this treatment provides a means for enhancing retention in treatment for patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE DEFICITS: TREATMENT OUTCOME IN COCAINE ABUSERS Principal Investigator & Institution: Aharonovich, Efrat; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): The goal of this developmental project is to study the relationship of cognitive deficits to treatment outcome in cocaine dependent patients. We propose to investigate the hypothesis that cognitive deficits compromise treatment compliance and outcome. Chronic cocaine abuse is associated with cognitive deficits including attention, memory, problem solving; abstract reasoning; and cognitive flexibility. Cognitive-Behavioral Therapy (CBT), a widely used intervention for cocaine addiction, makes cognitive demands in the same areas of cognitive functioning that are impaired in some cocaine-dependent patients. Thus, cognitive deficits may compromise the ability to participate in CBT, impeding treatment compliance and successful outcome. Our aims include: (1) investigating whether cognitive deficits predict time to dropout, session compliance, and drug use; (2) characterizing pre-treatment cognitive deficit profiles that identify patients at risk for dropout and relapse; and (3) completing development and implementation of patient and therapist ratings for apparent cognitive performance in CBT sessions and determining whether such ratings are related to dropout. The questions will be investigated by adding the proposed study onto an existing 14-week CBT/medication treatment study in cocaine dependent patients. Prior to treatment, 90 patients will receive a neuropsychological assessment battery in conjunction with the existing diagnostic battery. The newly developed therapist and patient assessment forms of apparent and perceived cognitive functioning and performance will be completed after each CBT session. Survival and other statistical methods will be used to analyze time to dropout, number of treatment sessions, and drug use as indicated by urine toxicology. The proposed study is innovative in its focus on the relationship between cognitive functioning and success of CBT-RP therapy overall, as specifically related to CBT-RP in cocaine abusers, and also in its focus on patient functioning on a session-by-session basis. A clearer understanding of the relationship of specific cognitive deficits to treatment outcome in cocaine abusers may serve as a first step towards the development of improved therapeutic strategies for this subgroup of cocaine abusers, a long-term objective of the research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOCHROME P450 SUBSTRATE SITING AND MOTION Principal Investigator & Institution: Mcdermott, Ann E.; Professor; Chemistry; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Rationalization and prediction of hydroxylation products of cytochrome P450 is crucial for understanding the mechanism of this enzyme and for understanding drug metabolism, but remains generally enigmatic. We propose studies of orientation of substrates in the enzyme pocket, and motion of substrates in the enzyme pocket, by new magnetic resonance methods. A longstanding hypothesis states that, counter to typical enzymological dogma, many substrates bound to the active site of (mammalian or prokaryotic) cytochrome P450 rotate rapidly on the timescale of enzymatic turnover; this putative motion might actually be reasonable and even needed for turnover, since the substrate pocket appears to be rather hydrophobic and chemically "featureless". If this motion does indeed occur, it would have important implications for understanding
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Amantadine
hydroxylation preferences. We have performed preliminary studies of substrate siting and motion for adamantane bound to the resting state of CP450cam, using deuterium magic angle spinning (MAS) SSNMR spectroscopy. These preliminary data support the hypothesis of extensive motion. On this preliminary basis we propose to conduct more detailed studies with medicinally relevant systems. In this preliminary study, competitive displacement and Curie-law temperature dependence of isotropic shifts were used to verify location at the active site. Simulation of deuterium spinning sideband intensities allowed us to determine the strengths of the electron-nuclear dipolar hyperfine coupling, the strength of the effective deuterium quadrupolar splitting (which serves as measure of local motion) and the Euler angles describing the mutual orientation of the dipolar and quadrupolar tensors. Simulations of analogous data from model compounds are reported in a recent publication; RMS agreements of approximately 5 percent are possible, and the simulations are used to determine distances to a precision of 0.5 Angstrom units up to a maximum "capture radius" of 7 Angstrom units, and angles were determined to within 20 degrees. Simulations of the data for enzyme-bound adamantane indicated an average metal-deuterium distance of 6.0 (+/- 0.2) Angstrom units and clear-cut evidence of a rapid high- symmetry motion. Computational and experimental improvements for analysis of the line-shape and spinning side-band intensities are proposed. We propose to characterize substrate motion for additional substrates (camphor, benzene, toluene, xylene, nicotine and warfarin), and an additional stable intermediate of the enzymatic cycle. Substrate geometry relative to the heme and substrate motion will be studies for the mammalian P450 enzyme using a membrane-mimic environment (DMPC/DHPC bicelles); information about substrate geometries is unavailable from crystallographic studies at present. Studies involving microbial detoxification enzymes with similar chemical mechanisms are also planned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINERGIC SUBSTRATES OF STARTLE GATING ACROSS SPECIES Principal Investigator & Institution: Swerdlow, Neal R.; Professor; Psychiatry; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-JAN-2004 Summary: For 20 years, systematic studies in rodents have identified specific neural substrates regulating pre-pulse inhibition (PPI) of startle, including parts of the prefrontal cortex, hippocampus, amygdala, ventral striatum and pallidum, and pontine tegmentum. These limbic cortico- striato-pallido-pontine (CSPP) substrates regulating PPI are relevant to several neuropsychiatric disorders, and are implicated in the reinforcing properties of drugs of abuse. Now that the neural substrates of PPI have been delineated in rats, the next major challenge is to develop the capacity to probe and understand this PPI-regulatory circuitry in humans. If neural circuit information, derived from animal studies, could be translated across species, PPI could become an important, new tool for understanding this circuitry in normal and neuropsychiatric disordered populations. Specific drug effects on PPI in rats are highly predictable, and are understood at the level of neural circuitry. The present proposal will initiate a translocational approach to understanding limbic CSPP circuitry, by assessing the homology of pharmacologic manipulations of PPI across species. In tests of PPI, startle habituation, latent inhibition and measures of sensory gating, we will carefully assess the time course and dose response effects of the direct dopamine (DA) agonists bromocriptine, per-golide and ropinirole, the indirect DA agonists amphetamine and
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amantadine, and an active comparison drug (caffeine) in normal humans. Contemporaneous measurement of physiological and psychological variables will facilitate interpretation of changes in the critical dependent measures. Based on initial results, we will assess DA agonist effects on the dependent measures after pretreatment with typical and atypical anti-psychotics. Future studies will assess the serotonergic, glutamatergic and nicotinic regulation of PPI and related measures, and sex differences and menstrual cyclicity of drug effects on these measures, in normal humans. Data from the proposed studies will provide new information for interpreting the neurochemical basis of PPI deficits in schizophrenic patients, as well as the sensitivity of these deficits to antipsychotics. By developing an important new strategy for under- standing limbic CSPP circuitry in humans, the proposed studies will have direct relevance to a broad range of issues in neuropsychiatry, including the neurobiology of drug abuse. More generally, these studies will begin the important process of examining the neurochemistry of sensorimotor gating processes that fundamentally shape behavior and cognition in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFICACY OF AMANTADINE HYDOCHLORIDE AFTER PEDIATRIC TBI Principal Investigator & Institution: Beers, Sue R.; Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 19-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant): The National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke have called for pilot clinical trials to investigate pharmacological interventions to improve outcomes in pediatric patients following traumatic brain injury (TBI). The present application is targeted to this agenda. TBI is the leading cause of long term disability in children, with related costs exceeding over $12 billion a year. While no level of injury severity is completely free of consequences, the deficits associated with more severe injury have significance educational and vocational ramifications that continue years after injury. The neurobehavioral sequelae of TBI (e.g., poor working memory, difficulty in allocation of attention, depression) suggest the presence of executive deficits that are consistent with trauma commonly affecting the frontal brain regions. The literature demonstrates that frontal cortex activity, enervated by mesocortical dopamine projections, is critically involved in the strategic actions that are frequent diminished after TBI. Treatment with amantadine hydrochloride (AMH), a dopamine agonist, has been shown to improve behavioral symptoms and executive function in adults after brain injury. While AMH is used clinically in children, there is a dearth of rigorous studies that evaluate the true efficacy of this drug. Therefore, the goal of this pilot clinical study is to evaluate the overall safety and efficacy of AMH in improving the behavioral management, functional outcome, and neuropsychological status of children who have experienced TBI, and to use this information to organize and design a Phase III clinical trial of AMH. The specific aims of this research include 1) To determine if treatment with AMH address frontal dysfunction begun > 6 months after TBI and maintained for 12 weeks is safe and effective when compared to standard clinical care; 2) To determine the sensitivity of specific neuropsychological instruments to assess outcome after treatment with AMH; and 3) To determine if variables related to either the injury or the subject impact treatment outcome. This randomized controlled study of AMH incorporates a repeated measures design. After screening procedures to document behavioral deficits suggesting executive dysfunction, we will stratify 120 children from 6
12
Amantadine
through 16 years into three age groups, randomizing subjects into a treatment or standard care group. All subjects will complete baseline and 12-week follow-up neuropsychological testing that provides a focused assessment of executive skills. In addition to demonstrating the safety and efficacy of AMH, we expect to identify complex interactions among injury- and treatment-related variables (age at injury, age at treatment, medication status, and injury severity). This information will optimize the design of Phase III clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXCITATORY AND INHIBITORY PATHWAYS FOR COCAINE TREATMENT Principal Investigator & Institution: Nunes, Edward V.; Associate Professor of Clinical Psychiat; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002 Summary: Project 1 will test two new medications for cocaine dependence in late Phase II trials memantine, a non-competitive NMDA antagonist used in Europe to treat dementia, and gabapentin, an anti-convulsant which acts by enhancing GABA activity in the CNS. The pivotal role of dopamine in the rewarding and addictive properties of cocaine remains clear, but the lack of success with anti-depressants and dopamine agonists in clinical trials suggests other approaches to manipulating the dopamine system in cocaine dependent patients should be sought. Excitatory amino acids (EAA) and the inhibitory neurotransmitter gamma amino butyric acid (GABA) exert reciprocal influences on dopamine neurons in the reward system, the former promoting and the latter inhibiting dopamine release. In addition, excitatory amino acids may promote the development of conditioned responses to cocaine cues which perpetuate addiction. This suggests the hypothesis that either EAA antagonists or GABA agonists may be effective for cocaine dependence by reducing cocaine-induced dopamine release and/or attenuating conditioning to cocaine cues. Two 12-week prospective, parallel-groups, randomized, placebo- controlled trials (Study 1: memantine versus placebo; Study B: gabapentin versus placebo) will be conducted in outpatients with cocaine dependence. The specific aims will be to determine whether memantine (Study A) or gabapentin (Study B) are superior to placebo in reducing cocaine use, cocaine craving, psychological symptoms, functional impairment, and attrition from treatment. In addition, these studies are part of a larger effort in this MDRU to develop optimal clinical trial designs for testing cocaine pharmacotherapies. Patients will be asked to attend the clinic three times weekly for medication and urine monitoring and participate in weekly placebo lead in during which patients will be required to attend at least four out of six visits in order to enter the randomized trial. These design features are intended to produce a compliant sample to maximize power to detect medication effects. Cocaine use during the lead in will be examined as a predictor of cocaine use outcome and of medication effects in order to evaluate the utility of the placebo lead in as a design feature for cocaine medication development trials, Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FATIGUE AND SLEEP ABNORMALITIES IN HIV INFECTION-IDENTIFICATION OF THERAPIES Principal Investigator & Institution: Mitler, Merrill M.; Scripps Research Institute Tpc7 La Jolla, Ca 92037
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Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FIV/CAT SYSTEM--A MODEL FOR LENTIVIRUS INDUCED DISEASES Principal Investigator & Institution: Phillips, Tom R.; Assistant Member; Vaccine Research Institute of San Diego San Diego, Ca 92109 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-AUG-2004 Summary: As part of the Scripps AIDS Dementia Center grant, we have established a feline colony for the purpose of developing the FIV/Cat system as an animal model to study the neurologic aspects of AIDS. Because of the success in developing this model, the number of investigators and experiments utilizing this system has precipitously grown since the Center's inception. Thus, the requirement for cats from both within and outside of the Center has exceeded the available funds to support the research. In this proposal, we request assistance to help further develop the FIV/Cat system as an animal model for the neurologic aspects of HIV-1 induced disease. This colony serves our Center's researchers as well as several collaborating investigators. Thus, our colony can be considered of emerging national importance. We have made great strides in developing the feline/FIV model as a legitimate system for the study of lentivirus induced neurologic disease, as several parameters have been established to monitor the effects of virus infection on the CNS. However, to fully develop the FIV/Cat system, further studies are required. Developing the FIV/Cat system as a predictive animal model to examine the effects of treatment interventions on the neurologic aspects of the disease would enhance the utility of this modeling system. To this end, we now want to expand our ongoing studies to investigate the effects of antivirals on neurologic aspects of the disease as well as the adaptive response of the virus to the drug. We propose the following specific aims: 1) Specifically develop the FIV/cat system as an animal model for examining effects of antivirals on the neurologic disease progression of lentivirus infections. 2) Monitor the animals for the development of drug-resistant mutants and map the genetic determinants associated with the resistant phenotype. 3) determine if FIV-drug resistant mutants maintain their neurovirulence. Our long term objective is to develop the FIV-cat system as a predictive animal model for assessing the effects of antiviral compounds on the neurologic aspects of lentivirus diseases. The completion of these specific aims will further validate the FIV/cat system as a predictive animal model as well as provide valuable insights into virus-host-drug interactions, thus, further establishing and refining the FIV/cat system as a research resource. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEQUENCES
FLUORESCENT
TISH
PROBES
FOR
CANCER
REVELANT
Principal Investigator & Institution: Fresco, Jacques R.; Professor; Molecular Biology; Princeton University 4 New South Building Princeton, Nj 085440036 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2005 Summary: (Applicant's Description) Fluorescent TISH Probes for Cancer-relevant Sequences Gene amplification, substitution and deletion mutations are associated with the molecular pathology of various malignancies, including breast, cervical and gastric cancers, as well as colon and lung cancers and tumors of the nervous system. Multidrug resistance of cancer cells is also associated with gene amplification. Amplification of
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Amantadine
erbB-2 (HER-2/neu) and N-myc genes is particularly correlated with poor prognosis in breast and cervical cancers and neuroblastoma, respectively. Methods that could simply and reliably detect such aberrations and quantitate them can therefore be of great value for diagnosis, for following the efficacy of treatment, and for reliable prognosis. Currently, detection of point-mutational events represents a major experimental effort. In the case of gene amplification as well, the methods are arduous, require relatively large samples, and they are of variable reliability. This project has a two-fold aim. One is to apply the methodology of TISH (third strand in situ hybridization of fluorescent probes via triplex formation, which avoids the need for DNA denaturation) for the cytogenetic quantitative analysis of these aberrations. TISH has three major advantages: greater sensitivity and quantitative reliability, and importantly, greater sequence specificity. The second parallel aim is to develop suitably intense and non-quenching fluorescent TISH probes. For this purpose, a major effort will be mounted to develop dendritic nuclei with fluors attached by rigid linkers that prohibit their interaction, therefore preventing the quenching of fluorescence. In this way, it is hoped to enhance the sensitivity of fluorescent probe detection by 1-2 orders of magnitude, thereby assuring that TISH probes can be reliably used for analyzing amplified genes and ultimately for detection of mutations in single-copy genes in situ. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GABAERGIC & GLUTAMATERGIC AGENTS--COCAINE USE IN METHADONE MAINTENANCE Principal Investigator & Institution: George, Tony P.; Associate Professor of Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2003 Summary: This section of this Medications Development Unit (MDU) outlines phase ll screening studies for armacotherapy of cocaine use in methadone- maintained subjects with agents that act through GABAergic or lutamatergic mechanisms. These studies would be carried out in two parts, with GABAergic agents being tested in Years l-2, and glutamatergic agents in Years 3-5. Our group has a long history of completing pharmacotherapy trials in cocaine-using methadone subjects, and examples have included desipramine, mazindol, amantadine, bromocriptine and bupropion. Preclinical evidence indicates that GABA and glutamate systems can modulate dopamine reward pathways which are thought to underlie the addictive properties of cocaine, and agents which modulate GABA and glutamate systems can reduce the reinforcing properties of cocaine in animal models. The GABAergic agents chosen for these pilot studies are: l) the GABAB agonist baclofen; and 2) the selective GABA reuptake inhibitor tiagabine. The glutamatergic agents chosen for phase I studies are: l) the NMDA receptor antagonist acamprosate and 2) the pre~synaptic glutamate release inhibitor lamotrigine. A total of 60 subjects will be recruited into each study for a total of 120 subjects over the entire five year period. Subjects will be randomized to one of five cells: placebo or two different doses of either baclofen or tiagabine (Study 1) or acamprosate or lamotrigine (Study 2) for a total of 8 or 12 weeks of active treatment for GABAergic and glutamatergic agents respectively. At the end of the active trials, medications would be tapered over a two week period. Primary outcomes will be selfreported cocaine use, three times weekly urine toxicology for the cocaine metabolite benzoylecgonine and treatment retention. It is hoped that we will demonstrate the efficacy and safety one or more of these agents for cocaine use in opiate-maintained subjects, and if encouraging results are obtained, phase ll controlled studies would be planned with promising candidates identified from these phase ll screening trials.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFLUENZA VIRUS ASSEMBLY AND VIRULENCE Principal Investigator & Institution: Pekosz, Andrew S.; Assistant Professor; Molecular Microbiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 30-NOV-2007 Summary: (provided by applicant): The assembly of influenza A virus involves the specific interaction of several viral components at a predetermined location within the virus-infected cell. The viral proteins involved in this process are key components in the generation of vaccines as well as in the adaption of virus to new hosts, but precise roles in the assembly process have yet to be ascribed or identified. The application of reverse genetics techniques and new technologies such as RNA interference allows for the precise dissection of the assembly process and the determination of precise functional domains important for virus assembly to take place. To fully understand the viral factors involved in influenza A virus assembly, a detailed molecular investigation of the domains of the M1 (matrix) and M2 proteins involved in virus assembly will be undertaken. The amino acid sequences in M1 and M2 that are important in targeting the proteins to sites of virus budding will be identified. The mechanism behind the anti-M2 antibody mediated inhibition of influenza A virus budding will be elucidated and specific interactions between the M1 protein and the M2 cytoplasmic tail will be characterized. Finally, the intracellular localization of M1 will be analyzed in cells infected with recombinant viruses bearing mutations in the HA and NA proteins that prevent their association with glycolipid rafts or the apical membrane. Recombinant viruses bearing specific mutations in one or several viral proteins will be generated and characterized for their sensitivity to anti-M2 antibodies, antiviral drug sensitivity and virulence. These studies should shed additional light on the mechanisms responsible for the generation of new, highly virulent influenza A viruses as well as further define the interactions that govern antibody and drug sensitivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INNOVATIVE PHARMACOTHERAPY
APPROACHES
FOR
COCAINE
Principal Investigator & Institution: Pettinati, Helen M.; Director; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: This application is for a Medication Development Unit (MDU) which will complement our existing program of research in finding effective treatments for drug addiction. The tight integration of this MDU within the general umbrella of the Penn/VA Center for Studies of Addiction, allows us to propose a substantial amount of research (two large scale clinical trials, a laboratory study, and pilot projects) with minimal new resources. Specifically, the theme of this center focuses on the use of innovative strategies to find effective pharrnacotherapies to treat cocaine dependence. The core facilities Include a data management unit, significant computer support including a wide area network to facilitate Center communication, human labs, and a urine testing lab. This Center proposal includes a core and three projects plus a series of pilot studies on GABAergic agents. The core will have general administrative functions and help with the overall scientific direction, data management, common clinical services, subject recruitment, pharmacy services, laboratory functions, and coordination of the individual projects. In addition, the core will conduct pilot studies of promising
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Amantadine
pharmacological agents for cocaine dependence related to enhancing GABAergic activity, creating new directions for clinical trials. Project l investigates the use of amantadine and propranolol, alone or in combination, in subjects in the early stages of their recovery who have recently had a positive urine for cocaine and a high score on the Cocaine Selective Severity Assessment. Our preliminary data suggest that pharmacotherapy is particularly helpful for this subgroup of patients. Project 2 will test the use of naltrexone and disulfiram, alone and in combination, in the treatment of cocaine dependence complicated by alcohol dependence. This study attempts to replicate and extend recent findings that disulfiram reduces both cocaine and alcohol use in cocaine- alcohol dependent patients. In addition, it extends our earlier pilot study of naltrexone on alcohol abusing cocaine dependent subjects. The combination of these two compounds may be particularly helpful in enhancing treatment retention and reducing cocaine and alcohol use. Project 3 evaluates the effects of various medications on cue reactivity and the predictive validity of cue reactivity on clinical outcome. By taking subjects randomized from Project 1, 2 and the core pilot projects, subjects will be administered cue screening prior to receiving study medications, and again about 4 weeks into the clinical trial while on study medications. In addition to testing specific medications, the Center will utilize an integrated series of projects to improve our understanding of cocaine treatment as it relates to stabilization and detoxification as treatment goals versus reducing the number and intensity of cocaine relapses. In addition we will investigate the use of cue reactivity as it predicts treatment outcome and as a possible screening tool for new medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAPPING THE M2 PROTON CHANNEL BY H/D-LC-MS Principal Investigator & Institution: Griffin, Patrick R.; Cso and Executive Vice President Researc; Exsar Corporation 11 Deer Park Dr, Ste 103 Monmouth Junction, Nj 08852 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 14-NOV-2003 Summary: (provided by applicant): We have developed high-throughput mass spectrometric methods for mapping the structure and the location of active sites of proteins. These methods rely on measuring changes in solvent-accessibility and stability in the presence and absence of a small or large molecule ligands, as determined from the exchange rates of solvent deuterons with amide NH and sidechain CH groups of the protein; collectively we term this hydrogen-deuterium-exchange LC-MS, or H/D-LCMS. Although our methods are being extensively developed to assess the binding of drugs to water-soluble proteins, they have not yet been applied to membrane proteins. Here we propose to extend our technology to study a relatively simple, but medicinally important membrane protein, the proton channel from influenza A virus (M2). This M2 proton channel is essential to the infectivity of the virus, and is the target of the antiinfluenza drugs, amantadine and rimantadine. We have three specific aims in this proposal: 1) Using M2 as a model, we will extend H/D-LCMS to characterize the structures and binding sites of membrane proteins. 2) The methods will then be used to map the solvent accessibility of amides and sidechains within the M2 proton channel. Specifically we will determine the extent to which we can map the structured watersoluble regions of the protein, the membrane-contacting regions, and the solvent-filled channel of the M2 protein. 3) We will determine the feasibility of using these methods to assess structural changes associated with ligand binding and alterations in pH; the M2 proton channel is activated at the low pH (near 5.5) where it functions. We therefore will examine whether our technology can be used to evaluate differences in its H/D exchange at pH 7 versus 5, in the presence and absence of amantadine. The results will
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have an impact on our knowledge of this important therapeutic target, and will have broad impact on the future analysis of membrane-protein structures. With methods in place, we will be able to define structure perturbations of M2 upon binding other amantidine-related ligands and new pharmacophores. One long-term goal will be to aid the discovery of new antiviral agents. In addition, the methods developed herein will fill the gaps in the ability to explore structures of membrane proteins. We hope to develop H/D exchange into platform for the study of important membrane-associated drug targets, such as G-protein coupled receptors (GPCRs). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDICATIONS DEVELOPMENT FOR ALCOHOL ABUSE: NMDA AGENTS Principal Investigator & Institution: Evans, Suzette M.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 24-SEP-1999; Project End 30-JUN-2004 Summary: Alcohol use disorders are an enormous public health problem. Recent advances in understanding the effects of alcohol on the brain and behavior present an opportunity to advance medication development. Neurotransmission at NMDA receptors may contribute to many of alcohol's effects and it is postulated that modulation of NMDA neurotransmission may be effective in the treatment of alcohol use disorders. In fact, the NMDA modulator acamprosate is effective in the treatment of alcohol dependence. We propose to develop and implement human laboratory and clinical models to screen promising medications and establish whether modulation of the NMDA receptor system with memantine, a non-competitive NMDA antagonist, has beneficial effects in the treatment of alcohol dependence. For comparison we will test acamprosate, a polyamine site NMDA modulator with proven efficacy in the treatment of alcohol dependence. Residential laboratory studies will include paradigms designed to model multiple aspects of alcoholism using non-treatment seeking moderate to heavy social drinkers. In Studies 1 and 2 we will compare the interaction of acute pretreatment with acamprosate or memantine on the effects of alcohol intoxication. In Studies 3 and 4 we will evaluate the effects of maintenance on acamprosate or memantine on reactivity to alcohol cues, and we will also evaluate the effects of maintenance on acamprosate or memantine on alcohol choice and self-administration. In Study 5 we will evaluate the effects of acamprosate and memantine, given acutely and repeatedly, on the discriminative stimulus effects of alcohol. In Study 6, we are proposing a strategy for improving initial pilot screening of medications that involves testing acamprosate, memantine and placebo in a relatively small N. placebo-controlled trial in alcoholdependent individuals. Inclusion of this clinical trial model is important for predicting the validity of the laboratory models we are proposing. The experimental verification that acamprosate and memantine modulate alcohol intoxication, self-administration, cue-reactivity, discriminative effects, and preliminary clinical efficacy, could have major implications for the treatment of alcohol use disorders. This application represents, to our knowledge, the first attempt to systematically evaluate the contribution of NMDA receptor-mediated neurotransmission on alcohol's action in humans from the perspective of medication development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Amantadine
Project Title: MOLECULAR ANALYSIS OF NMDA RECEPTOR MODULATORY SITES Principal Investigator & Institution: Chen, Vincent; Burnham Institute 10901 N Torrey Pines Rd La Jolla, Ca 920371005 Timing: Fiscal Year 2002 Summary: The dual role of NMDA receptors in the normal and abnormal functioning of the nervous system imposes important constraints on possible therapeutic strategies aimed at ameliorating ro abating developmental disorders and neurological disease. Based on our groups previous work, two groups of drugs are likely to show promise for safe but effective pharmacological intervention to curtail excessive activity of the NMDA receptor: (i) memantine, a use-dependent and uncompetitive antagonist that is an NMDA open-channel blocker, and (ii) nitric oxide (NO)-related species (provided by nitroglycerin) that interact with redox modulatory sites on the NMDA receptor. In our preliminary results, we have demonstrated the following: 1) the glutamine/arginine/asparagine (Q/R/N) sites in the second membrane spanning (M2) domains of NMDAR1 and NMDAR2 subunits strongly affect memantine binding; 2) there exist three kinetically-distinct components of redox modulation on NR1a/NR2A heteromeric channels that are affected by redox agents; 3) each kinetic NR2A component or redox modulation can be attributed to interaction with a pair of cysteine residues on the NR1 or NR2A subunits and these subunits also affect modulation by Zn; 4) one cysteine residue on NR2A is predominantly responsible for modulation of the NMDAR activity by NO-related species. Furthermore, we recently isolated a novel NMDAR subunit, NR3A (previously designated NMDAR-L or khi-1), from the rat CNS. Coexpression of NR1/nr2a OR b/nr3a IN Xenopus oocytes decreases unitary conductance in single-channel recordings. Conversely, NR3A-deficient mice have larger than normal NMDA-evoked currents. The new project will further study these knock-out mice. We also obtained a near full-length cDNA clone of a second novel NMDAR subunit, tentatively named NR3B since it shows high sequence identify to NR3A. We propose: [1] To study the structural determinants of memantine binding in the channel pore of the NMDAR, [2] To characterize the cysteine residues underlying redox, Zn, and No modulation of the NMDAR, [3] To elucidate the molecular mechanism of action of NR3A whereby it decreases NMDAR-activated current. [4] To clone and characterize a second novel NMDAR subunit, NR3B, in order to determine the function role that it subserves in the developing brain. Most importantly, drugs developed in Project will be used for neuroprotection from hypoxic-ischemic injury and AIDS-related neuronal damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR PHARMACOLOGY OF GLUTAMATE RECEPTORS Principal Investigator & Institution: Williams, Keith P.; Physiology and Pharmacology; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 29-FEB-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTICENTER TBI CLINICAL TRIALS NETWORK Principal Investigator & Institution: Meythaler, Jay M.; Professor; Physical Medicine & Rehabilitation; University of Alabama at Birmingham Uab Station Birmingham, Al 35294
Studies
19
Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Traumatic brain injury (TBI) is one of the most significant causes of disability to able bodied persons in the most productive period of their lives. The most common cause is high-speed transportation accidents, and these result in a mechanism of injury commonly described as diffuse axonal injury (DAI). DAI causes a reduction in the turnover of dopamine in the brain. Basic science research has suggested that increasing dopamine turnover at the synaptic level may have a beneficial effect on recovery from brain injury. One medication, Amantadine, has been the subject of considerable interest and clinical use. It stimulates the release of dopamine from the presynaptic neuron, inhibits the re-uptake of dopamine, may directly interact with postsynaptic dopamine receptors and is a weak N-methyl-D-aspartate (NMDA) antagonist. The concept study proposed herein will evaluate the early clinical use of Amantadine in TBI. This concept study is supported by the outcomes of a pilot study performed at UAB. However, the definite beneficial effect of Amantadine on brain injury recovery has never been demonstrated. Considering the widespread clinical application of Amantadine in TBI patients, a well-controlled prospective multicenter clinical trial should be carried out. This concept study, or any other(s) selected, will contribute to the multicenter TBI Clinical Trials Network. As Amantadine is generically available, there is little interest in it by the private sector. The study design is a single case double blind, randomized controlled trial. Utilizing well established outcome measures, including behavioral and cognitive, the investigators will attempt to establish the efficacy and side effects of Amantadine in the acute stages of recovery from TBI. This research has the significant possibility of reducing the disability and economic burden of these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPSYCHIATRY OF TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Kraus, Marilyn F.; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): This revised application for an academic career development award for clinical research (K23) outlines a program for training and research focusing on the evaluation and treatment of neuropsychiatric disorders secondary to traumatic brain injury (TBI). The particular focus of the research is on prefrontal dysfunction, as the frontal lobes are the most common site of lesion in TBI. This can result in impaired executive cognitive function, mood disorders such as depression, and behavioral changes such as apathy, impulsivity and aggression. Over 2,000,000 cases of TBI occur per year in the US, resulting in significant long term disability. These patients often present to psychiatry, but there are no clear guidelines on treatment of these neurobehavioral disorders. Frontal dysfunction has been shown to play a role in other psychiatric illnesses as well, such that research into effective treatments to improve frontal function could be broadly beneficial. There is a significant need to train psychiatric clinical researchers in this area. Current technologies in MRI, including functional MRI and techniques to assess white matter such as DTI (diffusion tensor imaging) have the potential to further understanding of this brain disorder. There are two primary aims of the proposed career development plan. First, the PI will learn to utilize state of the art structural and functional imaging methods of MRI, along with neurophysiological (oculomotor studies) and neuropsychological procedures, for assessing effects of frontal lobe injury. This will allow for a thorough delineation of the anatomic and neurobehavioral sequelae of TBI. Second, the PI will develop expertise in pharmacologic clinical trials in this special population. The lack of effective treatments
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Amantadine
to improve quality of life underscores the need to train psychiatric researchers with the necessary skills to fill this void. Further, the need for neuropsychiatric investigators trained to evaluate the cognition-enhancing properties of new pharmacotherapies will be very great in coming years. During the proposed career development program, the PI will utilize MRI and neurobehavioral assessments in a controlled clinical trial with amantadine in patients with frontal lobe dysfunction following TBI. The PI will learn to integrate imaging findings into clinical trials, developing guidelines for selection of therapeutic interventions. This application is designed to enable the candidate to transition into an independent clinical investigator with the necessary research skills needed to study neuropathology, outcomes, and interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL ISCHEMIA/STROKE
NMDA
RECEPTOR-BINDING
DRUGS
FOR
Principal Investigator & Institution: Wang, Yuqiang; Panorama Research, Inc. 2462 Wyandotte St Mountain View, Ca 94043 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 28-FEB-2003 Summary: (provided by applicant): The overall goal of this project is to develop a novel therapy for neurological injury. The concept is to combine two mechanisms known to provide neuroprotection from ischemic damage. Thus, we will combine a nitrone, known to have potent free radical scavenging activity with memantine, an open channel, uncompetitive NMDA receptor inhibitor, with demonstrated neuroprotective benefit in human clinical trials. In this proposal, we will synthesize novel dual functional memantine nitrones, demonstrate their neuroprotective effects both in vitro and in a rodent cerebral ischemia mice model. Based on these studies we are confident that this work will produce neuroprotective agents useful in neurodegenerative conditions such as stroke, epilepsy, trauma, and Alzheimer's disease, in addition to AIDS dementia. PROPOSED COMMERCIAL APPLICATION: A novel drug therapy for ischemia/stroke has a substantial commercial market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL-NON-VIRAL DELIVERY OF IFN GENE TO CANCER CELLS Principal Investigator & Institution: Bellocq, Nathalie; Insert Therapeutics, Inc. 2585 Nina St Pasadena, Ca 91107 Timing: Fiscal Year 2003; Project Start 11-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Interferon-alpha (IFNa) has been shown to be effective in treating cancer. One of the limitations of IFNa therapy as well as all protein therapeutics is their short half-life in vivo that require them to be administered frequently and create difficulties in maintaining steady state plasma levels. Gene therapy approaches could be employed to provide a more sustained release of IFNa in treating cancer. Insert Therapeutics (Insert) is developing new non-viral systemic nucleic acid delivery systems that can be used to provide a constant in vivo source of IFNa. The Insert non-viral delivery system involves several components: cyclodextrin-containing polycations (CDP), and a modifying agent that has a terminal adamantane (AD) for forming inclusion complexes with cyclodextrins on the surface of the colloidal CDP/nucleic acid particles. The polycation interacts with nucleic acids of sizes from short single-stranded oligonucleotides to large plasmids and self-assembles with the nucleic acids via electrostatic interactions to form colloidal particles. The polycations can mediate the transfection of cultured cells with high efficiency and completely protects
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the nucleic acid from nuclease digestion. The adamantane component self-assembles with the particles to modify the surface properties, thereby adapting the particles to be more suitable for systemic delivery. An important application of this modification technology is the addition of a ligand to target nucleic acids to specific tissues or cell types. When fully developed, the nucleic acid delivery system will overcome many of the problems associated with current gene therapy technologies. It will be a generalized delivery system that is non-immunogenic, non-toxic, stable in vivo, and amenable to large-scale production. In this phase I SBIR grant, we propose to develop a systemic IFNa DNA delivery vehicle to provide a sustained plasma release of IFNa for treatment of metastatic cancer. We will develop a therapeutic formulation of the delivery system for in vivo testing, optimize the conditions for the systemic delivery of the IFNa gene and test for efficacy in tumor bearing animal models. In future studies (phase II SBIR), we will conduct pre-clinical development of the delivery system so that it can be tested in clinical trials as a more efficient means to administer IFNa to patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARKINSON'S DISEASE RESEARCH TRIAL: CLINICAL CENTER Principal Investigator & Institution: Shannon, Kathleen M.; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Idiopathic Parkinson's Disease (IPD) is the second most common neurodegenerative disease, affecting an estimated 500,000 Americans; there are 35,000 new cases of IPD annually in the United States. The disease follows a progressive course, culminating in death or severe disability after about 20 years. Although there are medications that help to alleviate the symptoms of IPD by increasing central levels of the neurotransmitter dopamine, there remains no treatment to slow the relentless progression of the underlying degenerative process. A number of potential mechanisms of cell death have been illuminated by studies of pathology, epidemiology and experimental toxin-induced parkinsonism in animals. These include oxidative stress, protein aggregation, mitochondrial dysfunction, indirect excitotoxicity and apoptosis. A number of putative neuroprotective agents including propargylamines, complex I cofactors, substances affecting the mitochondrial energy potential, amantadine and others are emerging from the laboratory or early clinical trials. The Movement Disorders Group, of the Department of Neurological Sciences, Rush Medical College proposes to serve as one of 42 clinical centers for the Parkinson's Disease Neuroprotection Clinical Trial. The Rush Clinical Center will (1) participate in the design and implementation of pilot studies and the large simple clinical trials of 2 or more potential neuroprotective agents (2) recruit up to 12 subjects with early untreated Parkinson's Disease for pilot studies and 2 subjects per month for 36 months in the large simple trial and (3) collaborate with the Coordination and Statistical Centers in timely and accurate data collection and transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REACTIVITY
POLYNUCLEAR
CLUSTERS
IN
BIOLOGY
-
STRUCTURE,
Principal Investigator & Institution: Coucouvanis, Dimitri; Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 31-MAR-2006
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Amantadine
Summary: The oxidation and reduction of various substrates in living organisms are of fundamental importance to life sustaining processes. Multi-electron transfer processes, although less frequent in nature are of equally great importance. Included among the latter are: the 6e-reduction of N2 to ammonia in nitrogenase, the 6e-reduction of sulfite to sulfide and of nitrite to ammonia in sulfite and nitrite reductases respective And the 4e- oxidation of 2H20 to O2 in photosynthesis. This proposal is concerned with the synthesis and study of synthetic analogs for a) metalloenzymes involved in multielectron reduction and b) the non-porphyrin, non-Fe/S, iron centers active in oxidation processes. Specifically,: the synthesis, structures, spectroscopic properties and reactivitys of Fe/M/S (M=Mo,V) proposal. The Fe/M/S clusters are expected to sere as synthetic analogs for the Fe/M/S centers in the nitrogenases and alternate nitrogenases that contain vanadium or iron in place of molybdenum. The new types of Fe/S clusters that will be synthesized are designed as models for the P- clusters of nitrogenase. Superamolecular assemblies with attended Fe/S clusters containing pi acceptor ligands will be synthesized., and their possible function in the bimetallic activation and catalytic reduction of dinitrogen will be investigated. Multi-nuclear, mixed-ligand, carboxylatecatecholate complexes of first row elements will be studied as structure and reactivity models for the active sites in enzymes that catalyze the multi-electron oxidation of various substrates. The function of the catecholate ligands in these compounds, as storage sites of oxidizing equivalents, will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESPIRATORY VIRUS ION CHANNELS Principal Investigator & Institution: Pinto, Lawrence H.; Neurobiology and Physiology; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2003; Project Start 01-APR-1993; Project End 31-MAR-2008 Summary: (provided by applicant): Influenza contributes substantially to worldwide morbidity and mortality, and it has been estimated that the next influenza pandemic will result in over 80,000 deaths, 300,000 hospitalizations and 18 million outpatient visits in the United States. The M2 ion channel protein of influenza A virus is the target of the antiviral drug rimantadine, but its usefulness is limited by the formation of rimantadineresistant escape mutations within a few days of treatment. In order to develop more effective antiviral drugs, more information is needed about the M2 protein, especially the structure of its transmembrane pore and cytoplasmic domains and the mechanism by which it is activated. The following individual aims are designed to elucidate important features of the structure and function of the M2 protein. 1. Tryptophan 41 in the transmembrane pore is essential for activation of the M2 ion channel protein; we will perform functional and structural experiments to ascertain the role of tryptophan 41 in activation of the M2 protein. 2. The function of the M2 protein depends on the integrity of its cytoplasmic tail. Fluorescence and electroparamagnetic resonance (EPR) spectroscopy experiments will be performed to determine whether the cytoplasmic tail of the M2 protein forms a rosette lying on the membrane surface or forms a helix extending into the cytoplasm. 3. Key features of the structure of the pore and the cytoplasmic tail of the M2 ion channel will be determined using (EPR) spectroscopy. 4. In order to understand better the mechanism for resistance and to identify which functional properties of the channel are essential for its role in the virus life cycle, the functional properties of amantadine-resistant mutant M2 proteins will be characterized. 5. In a separate set of experiments we will use a sensitive method to test the NB protein of influenza B virus for ion channel activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPATIAL NEGLECT AND BIAS IN NEAR AND FAR SPACE Principal Investigator & Institution: Barrett, Anna M.; Medicine; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2009 Summary: (provided by applicant): This proposal examines spatial bias and distraction in near and far extrapersonal space. The Candidate previously observed far asymmetric attention in a patient with driving problems post-stroke. Far bias has both pragmatic and theoretical implications: it might induce impaired drivers to veer, causing accidents. Asymmetric visual-motor behavior in brain-injured subjects may be due to biased perceptual-attentional (PA) systems, biased motor-intentional (MI) systems, combined bias, or other factors. In five experiments, the Candidate will assess the proportion of error accounted for by PA and MI bias as subjects perform a video procedure in near and far space. In Experiments 1 & 2, she will manipulate performance-monitoring conditions to estimate PA/MI components of attentional bias and distractibility in near versus far space in post-stroke spatial neglect. Since months post-stroke, patients who have recovered on conventional visual-spatial tasks may still be still functionally disabled, in Experiment 3 the Candidate will examine whether separating PA and MI bias allows detection of persistent pathological errors. The Candidate will assess patients acutely post-stroke, and then repeatedly over a subsequent six months, examining evolution of near/far PA and MI bias. In Experiment 4, the Candidate will examine how monocular patching, amantadine, and combined treatment influence near/far spatial bias and distractibility. In Experiment 5, post-stroke subjects with presumed non-pathologic bias (compensated hemianopia) are compared with subjects with pathologic bias (contralateral/ipsilateral neglect) on the previous experiments. Considerable clinical and scientific training prepared the Candidate to begin this independent phase of her career. The Independent Clinical Investigator Award (K02) will provide essential time and resources as she continues her academic development. The present studies may clarify the neuropsychological mechanisms of orienting and visual-motor bias in near and far space after brain injury, contributing to the literature on brain attentional systems. However, this work may also advance understanding of safe and adaptive movement in complex environments by neurologically-impaired persons, improving their driving and functional independence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE OF M2 PROTON CHANNEL FROM INFLUENZA A VIRUS Principal Investigator & Institution: Degrado, William F.; Professor; Biochemistry and Biophysics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2005 Summary: Membrane proteins are of critical importance to nearly every aspect of cell physiology, comprising one quarter to one third of all proteins encoded by eubacterial, archaean, and eukaryotic organisms. Nevertheless, our understanding of their folding and structures is at a very primitive state when compared to that of water-soluble proteins. The M2 proton channel from influenza A virus provides an attractive system for understanding the folding and function of membrane proteins. This proton channel is essential to the survival of the virus, and is the target of the anti-influenza drugs, amantadine and rimantadine. The M2 proton channel is formed by the intermolecular association of four identical transmembrane helices, and a peptide (tmM2) spanning only the transmembrane helix of M2 forms amantadine- dependent channels in bilayers.
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Amantadine
In the past period, we have studied the thermodynamics of assembly of tmM2 and the full- length protein. Diffraction-quality crystals of tmM2 have also been obtained at low pH, where the channel is maximally active, as well as at pH 8.0, near the pH optimum for inhibition by the drug amantadine. Our specific aims for the current period are to: 1. Determine the structure of functional fragments of M2 using NMR, IR, and X-ray crystallography. 2. Determine what features in the sequence of M2 contribute to its thermodynamic stability. 3. Determine the mechanism of proton conductance by M2, and its inhibition by amantadine. 4. Design and structurally characterize a water-soluble version of M2, which retains the tertiary structure of M2 as well as its ability to bind amantadine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUDY OF RO64-0796 FOR TREATMENT AGAINST HUMAN INFLUENZA VIRUS Principal Investigator & Institution: Paar, David P.; Assistant Professor of Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002 Summary: GS4104 is a neuraminidase inhibitor with a demonstrated anti-human influenza activity in vitro and In vivo. It has been administered to humans without producing serious side effects. This study is a multicenter, double-blind, randomized, placebo controlled study with two study groups. Healthy adults, 14 years of age or greater will be randomly assigned to one of the two treatment groups: 1) Ro 64-796 75 mg po bid; 2) matching placebo. Duration of treatment is 5 days but the entire study duration is 21 days. The study will begin when the first cases of influenza are noted in the Galveston area. The specific aims are: 1) To investigate the clinical efficacy of Ro 640796 based on the time to treatment from onset of influenza symptoms, 2) To investigate the safety and tolerability of Ro 64-0796 in patients with influenza. The research hypothesis is that Ro 64-0796 recipients will have a shorter and less severe course of influenza than the placebo recipients. The results obtained from this study may provide an alternative to influenza vaccination, amantadine and rimantadine in this population. An alternative to these drugs would be medically useful since some people cannot tolerate influenza vaccines due to allergy or other adverse effects, influenza vaccine provides incomplete prophylaxis since the vaccine provides protection against influenza species from the previous year's strains of influenza, and the use of amantadine and rimantadine is limited by GI and CNS side effects as well as the development of viral resistance to these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCRIPTOMIC ANALYSIS OF THERAPEUTICS IN BRAIN TRAUMA Principal Investigator & Institution: Dixon, C Edward.; Associate Professor; Neurological Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Recovery of cognitive function after traumatic brain injury (TBD is a dynamic process that likely revolves multiple neural systems. Several studies by our laboratory and others indicate that cognitive recovery can be enhanced by post injury activation of dopaminergic systems or exposure to an enriched
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environment. The effectors of such therapeutic activation are likely to involve simultaneous gene expression changes m numerous neural systems. The recent development of DNA microarrays has allowed scientists for the first time the ability to observe thousands of gene expression changes in parallel. While there are limitations, DNA microarrays provide a new systemic view to study brain injury and the treatments that stimulate and enhance recovery of function. Recently, we have evaluated a number of DA agonists that are clinically used off label, for their ability to enhance recovery of cognitive function in our experimental model of TBI, and found three to be beneficial: amantadine hydroehloride, bromoeriptine, and methylphenidate. While all are putative dopaminergic agonists, they have varying degrees of specificity to DA systems. We have also observed that bromoeriptine treatment, when initiated 24 hours after TBI, can attenuate hippocampal cell death. This suggests that DA agonists may have mechanisms of action beyond just being DA replacement therapies (e.g. cell survival effects). In support of this concept, we have new pilot microarray data indicating that, relative to a vehicle treatment, the DA agonist methylphenidate treatment can enhance the gene expression of DA receptors, alter injury-induced inflammatory responses, and apoptosis related gene expression. DNA microarrays are well suited to investigate the effects of DA agonists on multiple pathways. The overall goal of the project is to determine common genes that are changed by these therapies and whether these gene expression changes can be further enhanced by the addition of enriched environment therapy. Tiffs exploratory R21 application (in response to RFA#HD-02-023) will obtain the preliminary information needed for a larger-scale R01 study to increase the number of cases, refine and increase the number of genes analyzed, and to more comprehensively study those genes whose expression are related to recovery of function after TBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF CHRONIC HEPATITIS C WITH AMANTADINE HYDROCHLORIDE Principal Investigator & Institution: Smith, Jill; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002 Summary: Treatment of chronic hepatitis C with interferon has been disappointing, with less than one-third achieving a sustained response and most experiencing significant side effects. A prospective open-labeled study was conducted to test the safety and efficacy of the anti-viral drug amantadine-HCL, in patients with chronic hepatitis C infection who had previously failed therapy with interferon. Patients were treated with amantadine-HCL 100mg given orally twice daily for six months. Thirty percent achieved a complete response (normalization of alanine aminotransferase, ALT, and loss of hepatitis C RNA), 40% a partial response (> 50% reduction in ALT and RNA), and 30% did not respond to amantadine-HCL. Response to therapy was significantly greater with amantadine-HCL compared to two time intervals of no treatment or therapy with interferon. The purpose of this study is to expand these findings to a larger trial designed as a randomized double-blind placebo controlled cross-over study. Eligible patients with hepatitis C will be randomized to receive either amantadine -HCL or placebo by mouth twice daily for six months. After six months, patients on placebo will be crossed over to amantadine treatment for the next six months and those on amantadine will be continued for an additional six months. Response to therapy will be assessed by a reduction in the hepatitis C viral RNA level and hepatic alanine aminotransferase levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Amantadine
Project Title: VIRAL MEMBRANE AND GLYCOPROTEIN STRUCTURE Principal Investigator & Institution: Harrison, Stephen C.; Professor; Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2002; Project Start 01-JAN-1977; Project End 31-MAY-2005 Summary: (Verbatim from the applicant's abstract) Emerging Infections: To study the mechanism by which influenza virus strains can emerge as infectious to humans, we plan to examine the X-ray structure and function of hemagglutinins from viral strains apparently limited to infecting animal reservoirs and for comparison human infectious strains from the major pandemics. Preferences for different sialoside linkages on cellular receptors correlate with the spread of infection in animals versus humans. One goal is to help explain observations like why outbreaks in the past two years in Hong Kong of avian virus infections in humans did not spread into the human population. Viral Entry Mechanisms: To investigate membrane fusion by influenza virus, we plan crystal structure studies of protein/detergent complexes of intact HA and HA2 and mechanistic studies of the interaction of HA with membranes and of intermediates in the fusion reaction. The hypothesis that HA2 in the low pH conformation observed by crystallography is membrane fusion active will also be tested with intact recombinant HA2 molecules transfected in cells suitable for membrane fusion assays. The hypothesis that the N- and C-terminal segments of HA1 plus all of HA2 (BHA's stem) was an ancestral membrane fusion protein will be tested by engineering such a protein, testing whether it can be proteolytically primed and activated by low pH, and whether the HA1 segments have a role, such as in the assembly of a putative multi-trimer containing pore. M2 Ion Channel: To generate structural information about the ion channel protein M2 of influenza virus we propose crystallization in detergent of bacterially expressed and refolded M2 tetramers that we have produced; and/or a tetramer of a channel-active synthetic transmembrane helix. Complexes with the inhibitory drug, amantadine, will also be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPITHELIUM
VOLTAGE-GATED
PROTON
CHANNELS
IN
ALVEOLAR
Principal Investigator & Institution: Decoursey, Thomas E.; Associate Professor; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 30-JUN-2004 Summary: First described in snail neurons in 1982, voltage-activated proton-selective currents have been found in patch-clamp studies of several mammalian cells, including rat alveolar epithelium (DeCoursey, 1991) and human neutrophils (DeCoursey and Cherny, 1993). These H+ channels are opened by a combination of membrane depolarization, cytoplasmic acidification, and extracellular alkalinization. They appear to have been designed to extrude acid from cells. In phagocytes they are activated during the respiratory burst, the process of killing bacteria, thus they facilitate the inflammatory response. In general, proton channels serve to maintain homeostasis in cells during periods of high metabolic activity. Less is known about these channels than about most ion channels. The H+ channel molecule has not been positively identified, partly because there are no potent and specific inhibitors. One aim of this project is to characterize the inhibition of H+ channels by organic drugs, such as local anesthetics. The mechanism of interaction between organic compounds (e.g., local anesthetics or amantidine) and the channel molecule will reveal clues to the nature of the conduction pathway by which protons cross the membrane. One of the most potent and best-known
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inhibitors of H+ channels is Zn2+. We will explore the mechanism of the strong pH dependence of Zn2+ effects, and test the hypothesis that Zn2+ binds to distinct sites at the external and internal side of the channel, perhaps the same regulatory sites that control the exquisite pH sensitivity of the voltage dependence of gating (Cherny et al, 1995). We will use reagents that modify specific amino acids (histidine and cysteine) to determine whether these amino acids are exposed to the external or internal solution, and what roles they play in gating or permeation. The behavior of single H+ channels (which have not been detected previously) will be explored using several types of noise analysis as well as by direct measurement. Demonstration that H+ current fluctuations result from stochastic gating of H+ channels will provide strong evidence that the molecule is an ion channel rather than a carrier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “amantadine” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for amantadine in the PubMed Central database: •
Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium. by Burlington DB, Meiklejohn G, Mostow SR.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182013
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Comparative activity of amantadine and ribavirin against influenza virus in vitro: possible clinical relevance. by Browne MJ, Moss MY, Boyd MR.; 1983 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184681
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Comparative single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults. by Hayden FG, Minocha A, Spyker DA, Hoffman HE.; 1985 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180222
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Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults. by Hayden FG, Gwaltney JM Jr, Van de Castle RL, Adams KF, Giordani B.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181399
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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Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics. by Hayden FG, Hoffman HE, Spyker DA.; 1983 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184669
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Inhibition of dengue virus replication by amantadine hydrochloride. by Koff WC, Elm JL Jr, Halstead SB.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283951
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Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block. by Wang C, Takeuchi K, Pinto LH, Lamb RA.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237962
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Isolation of Amantadine-Resistant Influenza A Viruses (H3N2) from Patients following Administration of Amantadine in Japan. by Iwahashi J, Tsuji K, Ishibashi T, Kajiwara J, Imamura Y, Mori R, Hara K, Kashiwagi T, Ohtsu Y, Hamada N, Maeda H, Toyoda M, Toyoda T.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87992
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Mode of Action of the Antiviral Activity of Amantadine in Tissue Culture. by Hoffmann CE, Neumayer EM, Haff RF, Goldsby RA.; 1965 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=315701
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Protective efficacy of low-dose amantadine in adults challenged with wild-type influenza A virus. by Sears SD, Clements ML.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174973
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Susceptibility of influenza A viruses to amantadine is influenced by the gene coding for M protein. by Lubeck MD, Schulman JL, Palese P.; 1978 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=354323
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 amantadine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “amantadine” (or 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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synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for amantadine (hyperlinks lead to article summaries): •
A conserved basic loop in hepatitis C virus p7 protein is required for amantadinesensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. Author(s): Griffin SD, Harvey R, Clarke DS, Barclay WS, Harris M, Rowlands DJ. Source: The Journal of General Virology. 2004 February; 85(Pt 2): 451-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769903
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A pilot study of the beneficial effects of amantadine in the treatment of painful diabetic peripheral neuropathy. Author(s): Amin P, Sturrock ND. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 February; 20(2): 114-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581262
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A randomized controlled trial of amantadine plus interferon-alpha2a vs. interferonalpha2a alone in naive patients with chronic hepatitis C randomized according to the early virological response to interferon-alpha2a monotherapy. Author(s): Angelico M, Cepparulo M, Angelico F, Francioso S, Barlattani A, Di Candilo F, Della Vecchia R, Demelia L, De Sanctis G, Gentile S, Grieco A, Parruti G, Sabusco G, Tarquini L, Tosti A, Zaru S; THE SMIEC 1 GROUP. Source: Alimentary Pharmacology & Therapeutics. 2004 February 1; 19(3): 339-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984381
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A randomized trial of amantadine and interferon versus interferon alone as initial treatment for chronic hepatitis C. Author(s): Mangia A, Minerva N, Annese M, Leandro G, Villani MR, Santoro R, Carretta V, Bacca D, Giangaspero A, Bisceglia M, Ventrella F, Dell'Erba G, Andriulli A. Source: Hepatology (Baltimore, Md.). 2001 April; 33(4): 989-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11283865
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A randomized trial of amantadine in Huntington disease. Author(s): O'Suilleabhain P, Dewey RB Jr. Source: Archives of Neurology. 2003 July; 60(7): 996-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873857
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A randomized, double-blind controlled trial of interferon alpha-2b and ribavirin vs. interferon alpha-2b and amantadine for treatment of chronic hepatitis C nonresponder to interferon monotherapy. Author(s): Younossi ZM, Mullen KD, Zakko W, Hodnick S, Brand E, Barnes DS, Carey WD, McCullough AC, Easley K, Boparai N, Gramlich T. Source: Journal of Hepatology. 2001 January; 34(1): 128-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11211889
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A randomized, double-blind, placebo-controlled trial of interferon-alpha and amantadine versus interferon-alpha alone in the treatment of patients with chronic hepatitis C. Author(s): Ahmad J, Vargas H, Balan V, Rakela J, Shakil AO. Source: Digestive Diseases and Sciences. 2002 July; 47(7): 1655-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12141832
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A screening trial of amantadine as a medication for cocaine dependence. Author(s): Shoptaw S, Kintaudi PC, Charuvastra C, Ling W. Source: Drug and Alcohol Dependence. 2002 May 1; 66(3): 217-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12062456
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Amantadine and rimantadine for preventing and treating influenza A in adults. Author(s): Jefferson TO, Demicheli V, Deeks JJ, Rivetti D. Source: Cochrane Database Syst Rev. 2002; (3): Cd001169. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137620
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Amantadine as augmentation therapy in the management of treatment-resistant depression. Author(s): Stryjer R, Strous RD, Shaked G, Bar F, Feldman B, Kotler M, Polak L, Rosenzcwaig S, Weizman A. Source: International Clinical Psychopharmacology. 2003 March; 18(2): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598820
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Amantadine for chronic hepatitis c: a magic bullet or yet another dead duck? Author(s): Craxi A, Lo Lacono O. Source: Journal of Hepatology. 2001 October; 35(4): 527-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682040
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Amantadine for chronic hepatitis C: pilot study in 14 patients. Author(s): Andant C, Lamoril J, Deybach JC, Jouet P, Soule JC. Source: European Journal of Gastroenterology & Hepatology. 2000 December; 12(12): 1319-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11192321
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Amantadine for dyskinesia in Parkinson's disease. Author(s): Crosby NJ, Deane KH, Clarke CE. Source: Cochrane Database Syst Rev. 2003; (2): Cd003467. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804468
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Amantadine for executive dysfunction syndrome in patients with dementia. Author(s): Drayton SJ, Davies K, Steinberg M, Leroi I, Rosenblatt A, Lyketsos CG. Source: Psychosomatics. 2004 May-June; 45(3): 205-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123844
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Amantadine for fatigue in multiple sclerosis. Author(s): Taus C, Giuliani G, Pucci E, D'Amico R, Solari A. Source: Cochrane Database Syst Rev. 2003; (2): Cd002818. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804439
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Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial. Author(s): Dietrich DE, Bode L, Spannhuth CW, Lau T, Huber TJ, Brodhun B, Ludwig H, Emrich HM. Source: Bipolar Disorders. 2000 March; 2(1): 65-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11254023
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Amantadine in Huntington's disease: open-label video-blinded study. Author(s): Lucetti C, Gambaccini G, Bernardini S, Dell'Agnello G, Petrozzi L, Rossi G, Bonuccelli U. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 September; 23 Suppl 2: S83-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548355
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Amantadine in Parkinson's disease. Author(s): Crosby N, Deane KH, Clarke CE. Source: Cochrane Database Syst Rev. 2003; (1): Cd003468. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535476
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Amantadine penetration into cerebrospinal fluid of a child with influenza A encephalitis. Author(s): Geskey JM, Thomas NJ. Source: The Pediatric Infectious Disease Journal. 2004 March; 23(3): 270-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014309
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Amantadine sulfate infusion effect on N30 somatosensory evoked potentials in Parkinson's disease. Author(s): Bostantjopoulou S, Katsarou Z, Georgiadis G, Zafiriou D, Kazis A. Source: Clinical Neuropharmacology. 2002 March-April; 25(2): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981240
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Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial. Author(s): Giacino JT, Whyte J. Source: The Journal of Head Trauma Rehabilitation. 2003 January-February; 18(1): 4-5; Author Reply 5-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809123
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Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial. Author(s): Meythaler JM, Brunner RC, Johnson A, Novack TA. Source: The Journal of Head Trauma Rehabilitation. 2002 August; 17(4): 300-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12105999
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Amantadine treatment in cerebellar ataxia. Author(s): Sareen D, Kumar V. Source: J Assoc Physicians India. 2001 March; 49: 382. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291986
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Amantadine treatment of psychotropic-induced weight gain in children and adolescents: case series. Author(s): Gracious BL, Krysiak TE, Youngstrom EA. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Fall; 12(3): 249-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12427299
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Amantadine: a different approach. Author(s): Torre F, Picciotto A. Source: Journal of Hepatology. 2002 May; 36(5): 705. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983458
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Amantadine-induced cortical myoclonus. Author(s): Matsunaga K, Uozumi T, Qingrui L, Hashimoto T, Tsuji S. Source: Neurology. 2001 January 23; 56(2): 279-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11160978
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Amantadine-induced multiple spike waves on an electroencephalogram of a schizophrenic patient. Author(s): Ohta K, Matsushima E, Matsuura M, Toru M, Kojima T. Source: World J Biol Psychiatry. 2000 January; 1(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611370
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Amantadine-resistant influenza A virus in Taiwan. Author(s): Shih SR, Lee CN, Tsai HR, Chen GW, Tsao KC. Source: J Formos Med Assoc. 2001 September; 100(9): 608-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11695276
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An amantadine hydrochloride dosing program adjusted for renal function during an influenza outbreak in elderly institutionalized patients. Author(s): Kolbe F, Sitar DS, Papaioannou A, Campbell G. Source: Can J Clin Pharmacol. 2003 Fall; 10(3): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506511
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Antiviral activity of amantadine in elderly patients with chronic hepatitis C. Author(s): Torre F, Campo N, Giusto R, Ansaldi F, Icardi GC, Picciotto A. Source: Gerontology. 2001 November-December; 47(6): 330-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721147
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Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease. Author(s): Luginger E, Wenning GK, Bosch S, Poewe W. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2000 September; 15(5): 873-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11009193
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Binding of amantadine to red blood cells. Author(s): Daugirdas JT, Ing IL, Cheng PJ, Wu MJ, Klawans HL, Soung LS. Source: Therapeutic Drug Monitoring. 1984; 6(4): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6515702
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Breakthrough panic after amantadine treatment in a Parkinson's disease patient. Author(s): Noveske FG. Source: The Journal of Clinical Psychiatry. 1996 August; 57(8): 374. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8752025
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Bromocriptine and amantadine in cocaine detoxification. Author(s): Giannini AJ, Folts DJ, Feather JN, Sullivan BS. Source: Psychiatry Research. 1989 July; 29(1): 11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2672061
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Bromocriptine blood levels after the concomitant administration of levodopa, amantadine and biperiden in Parkinson's disease. Author(s): Rabey JM, Oberman Z, Scharf M, Isakov M, Bar M, Graff E. Source: Acta Neurologica Scandinavica. 1990 May; 81(5): 411-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2375243
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Bronchitis and amantadine hydrochloride. Author(s): Wilson RJ. Source: The Medical Journal of Australia. 1971 June 12; 1(24): 1296. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5565160
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Bupropion-amantadine-associated neurotoxicity. Author(s): Trappler B, Miyashiro AM. Source: The Journal of Clinical Psychiatry. 2000 January; 61(1): 61-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695649
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Can patients with chronic neuropathic pain be cured by acute administration of the NMDA receptor antagonist amantadine? Author(s): Eisenberg E, Pud D. Source: Pain. 1998 February; 74(2-3): 337-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9520249
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Case series: amantadine open-label treatment of impulsive and aggressive behavior in hospitalized children with developmental disabilities. Author(s): King BH, Wright DM, Snape M, Dourish CT. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 June; 40(6): 654-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11392342
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Cerebellar dysfunction in chronic toluene abuse: beneficial response to amantadine hydrochloride. Author(s): Deleu D, Hanssens Y. Source: Journal of Toxicology. Clinical Toxicology. 2000; 38(1): 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10696922
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Changes in symptoms and plasma homovanillic acid with amantadine hydrochloride in chronic schizophrenia. Author(s): Yamada K, Kanba S, Ohnishi K, Ashikari I, Yagi G, Asai M. Source: Biological Psychiatry. 1997 May 15; 41(10): 1062-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9129786
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Changes in visual evoked potentials in patients with multiple sclerosis treated with isoprinosine and amantadine. Author(s): Maciejek Z. Source: Arch Immunol Ther Exp (Warsz). 1989; 37(5-6): 621-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2484835
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Chronic hepatitis C patients with a post-treatment virological relapse re-treated with an induction dose of 18 MU interferon-alpha in combination with ribavirin and amantadine: a two-arm randomized pilot study. Author(s): Weegink CJ, Sentjens RE, Beld MG, Dijkgraaf MG, Reesink HW. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 174-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753335
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Chronic tobacco smoking and gender as variables affecting amantadine disposition in healthy subjects. Author(s): Wong LT, Sitar DS, Aoki FY. Source: British Journal of Clinical Pharmacology. 1995 January; 39(1): 81-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7756105
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Clinical evaluation of amantadine and haloperidol in Huntington's chorea. Author(s): Saran BM, Klein MS, Benay EM. Source: The Journal of Clinical Psychiatry. 1980 June; 41(6): 221. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6445900
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Clinical pharmacokinetics of amantadine hydrochloride. Author(s): Aoki FY, Sitar DS. Source: Clinical Pharmacokinetics. 1988 January; 14(1): 35-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3280212
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Clinical trial with amantadine and pemoline in elderly patients. Author(s): Montanari C, Vallecorsi GF, Bavazzano A, D'Ayalavalva G, Sanesi P. Source: Age and Ageing. 1976 February; 5(1): 6-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=769506
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Clinical use of amantadine in brain injury rehabilitation. Author(s): Nickels JL, Schneider WN, Dombovy ML, Wong TM. Source: Brain Injury : [bi]. 1994 November-December; 8(8): 709-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7849690
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Cochrane reviews and systematic reviews of economic evaluations. Amantadine and rimantadine in the prevention and treatment of influenza. Author(s): Jefferson T, Demicheli V, Rivetti D, Deeks J. Source: Pharmacoeconomics. 1999; 16 Suppl 1: 85-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10623381
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Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo-controlled study. Author(s): Schneider WN, Drew-Cates J, Wong TM, Dombovy ML. Source: Brain Injury : [bi]. 1999 November; 13(11): 863-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10579658
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Color vision in Parkinson's disease: missing influence of amantadine sulphate. Author(s): Buttner T, Kuhn W, Muller T, Patzold T, Przuntek H. Source: Clinical Neuropharmacology. 1995 October; 18(5): 458-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8665560
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Combination of interferon alfa-2a and amantadine does not improve the efficacy of interferon therapy in patients with chronic hepatitis C. Author(s): Yang SS, Tu TC, Wu CH, Chen DS. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1575-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571789
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Combination therapy with interferon-alpha(2b), ribavirin, and amantadine in chronic hepatitis C nonresponders to interferon and ribavirin. Author(s): Thuluvath PJ, Pande H, Maygers J. Source: Digestive Diseases and Sciences. 2003 March; 48(3): 594-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757175
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Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Author(s): Englund JA, Champlin RE, Wyde PR, Kantarjian H, Atmar RL, Tarrand J, Yousuf H, Regnery H, Klimov AI, Cox NJ, Whimbey E. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 June; 26(6): 1418-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636873
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Comparative clinical and laboratory evaluation of the prophylactic capacity of ribavirin, amantadine hydrochloride, and placebo in induced human influenza type A. Author(s): Cohen A, Togo Y, Khakoo R, Waldman R, Sigel M. Source: The Journal of Infectious Diseases. 1976 June; 133 Suppl: A114-120. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=778307
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Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults. Author(s): Hayden FG, Gwaltney JM Jr, Van de Castle RL, Adams KF, Giordani B. Source: Antimicrobial Agents and Chemotherapy. 1981 February; 19(2): 226-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7347558
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Compared protective effect of nasal immunoprophylaxis using a new human monoclonal IgM antibody, human polyclonal antibodies, F(ab')2, amantadine, and zanamivir for prophylaxis of influenza A virus pneumonia in mice. Author(s): Hernandez E, Ramisse F, Lhonneux A, Noury J, Bazin H, Cavallo JD. Source: Military Medicine. 2003 March; 168(3): 246-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685693
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Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. Author(s): Weddington WW Jr, Brown BS, Haertzen CA, Hess JM, Mahaffey JR, Kolar AF, Jaffe JH. Source: The American Journal of Drug and Alcohol Abuse. 1991 June; 17(2): 137-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1862788
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Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. Author(s): Weddington WW, Brown BS, Haertzen CA, Hess JM, Kolar AF, Mahaffey JR. Source: Nida Res Monogr. 1989; 95: 483-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2701321
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Comparison of amantadine and rimantadine for prevention of type A (Russian) influenza. Author(s): Quarles JM, Couch RB, Cate TR, Goswick CB. Source: Antiviral Research. 1981 September; 1(3): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7337431
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Comparison of benztropine mesylate and amantadine HCl in neuroleptic-induced extrapyramidal symptoms. Author(s): Stenson RL, Donion PT, Meyer JE. Source: Comprehensive Psychiatry. 1976 November-December; 17(6): 763-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=791573
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Comparison of central nervous system adverse effects of amantadine and rimantadine used as sequential prophylaxis of influenza A in elderly nursing home patients. Author(s): Keyser LA, Karl M, Nafziger AN, Bertino JS Jr. Source: Archives of Internal Medicine. 2000 May 22; 160(10): 1485-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10826462
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Comparison of pharmacokinetic and safety profiles of amantadine 50- and 100-mg daily doses in elderly nursing home residents. Author(s): Somani SK, Degelau J, Cooper SL, Guay DR, Ehresman D, Zaske D. Source: Pharmacotherapy. 1991; 11(6): 460-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1771145
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Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. Author(s): Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C. Source: Journal of the Neurological Sciences. 2004 March 15; 218(1-2): 103-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759641
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Consensus on amantadine use in influenza A. Author(s): Elliott J. Source: Jama : the Journal of the American Medical Association. 1979 November 30; 242(22): 2383, 2387. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=490842
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Creutzfeldt-Jakob disease treated with amantadine. Author(s): Sanders WL. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1979 October; 42(10): 9601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=390098
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Death of a psychiatric patient from amantadine poisoning. Author(s): Simpson DM, Ramos F, Ramirez LF. Source: The American Journal of Psychiatry. 1988 February; 145(2): 267-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3341473
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Depression, Borna disease, and amantadine. Author(s): Lieb K, Hufert FT, Bechter K, Bauer J, Kornhuber J. Source: Lancet. 1997 March 29; 349(9056): 958. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9093281
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Desipramine and amantadine causing false-positive urine test for amphetamine. Author(s): Merigian KS, Browning RG. Source: Annals of Emergency Medicine. 1993 December; 22(12): 1927-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8239121
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Desipramine, amantadine, or fluoxetine in buprenorphine-maintained cocaine users. Author(s): Oliveto A, Kosten TR, Schottenfeld R, Falcioni J, Ziedonis D. Source: Journal of Substance Abuse Treatment. 1995 November-December; 12(6): 423-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749726
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Detection of amantadine-resistant influenza A virus strains in nursing homes by PCR-restriction fragment length polymorphism analysis with nasopharyngeal swabs. Author(s): Saito R, Oshitani H, Masuda H, Suzuki H. Source: Journal of Clinical Microbiology. 2002 January; 40(1): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773097
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Determination of amantadine in human plasma by capillary gas chromatography using electron-capture detection following derivatization with pentafluorobenzoyl chloride. Author(s): Rakestraw D. Source: Journal of Pharmaceutical and Biomedical Analysis. 1993 August; 11(8): 699-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8257734
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Development of tolerance to the therapeutic effect of amantadine on akathisia. Author(s): Zubenko GS, Barreira P, Lipinski JF Jr. Source: Journal of Clinical Psychopharmacology. 1984 August; 4(4): 218-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6470196
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Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics. Author(s): Hayden FG, Hoffman HE, Spyker DA. Source: Antimicrobial Agents and Chemotherapy. 1983 March; 23(3): 458-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6847173
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Differential effect of amantadine hydrochloride on the systemic and local immune response to influenza A. Author(s): Reuman PD, Bernstein DI, Keely SP, Young EC, Sherwood JR, Schiff GM. Source: Journal of Medical Virology. 1989 February; 27(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2921600
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Double blind study using amantadine hydrochloride in the therapy of Parkinson's disease. Author(s): Silver DE, Sahs AL. Source: Trans Am Neurol Assoc. 1971; 96: 307-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4945919
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Double-blind comparison of amantadine and bromocriptine for ambulatory withdrawal from cocaine dependence. Author(s): Tennant FS Jr, Sagherian AA. Source: Archives of Internal Medicine. 1987 January; 147(1): 109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3541819
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Double-blind controlled study of central nervous system side effects of amantadine, rimantadine, and chlorpheniramine. Author(s): Millet VM, Dreisbach M, Bryson YJ. Source: Antimicrobial Agents and Chemotherapy. 1982 January; 21(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7044294
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Double-blind evaluation of the effect of acute amantadine on cocaine craving. Author(s): Gawin FH, Morgan C, Kosten TR, Kleber HD. Source: Psychopharmacology. 1989; 97(3): 402-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2497490
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Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. Author(s): Cochrane Database Syst Rev. 2002;(3):CD001169 Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 June; 40(6): 658-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137620
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Duration of amantadine benefit on dyskinesia of severe Parkinson's disease. Author(s): Thomas A, Iacono D, Luciano AL, Armellino K, Di Iorio A, Onofrj M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 January; 75(1): 141-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707325
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Dystrophic effects induced by amantadine on uterine fibroleiomyomas. Author(s): Luisi M, Luisi SV. Source: American Journal of Obstetrics and Gynecology. 1982 August 15; 143(8): 975. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7102779
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Effect of add-on amantadine therapy for refractory absence epilepsy. Author(s): Shahar EM, Brand N. Source: The Journal of Pediatrics. 1992 November; 121(5 Pt 1): 819-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1432438
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Effect of amantadine (Viregyt-K) on extrapyramidal symptoms of parkinsonian patients. Author(s): Boczan G. Source: Ther Hung. 1974; 22(4): 147-53. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4465958
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Effect of amantadine hydrochloride on symptoms of frontal lobe dysfunction in brain injury: case studies and review. Author(s): Kraus MF, Maki PM. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1997 Spring; 9(2): 222-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9144101
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Effect of amantadine on drug-induced parkisonism: relationship between plasma levels and effect. Author(s): Pacifici GM, Nardini M, Ferrari P, Latini R, Fieschi C, Morselli PL. Source: British Journal of Clinical Pharmacology. 1976 October; 3(5): 883-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=788761
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Effect of amantadine on sexual dysfunction in neuroleptic-treated male schizophrenic patients. Author(s): Valevski A, Modai I, Zbarski E, Zemishlany Z, Weizman A. Source: Clinical Neuropharmacology. 1998 November-December; 21(6): 355-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9844793
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Effect of amantadine on weight gain during olanzapine treatment. Author(s): Floris M, Lejeune J, Deberdt W. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 April; 11(2): 181-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11313165
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Effect of drugs influencing central 5-hydroxytryptamine mechanisms on amantadineinduced stereotyped behaviour in the rat. Author(s): Dhavare BS, Nandal NV, Balsara JJ, Chandorkar AG. Source: Indian J Physiol Pharmacol. 1983 January-March; 27(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6682830
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Effect of L-dopa or amantadine therapy on sleep spindles in Parkinsonism. Author(s): Puca FM, Bricolo A, Turella G. Source: Electroencephalography and Clinical Neurophysiology. 1973 September; 35(3): 327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4126184
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Effect of pH on in vitro potency of amantadine against Plasmodium falciparum. Author(s): Evans SG, Havlik I. Source: The American Journal of Tropical Medicine and Hygiene. 1996 March; 54(3): 232-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8600756
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Effect of ribavirin and amantadine on early hepatitis C virus RNA rebound and clearance in serum during daily high-dose interferon. Author(s): Lake-Bakaar G, Ruffini L, Kuzmic P. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 126-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645800
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Effectiveness of amantadine in reducing relapses in multiple sclerosis. Author(s): Plaut GS. Source: Journal of the Royal Society of Medicine. 1987 February; 80(2): 91-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3550084
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Effects of alpha interferon induction plus ribavirin with or without amantadine in the treatment of interferon non-responsive chronic hepatitis C: a randomised trial. Author(s): Adinolfi LE, Utili R, Tonziello A, Ruggiero G. Source: Gut. 2003 May; 52(5): 701-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692056
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Effects of amantadine and L-dopa on apomorphine- and d-amphetamine-induced stereotyped behaviour in rats. Author(s): Cox B, Tha SJ. Source: European Journal of Pharmacology. 1973 October; 24(1): 96-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4796449
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Effects of amantadine and trihexyphenidyl on memory in elderly normal volunteers. Author(s): McEvoy JP, McCue M, Spring B, Mohs RC, Lavori PW, Farr RM. Source: The American Journal of Psychiatry. 1987 May; 144(5): 573-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3578566
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Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson's disease. Author(s): Wandinger KP, Hagenah JM, Kluter H, Rothermundt M, Peters M, Vieregge P. Source: Journal of Neuroimmunology. 1999 August 3; 98(2): 214-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430055
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Effects of biperiden and amantadine on memory in medicated chronic schizophrenic patients. A Double-blind cross-over study. Author(s): Silver H, Geraisy N. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1995 February; 166(2): 241-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7728369
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Effects of chronic amantadine hydrochloride ingestion on its and acetaminophen pharmacokinetics in young adults. Author(s): Aoki FY, Sitar DS. Source: Journal of Clinical Pharmacology. 1992 January; 32(1): 24-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1740533
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Effects of L-histidine and promethazine on apomorphine and amantadine stereotypy in rats. Author(s): Balsara JJ, Dhavare BS, Nandal NV, Chandorkar AG. Source: Psychopharmacology. 1983; 79(4): 372-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6407056
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Effects of long-term amantadine treatment on clinical symptoms and EEG of a patient in a vegetative state. Author(s): Horiguchi J, Inami Y, Shoda T. Source: Clinical Neuropharmacology. 1990 February; 13(1): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2306751
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Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy: results of a preliminary study. Author(s): Snijdelaar DG, Koren G, Katz J. Source: Anesthesiology. 2004 January; 100(1): 134-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695734
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Efficacy and safety of low dosage amantadine hydrochloride as prophylaxis for influenza A. Author(s): Reuman PD, Bernstein DI, Keefer MC, Young EC, Sherwood JR, Schiff GM. Source: Antiviral Research. 1989 February; 11(1): 27-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2712549
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Efficacy of amantadine hydrochloride in patients with chronic hepatitis C. Author(s): Nakamura H. Source: Journal of Gastroenterology. 2001 November; 36(11): 792-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757755
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Emergence and possible transmission of amantadine-resistant viruses during nursing home outbreaks of influenza A (H3N2). Author(s): Mast EE, Harmon MW, Gravenstein S, Wu SP, Arden NH, Circo R, Tyszka G, Kendal AP, Davis JP. Source: American Journal of Epidemiology. 1991 November 1; 134(9): 988-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1951297
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Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine. Author(s): Hayden FG, Hay AJ. Source: Curr Top Microbiol Immunol. 1992; 176: 119-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1600749
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Emergence of amantadine-resistant influenza A viruses: epidemiological study. Author(s): Suzuki H, Saito R, Masuda H, Oshitani H, Sato M, Sato I. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 September; 9(3): 195-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513385
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Evaluation of amantadine in the prophylaxis of influenza A (H1N1) virus infection: a controlled field trial among young adults and high-risk patients. Author(s): Pettersson RF, Hellstrom PE, Penttinen K, Pyhala R, Tokola O, Vartio T, Visakorpi R. Source: The Journal of Infectious Diseases. 1980 September; 142(3): 377-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7003032
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Evaluation of the safety of amantadine-HC1 and the role of respiratory viral infections in children with cystic fibrosis. Author(s): Wright PF, Khaw KT, Oxman MN, Shwachman H. Source: The Journal of Infectious Diseases. 1976 August; 134(2): 144-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=787443
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Exacerbation of schizophrenia associated with amantadine. Author(s): Nestelbaum Z, Siris SG, Rifkin A, Klar H, Reardon GT. Source: The American Journal of Psychiatry. 1986 September; 143(9): 1170-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2875665
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Excess amantadine use and resistant viruses. Author(s): Suzuki H, Saito R, Oshitani H. Source: Lancet. 2001 December 1; 358(9296): 1910. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11741673
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Failed fertilization during an in vitro fertilization cycle after oral ingestion of amantadine hydrochloride. Author(s): Cowan BD, Lucas JA 3rd, Sopelak VM, Lockard V. Source: J in Vitro Fert Embryo Transf. 1988 October; 5(5): 282-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3148023
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Failure of amantadine and bromocriptine to counteract alcoholic inebriation in man. Author(s): Nuotto E, Mattila MJ. Source: Acta Pharmacol Toxicol (Copenh). 1984 September; 55(3): 168-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6507109
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Failure of amantadine to modify serum growth hormone and insulin levels. Author(s): Cavagnini F, Pontiroli AE, Raggi U, Peracchi M, Malinverni A. Source: Experientia. 1973 May 15; 29(5): 573. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4730294
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Fatal overdose with amantadine. Author(s): Cook PE, Dermer SW, McGurk T. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1986 November; 31(8): 757-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3791133
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Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo. Author(s): Krupp LB, Coyle PK, Doscher C, Miller A, Cross AH, Jandorf L, Halper J, Johnson B, Morgante L, Grimson R. Source: Neurology. 1995 November; 45(11): 1956-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7501140
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Favorable outcome after treatment with amantadine and ribavirin in a pregnancy complicated by influenza pneumonia. A case report. Author(s): Kirshon B, Faro S, Zurawin RK, Samo TC, Carpenter RJ. Source: J Reprod Med. 1988 April; 33(4): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3367344
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Fentanyl-induced muscle rigidity as affected by pretreatment with amantadine hydrochloride. Author(s): Vacanti CA, Silbert BS, Vacanti FX. Source: Journal of Clinical Anesthesia. 1992 July-August; 4(4): 282-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1419008
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Fetal outcome following intrauterine amantadine exposure. Author(s): Levy M, Pastuszak A, Koren G. Source: Reproductive Toxicology (Elmsford, N.Y.). 1991; 5(1): 79-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1807540
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Fotosensitization by Amantadine (Symmetrel). Author(s): van Ketel WG, Goedhart-van Dijk B. Source: Dermatologica. 1974; 148(2): 124-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4837658
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Four-year treatment of patients with parkinsonism using amantadine alone or with levodopa. Author(s): Timberlake WH, Vance MA. Source: Annals of Neurology. 1978 February; 3(2): 119-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=350129
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Frequency of amantadine-resistant influenza A viruses during two seasons featuring cocirculation of H1N1 and H3N2. Author(s): Saito R, Sakai T, Sato I, Sano Y, Oshitani H, Sato M, Suzuki H. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2164-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734269
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From the National Institutes of Health. Report of a workshop on clinical studies of the efficacy of amantadine and rimantadine against influenza vireus. Author(s): LaMontagne JR, Galasso GJ. Source: The Journal of Infectious Diseases. 1978 December; 138(6): 928-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=368266
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Gas chromatographic determination of amantadine hydrochloride (Symmetrel) in human plasma and urine. Author(s): Sioufi A, Pommier F. Source: Journal of Chromatography. 1980 July 11; 183(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7400262
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Gas-chromatographic determination of amantadine in human urine. Author(s): Stumph MJ, Noall MW, Knight V. Source: Clinical Chemistry. 1980 February; 26(2): 295-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7353280
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Gas-liquid chromatographic determination of plasma and urinary levels of amantadine in man. Author(s): Belanger PM, Grech-Belanger O. Source: Journal of Chromatography. 1982 March 12; 228: 327-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7076756
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Gender and age as factors in the inhibition of renal clearance of amantadine by quinine and quinidine. Author(s): Gaudry SE, Sitar DS, Smyth DD, McKenzie JK, Aoki FY. Source: Clinical Pharmacology and Therapeutics. 1993 July; 54(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8330461
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Glutamatergic dysfunction in catatonia? Successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine. Author(s): Northoff G, Eckert J, Fritze J. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1997 April; 62(4): 404-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9120462
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Habituation of blink reflexes in parkinsonian patients under levodopa and amantadine treatment. Author(s): Messina C, Di Rosa AE, Tomasello F. Source: Journal of the Neurological Sciences. 1972 October; 17(2): 141-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4340932
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HCV RNA levels during therapy with amantadine in addition to interferon and ribavirin in chronic hepatitis C patients with previous nonresponse or response/relapse to interferon and ribavirin. Author(s): Carlsson T, Lindahl K, Schvarcz R, Wejstal R, Uhnoo I, Shev S, Reichard O. Source: Journal of Viral Hepatitis. 2000 November; 7(6): 409-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115051
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High frequency of resistant viruses harboring different mutations in amantadinetreated children with influenza. Author(s): Shiraishi K, Mitamura K, Sakai-Tagawa Y, Goto H, Sugaya N, Kawaoka Y. Source: The Journal of Infectious Diseases. 2003 July 1; 188(1): 57-61. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825171
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High-dose interferon alpha-2a with ribavirin and amantadine in naive chronic hepatitis C patients--results of a randomized, prospective, pilot study. Author(s): Ullerich H, Avenhaus W, Poremba C, Domschke W, Menzel J. Source: Alimentary Pharmacology & Therapeutics. 2002 December; 16(12): 2107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452944
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High-performance liquid chromatographic determination of amantadine in urine after micelle-mediated pre-column derivatization with 1-fluoro-2,4-dinitrobenzene. Author(s): van der Horst FA, Teeuwsen J, Holthuis JJ, Brinkman UA. Source: Journal of Pharmaceutical and Biomedical Analysis. 1990; 8(8-12): 799-804. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2100626
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Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Author(s): Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H. Source: Molecular Pharmacology. 1998 August; 54(2): 342-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9687576
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Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Author(s): Verhagen Metman L, Morris MJ, Farmer C, Gillespie M, Mosby K, Wuu J, Chase TN. Source: Neurology. 2002 September 10; 59(5): 694-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221159
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Hyponatraemia due to amantadine hydrochloride and L-dopa/carbidopa. Author(s): Lammers GJ, Roos RA. Source: Lancet. 1993 August 14; 342(8868): 439. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8101938
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Implications of viral resistance to amantadine in control of influenza A. Author(s): Monto AS, Arden NH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1992 August; 15(2): 362-7; Discussion 368-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1520770
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Improvements in activity and appetite among long-term care patients treated with amantadine. A clinical report. Author(s): Roca RP, Santmyer K, Gloth FM, Denman SJ. Source: Journal of the American Geriatrics Society. 1990 June; 38(6): 675-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2113547
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In vitro effect of amantadine and interferon alpha-2a on hepatitis C virus markers in cultured peripheral blood mononuclear cells from hepatitis C virus-infected patients. Author(s): Martin J, Navas S, Fernandez M, Rico M, Pardo M, Quiroga JA, Zahm F, Carreno V. Source: Antiviral Research. 1999 May; 42(1): 59-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333143
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Incidence of amantadine-resistant influenza A viruses in sentinel surveillance sites and nursing homes in Niigata, Japan. Author(s): Masuda H, Suzuki H, Oshitani H, Saito R, Kawasaki S, Nishikawa M, Satoh H. Source: Microbiology and Immunology. 2000; 44(10): 833-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128067
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Indications for amantadine in otherwise healthy children. Author(s): Glezen WP. Source: The Pediatric Infectious Disease Journal. 1993 January; 12(1): 106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8417417
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Induction of the platelet release reaction by concanavalin A-relation of con A binding to release and modification of release by ATP, PGE1 and amantadine. Author(s): Schmukler M, Zieve PD, Jewett PB. Source: Biochemical Pharmacology. 1976 August 15; 25(16): 1819-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=962960
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Influenza A outbreak in a nursing home: the value of early diagnosis and the use of amantadine hydrochloride. Author(s): Staynor K, Foster G, McArthur M, McGeer A, Petric M, Simor AE. Source: Can J Infect Control. 1994 Winter; 9(4): 109-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7766913
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Influenza, influenza vaccine, and amantadine/rimantadine. Author(s): Zimmerman RK, Ruben FL, Ahwesh ER. Source: The Journal of Family Practice. 1997 August; 45(2): 107-22; Quiz 123-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9267368
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Influenza: vaccines or amantadine? Author(s): Chanin A. Source: Jama : the Journal of the American Medical Association. 1977 April 4; 237(14): 1445. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=576634
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Inhibition of dengue virus replication by amantadine hydrochloride. Author(s): Koff WC, Elm JL Jr, Halstead SB. Source: Antimicrobial Agents and Chemotherapy. 1980 July; 18(1): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7416739
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Intense and recurrent deja vu experiences related to amantadine and phenylpropanolamine in a healthy male. Author(s): Taiminen T, Jaaskelainen SK. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2001 September; 8(5): 460-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535020
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Interaction of apomorphine and amantadine with ethanol in men. Author(s): Alkana RL, Parker ES, Malcolm RD, Cohen HB, Birch H, Noble EP. Source: Alcoholism, Clinical and Experimental Research. 1982 Summer; 6(3): 403-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6751137
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Interaction of the antivirus agents remantadine and amantadine with lipid membranes and the influence on the curvature of human red cells. Author(s): Tverdislov VA, el-Karadagi S, Kharitonenkov IG, Glaser R, Donath E, Herrmann A, Lentzsch P, Donath J. Source: Gen Physiol Biophys. 1986 February; 5(1): 61-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3021565
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Interactions of L-dopa and amantadine in patients with Parkinsonism. Author(s): Cox B, Danta G, Schnieden H, Yuill GM. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1973 June; 36(3): 354-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4714097
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Interferon alfa2a induction therapy in combination with ribavirin and amantadine for the treatment of naive patients with chronic HCV infection. Author(s): Engler S, Flechtenmacher C, Wiedemann KH, Gugler R, Stremmel W, Kallinowski B. Source: Journal of Viral Hepatitis. 2004 January; 11(1): 60-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738559
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Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients. Author(s): Tabone M, Laudi C, Delmastro B, Biglino A, Andreoni M, Chieppa F, Bonardi R, Cariti G, Cusumano S, Brunello F, Calleri G, Manca A, Della Monica P, Sidoli L, Rizzetto M, Pera A. Source: Journal of Hepatology. 2001 October; 35(4): 517-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682037
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Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial. Author(s): Helbling B, Stamenic I, Viani F, Gonvers JJ, Dufour JF, Reichen J, Cathomas G, Steuerwald M, Borovicka J, Sagmeister M, Renner EL; Investigators of the Swiss Association for the Study of the Liver. Source: Hepatology (Baltimore, Md.). 2002 February; 35(2): 447-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826422
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Interferon and ribavirin versus interferon and amantadine in interferon nonresponders with chronic hepatitis C. Author(s): Khalili M, Denham C, Perrillo R. Source: The American Journal of Gastroenterology. 2000 May; 95(5): 1284-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10811340
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Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: a UK multicentre study. Author(s): Caronia S, Bassendine MF, Barry R, Mills P, Naoumov NV, Fox R, Lowes J, Hollanders D, Murray-Lyon L, Irving WL, Goldin RD, Foster GR; UK Amantadine Study Group. Source: Journal of Hepatology. 2001 October; 35(4): 512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682036
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Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study. Author(s): Gaeta GB, Stornaiuolo G, Stanzione M, Ascione T, Pasquazzi C, Taliani G, Cimino L, Budillon G, Piccinino F. Source: Journal of Viral Hepatitis. 2001 July; 8(4): 284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454180
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Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study. Author(s): Andreone P, Gramenzi A, Cursaro C, Biselli M, Di Giammarino L, Grazi GL, Jovine E, D'Errico A, Galli S, Mazziotti A, Cavallari A, Bernardi M. Source: Dig Liver Dis. 2001 November; 33(8): 693-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11785716
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Intermittent amantadine for fluoxetine-induced anorgasmia. Author(s): Balon R. Source: Journal of Sex & Marital Therapy. 1996 Winter; 22(4): 290-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9018655
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Intravenous amantadine improves levadopa-induced dyskinesias: an acute doubleblind placebo-controlled study. Author(s): Del Dotto P, Pavese N, Gambaccini G, Bernardini S, Metman LV, Chase TN, Bonuccelli U. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2001 May; 16(3): 515-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391748
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Intravenous amantadine sulphate application improves the performance of complex but not simple motor tasks in patients with Parkinson's disease. Author(s): Muller T, Kuhn W, Schulte T, Przuntek H. Source: Neuroscience Letters. 2003 March 13; 339(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618292
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Intravenous application of amantadine and antiparkinsonian efficacy in Parkinsonian patients. Author(s): Muller T, Kuhn W, Quack G, Przuntek H. Source: Journal of Neural Transmission. Supplementum. 1995; 46: 407-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8821076
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Intravenous lidocaine, amantadine, and placebo in the treatment of sciatica: a doubleblind, randomized, controlled study. Author(s): Medrik-Goldberg T, Lifschitz D, Pud D, Adler R, Eisenberg E. Source: Regional Anesthesia and Pain Medicine. 1999 November-December; 24(6): 53440. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588558
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Investigation of far red dyes for use in peroxyoxalate chemiluminescence detection and analysis of the cy5 derivative of amantadine hydrochloride in human plasma. Author(s): Ellingson A, Karnes HT. Source: Biomedical Chromatography : Bmc. 1998 January-February; 12(1): 8-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9470967
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Isolation of amantadine-resistant influenza a viruses (H3N2) from patients following administration of amantadine in Japan. Author(s): Iwahashi J, Tsuji K, Ishibashi T, Kajiwara J, Imamura Y, Mori R, Hara K, Kashiwagi T, Ohtsu Y, Hamada N, Maeda H, Toyoda M, Toyoda T. Source: Journal of Clinical Microbiology. 2001 April; 39(4): 1652-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11283109
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IV amantadine improves chorea in Huntington's disease: an acute randomized, controlled study. Author(s): Lucetti C, Del Dotto P, Gambaccini G, Dell' Agnello G, Bernardini S, Rossi G, Murri L, Bonuccelli U. Source: Neurology. 2003 June 24; 60(12): 1995-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821751
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Jakob-Creutzfeldt disease: treatment by amantadine. Author(s): Braham J. Source: British Medical Journal. 1971 October 23; 4(781): 212-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4940159
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Lack of antiviral effect of amantadine in Borna disease virus infection. Author(s): Stitz L, Planz O, Bilzer T. Source: Medical Microbiology and Immunology. 1998 March; 186(4): 195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9574902
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Latency and successive reaction time in Parkinson's disease--the effects of carbidopa and amantadine. Author(s): Sandyk R. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1981 March 21; 59(13): 441. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7209720
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L-dopa and amantadine hydrochloride in extra-pyramidal disorders. Author(s): Parkes JD, Knill-Jones RP, Clements PJ. Source: Postgraduate Medical Journal. 1971 February; 47(544): 116-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5572526
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L-dopa and amantadine hydrochloride in Parkinson's disease. Author(s): Parkes JD, Zilkha KJ, Knill-Jones RP, Clements PJ, Baxter R. Source: Int Z Klin Pharmakol Ther Toxikol. 1971 April; 4(3): 356-60. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4931417
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L-dopa and amantadine in the therapy of parkinsonism. Author(s): Weeth JB, Shealy CN, Mercier DA. Source: Wis Med J. 1969 November; 68(11): 325-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4901055
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L-dopa treatment of parkinsonism. Clinical observations on the use of amantadine hydrochloride. Author(s): Reveno WS, Bauer RB, Rosenbaum H. Source: Geriatrics. 1971 August; 26(8): 61-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5096462
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Letter: Accumulation of amantadine hydrochloride in renal insufficiency. Author(s): Ing TS, Rahn AC, Armbruster KF, Oyama JH, Klawans HL. Source: The New England Journal of Medicine. 1974 December 5; 291(23): 1257. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4419814
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Letter: Amantadine for influenza in general practice. Author(s): Chanin A. Source: Jama : the Journal of the American Medical Association. 1974 February 4; 227(5): 560. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4405811
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Letter: Amantadine in chorea. Author(s): Gray MW, Herzberg L, Lerman JA, Turnbull MJ, Victoratos G. Source: Lancet. 1975 July 19; 2(7925): 132-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=49730
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Letter: Cardiovascular maldevelopment associated with maternal exposure to amantadine. Author(s): Nora JJ, Nora AH, Way GL. Source: Lancet. 1975 September 27; 2(7935): 607. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=51431
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Levodopa and amantadine in the treatment of Parkinsonism. Author(s): Critchley E. Source: The Practitioner. 1972 April; 208(246): 499-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5031037
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Lithium induced cogwheel rigidity: treatment with amantadine. Author(s): Abrams AA, Braff DL. Source: Pharmakopsychiatr Neuropsychopharmakol. 1980 July; 13(4): 240-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7443779
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Livedo reticularis in Parkinson's disease patients treated with amantadine hydrochloride. Author(s): Silver DE, Sahs AL. Source: Neurology. 1972 July; 22(7): 665-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4673247
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Livedo reticularis in patients with parkinsonism receiving amantadine. Author(s): Shealy CN, Weeth JB, Mercier D. Source: Jama : the Journal of the American Medical Association. 1970 June 1; 212(9): 1522-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5467552
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Livedo reticularis induced by amantadine. Author(s): Sladden MJ, Nicolaou N, Johnston GA, Hutchinson PE. Source: The British Journal of Dermatology. 2003 September; 149(3): 656-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511008
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Liver function during amantadine hydrochloride medication in compensated liver disease. Author(s): Schnack H, Wewalka F, Guttmann G. Source: Int Z Klin Pharmakol Ther Toxikol. 1969 April; 2(2): 185-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5800713
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Long term amantadine treatment. The danger of withdrawal. Author(s): Wilson JA, Farquhar DL, Primrose WR, Smith RG. Source: Scott Med J. 1987 October; 32(5): 135. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3441780
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Long-term evaluation of amantadine and levodopa combination in parkinsonism by double-blind corssover analyses. Author(s): Fahn S, Isgreen WP. Source: Neurology. 1975 August; 25(8): 695-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=807869
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Long-term stability of the anti-influenza A compounds--amantadine and rimantadine. Author(s): Scholtissek C, Webster RG. Source: Antiviral Research. 1998 June; 38(3): 213-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9754890
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Long-term therapy of Parkinson's disease with amantadine, alone and combined with levodopa. Author(s): Zeldowicz LR, Hubermann J. Source: Can Med Assoc J. 1973 October 6; 109(7): 588-93. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4582563
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Managing influenza: amantadine, rimantadine and beyond. Author(s): Fleming DM. Source: Int J Clin Pract. 2001 April; 55(3): 189-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11351773
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Mania secondary to amantadine treatment of neuroleptic-induced hyperprolactinemia. Author(s): Rego MD, Giller EL Jr. Source: The Journal of Clinical Psychiatry. 1989 April; 50(4): 143-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2564388
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Mechanism of action of amantadine. Author(s): Pearce J. Source: British Medical Journal. 1971 August 26; 3(773): 529. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4327681
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Mental side effects of amantadine therapy: its spectrum and characteristics in a normal population. Author(s): Flaherty JA, Bellur SN. Source: The Journal of Clinical Psychiatry. 1981 September; 42(9): 344-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7275941
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Methadone tapering plus amantadine to detoxify heroin-dependent inpatients with or without an active cocaine use disorder: two randomised controlled trials. Author(s): Perez de los Cobos J, Duro P, Trujols J, Tejero A, Batlle F, Ribalta E, Casas M. Source: Drug and Alcohol Dependence. 2001 July 1; 63(2): 187-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11376923
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More on amantadine in tardive dyskinesia. Author(s): Crane GE. Source: The New England Journal of Medicine. 1971 November; 285(20): 1150-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5095753
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More recent lessons from amantadine. Author(s): Uitti RJ. Source: Neurology. 1999 February; 52(3): 676. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10025822
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Motor-learning impairment by amantadine in healthy volunteers. Author(s): Tahar AH, Blanchet PJ, Doyon J. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 January; 29(1): 187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532914
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N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury. Author(s): Van Reekum R, Bayley M, Garner S, Burke IM, Fawcett S, Hart A, Thompson W. Source: Brain Injury : [bi]. 1995 January; 9(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7874096
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Neuraminidase inhibitor and amantadine. Author(s): Dawson J. Source: Lancet. 2000 June 24; 355(9222): 2254. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881922
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Neuroleptic malignant syndrome and amantadine withdrawal. Author(s): Lazarus A. Source: The American Journal of Psychiatry. 1985 January; 142(1): 142. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3966578
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Neuroleptic malignant syndrome following withdrawal of amantadine in a patient with influenza A encephalopathy. Author(s): Ito T, Shibata K, Watanabe A, Akabane J. Source: European Journal of Pediatrics. 2001 June; 160(6): 401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11421428
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Neuroleptic-induced catatonia after abrupt withdrawal of amantadine during neuroleptic therapy. Author(s): Brown CS, Wittkowsky AK, Bryant SG. Source: Pharmacotherapy. 1986 July-August; 6(4): 193-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2877444
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New lessons from old drugs: amantadine and Parkinson's disease. Author(s): Goetz CG. Source: Neurology. 1998 May; 50(5): 1211-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9595964
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New use for an old drug: amantadine benefits levodopa-induced dyskinesia. Author(s): Rajput AH, Rajput A, Lang AE, Kumar R, Uitti RJ, Galvez-Jimenez N. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1998 September; 13(5): 851. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9756161
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No difference in the effect of biperiden and amantadine on negative symptoms in medicated chronic schizophrenic patients. Author(s): Silver H, Geraisy N. Source: Biological Psychiatry. 1995 September 15; 38(6): 413-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8547463
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No difference in the effect of biperiden and amantadine on parkinsonian- and tardive dyskinesia-type involuntary movements: a double-blind crossover, placebocontrolled study in medicated chronic schizophrenic patients. Author(s): Silver H, Geraisy N, Schwartz M. Source: The Journal of Clinical Psychiatry. 1995 April; 56(4): 167-70. Erratum In: J Clin Psychiatry 1995 September; 56(9): 435. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7713856
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Observations on the effect of amantadine hydrochloride in the treatment of Parkinsonism. Author(s): Schwieger AC, Jenkins AC. Source: The Medical Journal of Australia. 1970 October 3; 2(14): 630-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5477806
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Occurrence of adverse effects and high amantadine concentrations with influenza prophylaxis in the nursing home. Author(s): Degelau J, Somani S, Cooper SL, Irvine PW. Source: Journal of the American Geriatrics Society. 1990 April; 38(4): 428-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2329251
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Occurrence of amantadine- and rimantadine-resistant influenza A virus strains during the 1980 epidemic. Author(s): Heider H, Adamczyk B, Presber HW, Schroeder C, Feldblum R, Indulen MK. Source: Acta Virol. 1981 November; 25(6): 395-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6120642
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On the effect of amantadine on monoamines and their metabolites in the brain and cerebrospinal fluid. Author(s): Rinne UK, Sonninen V, Hyyppa M. Source: Experientia. 1972 January 15; 28(1): 57-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5013063
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On the synchronizing effect of amantadine-1-hydrochlorid (Symmetrel) on pathological EEG-activity. Author(s): Vardi J, Streifler M. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1975; 37(1): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1159416
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Palliative treatment of tardive dyskinesia with combination of amantadineneuroleptic administration. Author(s): Allen RM. Source: Biological Psychiatry. 1982 June; 17(6): 719-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6179548
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Persistent hiccup cured by amantadine. Author(s): Askenasy JJ, Boiangiu M, Davidovitch S. Source: The New England Journal of Medicine. 1988 March 17; 318(11): 711. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3344027
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Pharmacokinetics of amantadine hydrochloride in subjects with normal and impaired renal function. Author(s): Horadam VW, Sharp JG, Smilack JD, McAnalley BH, Garriott JC, Stephens MK, Prati RC, Brater DC. Source: Annals of Internal Medicine. 1981 April; 94(4 Pt 1): 454-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7212501
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Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. Author(s): Kosten TR, Morgan CM, Falcione J, Schottenfeld RS. Source: Archives of General Psychiatry. 1992 November; 49(11): 894-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1444728
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Pilot study of interferon-alpha high-dose induction therapy in combination with ribavirin plus amantadine for nonresponder patients with chronic hepatitis C. Author(s): Berg T, Naumann U, Wiedenmann B, Hopf U. Source: Zeitschrift Fur Gastroenterologie. 2001 February; 39(2): 145-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11253505
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Pilot study of interferon-alpha with and without amantadine for the treatment of hepatitis C in HIV coinfected individuals on antiretroviral therapy. Author(s): Sax H, Friedl A, Renner E, Steuerwald MH, Weber R; Swiss HIV Cohort Study. Source: Infection. 2001 October; 29(5): 267-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11688904
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Possible new mechanism for the antiparkinsonian effect of amantadine. Author(s): Bennett VL, Juorio AV, Li XM. Source: Journal of Psychiatry & Neuroscience : Jpn. 1999 January; 24(1): 52-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9987209
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Possible use of amantadine in depression. Author(s): Huber TJ, Dietrich DE, Emrich HM. Source: Pharmacopsychiatry. 1999 March; 32(2): 47-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333162
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Post-polio fatigue treated with amantadine. Author(s): Dunn MG. Source: Archives of Neurology. 1991 June; 48(6): 570. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2039376
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Potential of influenza vaccine and amantadine to prevent influenza A illness in Canadian forces personnel 1980-1983. Author(s): Aoki FY, Stiver HG, Sitar DS, Hammond GW, Milley EV, Vermeersch C, Hughes HE, Cooper T, Sekla L, Lamontage M, et al. Source: Military Medicine. 1986 September; 151(9): 459-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3095698
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Prevention and control of type A influenza infections in nursing homes. Benefits and costs of four approaches using vaccination and amantadine. Author(s): Patriarca PA, Arden NH, Koplan JP, Goodman RA. Source: Annals of Internal Medicine. 1987 November; 107(5): 732-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3116900
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Prevention and treatment of influenza A with amantadine hydrochloride. Author(s): Junker A, Scheifele D. Source: Can Med Assoc J. 1980 November 22; 123(10): 961-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7448670
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Prevention of influenza A/USSR/77 (H1N1): an evaluation of the side effects and efficacy of amantadine in recruits at Fort Sam Houston. Author(s): Kantor RJ, Potts DW, Stevens D, Noble GR. Source: Military Medicine. 1980 May; 145(5): 312-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6770291
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Prevention of Russian influenza by amantadine. Author(s): Monto AS, Gunn RA, Bandyk MG, King CL. Source: Jama : the Journal of the American Medical Association. 1979 March 9; 241(10): 1003-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=368354
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Prevention, management, and control of influenza. Role of amantadine. Author(s): Mostow SR. Source: The American Journal of Medicine. 1987 June 19; 82(6A): 35-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3296750
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Prolonged excretion of amantadine-resistant influenza a virus quasi species after cessation of antiviral therapy in an immunocompromised patient. Author(s): Boivin G, Goyette N, Bernatchez H. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 March 1; 34(5): E23-5. Epub 2002 January 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807683
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Prolonged shedding of amantadine-resistant influenzae A viruses by immunodeficient patients: detection by polymerase chain reaction-restriction analysis. Author(s): Klimov AI, Rocha E, Hayden FG, Shult PA, Roumillat LF, Cox NJ. Source: The Journal of Infectious Diseases. 1995 November; 172(5): 1352-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7594676
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Prophylactic use of amantadine in a boarding school outbreak of influenza A. Author(s): Davies JR, Grilli EA, Smith AJ, Hoskins TW. Source: J R Coll Gen Pract. 1988 August; 38(313): 346-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3256644
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Protective efficacy of low-dose amantadine in adults challenged with wild-type influenza A virus. Author(s): Sears SD, Clements ML. Source: Antimicrobial Agents and Chemotherapy. 1987 October; 31(10): 1470-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3435099
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Psychotic episode related to phenylpropanolamine and amantadine in a healthy female. Author(s): Stroe AE, Hall J, Amin F. Source: General Hospital Psychiatry. 1995 November; 17(6): 457-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8714809
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Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naive patients with chronic hepatitis C. Author(s): Thuluvath PJ, Maheshwari A, Mehdi J, Fairbanks KD, Wu LL, Gelrud LG, Ryan MJ, Anania FA, Lobis IF, Black M. Source: Gut. 2004 January; 53(1): 130-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684587
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Randomized, double-blind, placebo-controlled trial of interferon alfa2a with and without amantadine as initial treatment for chronic hepatitis C. Author(s): Zeuzem S, Teuber G, Naumann U, Berg T, Raedle J, Hartmann S, Hopf U. Source: Hepatology (Baltimore, Md.). 2000 October; 32(4 Pt 1): 835-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11003631
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Randomized, placebo-controlled, double-blind trial with interferon-alpha with and without amantadine sulphate in primary interferon-alpha nonresponders with chronic hepatitis C. Author(s): Teuber G, Berg T, Naumann U, Raedle J, Brinkmann S, Hopf U, Zeuzem S. Source: Journal of Viral Hepatitis. 2001 July; 8(4): 276-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454179
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Recurrent herpes simplex sciatica and its treatment with amantadine hydrochloride. Author(s): Fisher DA. Source: Cutis; Cutaneous Medicine for the Practitioner. 1982 May; 29(5): 467-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7094632
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Recurrent neuroleptic malignant syndrome due to haloperidol and amantadine. Author(s): Hermesh H, Sirota P, Eviatar J. Source: Biological Psychiatry. 1989 April 1; 25(7): 962-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2720007
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Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine. Author(s): Younkin SW, Betts RF, Roth FK, Douglas RG Jr. Source: Antimicrobial Agents and Chemotherapy. 1983 April; 23(4): 577-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6859836
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Refinement in the measurement of treatment response with combined L-dopa and amantadine in Parkinsonism. Author(s): Kravitz EA, Hollmann TD. Source: J Chronic Dis. 1974 December; 27(11-12): 563-72. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4612055
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Relapse of neuroleptic malignant syndrome with early discontinuation of amantadine therapy. Author(s): Hamburg P, Weilburg JB, Cassem NH, Cohen L, Brown S. Source: Comprehensive Psychiatry. 1986 July-August; 27(4): 272-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3731763
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Removal of amantadine hydrochloride by dialysis in patients with renal insufficiency. Author(s): Ing TS, Mahurkar SD, Dunea G, Hayashi JA, Klawans HL, Markey WS. Source: Can Med Assoc J. 1976 September 18; 115(6): 515. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=953934
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Renaissance of amantadine in the treatment of Parkinson's disease. Author(s): Blanchet PJ, Metman LV, Chase TN. Source: Adv Neurol. 2003; 91: 251-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442683
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Replacement of chronically administered anticholinergic drugs by amantadine in outpatient management of chronic schizophrenia. Author(s): McEvoy JP, McCue M, Freter S. Source: Clinical Therapeutics. 1987; 9(4): 429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2886223
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Resistance of influenza A virus to amantadine and rimantadine: results of one decade of surveillance. Author(s): Belshe RB, Burk B, Newman F, Cerruti RL, Sim IS. Source: The Journal of Infectious Diseases. 1989 March; 159(3): 430-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2915166
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Responses of the urinary excretion of homovanillic acid and of 5-hydroxy-indol-acetic acid to treatment with L-dopa and amantadine. Author(s): Molnar G, Fodor A. Source: Ther Hung. 1973; 21(1): 35-40. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4792890
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Reversible pathologic jealousy (Othello syndrome) associated with amantadine. Author(s): McNamara P, Durso R. Source: Journal of Geriatric Psychiatry and Neurology. 1991 July-September; 4(3): 157-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1953968
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Review of 38 cases of subacute sclerosing panencephalitis: effect of amantadine on the natural course of the disease. Author(s): Robertson WC Jr, Clark DB, Markesbery WR. Source: Annals of Neurology. 1980 October; 8(4): 422-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7436385
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Rimantadine hydrochloride and amantadine hydrochloride use in influenza A virus infections. Author(s): Tominack RL, Hayden FG. Source: Infectious Disease Clinics of North America. 1987 June; 1(2): 459-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3332798
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Role of amantadine in the management of neuroleptic-induced extrapyramidal syndromes: overview and pharmacology. Author(s): Allen RM. Source: Clinical Neuropharmacology. 1983; 6 Suppl 1: S64-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6196112
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Sarcoidosis in two patients with chronic hepatitis C treated with interferon, ribavirin and amantadine. Author(s): Perez-Alvarez R, Perez-Lopez R, Lombrana JL, Rodriguez M, Rodrigo L. Source: Journal of Viral Hepatitis. 2002 January; 9(1): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11851906
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Sensitivity of influenza A virus to amantadine. Author(s): Jackson GG. Source: The Journal of Infectious Diseases. 1977 August; 136(2): 301-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=894081
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Sequential outbreak of influenza A and B in a nursing home: efficacy of vaccine and amantadine. Author(s): Libow LS, Neufeld RR, Olson E, Breuer B, Starer P. Source: Journal of the American Geriatrics Society. 1996 October; 44(10): 1153-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8855992
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Sequential trial upon the awakening effect of amantadine after ketamine anaesthesia. Author(s): Domenichini E, Carbonera D, Pagnin A, Scherini A. Source: Curr Ther Res Clin Exp. 1972 November; 14(11): 707-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4629107
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Short-term effect of amantadine sulphate on motor performance and reaction time in patients with idiopathic Parkinson's disease. Author(s): Pinter MM, Birk M, Helscher RJ, Binder H. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1999; 106(7-8): 711-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10907729
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Small airways dysfunction in influenza A virus infection: therapeutic role and potential mode of action of amantadine. Author(s): Little JW, Hall WJ, Douglas RG Jr. Source: Annals of the New York Academy of Sciences. 1977 March 4; 284: 106-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=280133
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Spectroscopic characterization of vesicle formation on heated human erythrocytes and the influence of the antiviral agent amantadine. Author(s): Herrmann A, Lentzsch P, Lassmann G, Ladhoff AM, Donath E. Source: Biochimica Et Biophysica Acta. 1985 January 10; 812(1): 277-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2981546
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Status of amantadine in control of influenza. Author(s): Tilles JG. Source: The New England Journal of Medicine. 1971 November; 285(22): 1260-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4939800
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Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine. Author(s): Deep P, Dagher A, Sadikot A, Gjedde A, Cumming P. Source: Synapse (New York, N.Y.). 1999 December 15; 34(4): 313-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10529725
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Studies on induced influenza in man. I. Double-blind studies designed to assess prophylactic efficacy of amantadine hydrochloride against a2/Rockville/1/65 strain. Author(s): Togo Y, Hornick RB, Dawkins AT Jr. Source: Jama : the Journal of the American Medical Association. 1968 March 25; 203(13): 1089-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4868123
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Studies on induced influenza in man. II. Double-blind study designed to assess the prophylactic efficacy of an analogue of amantadine hydrochloride. Author(s): Dawkins AT Jr, Gallager LR, Togo Y, Hornick RB, Harris BA. Source: Jama : the Journal of the American Medical Association. 1968 March 25; 203(13): 1095-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4870515
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Subacute sclerosing panencephalitis. Elevated Epstein-Barr virus antibody titers and failure of amantadine therapy. Author(s): Joncas J, Geoffroy G, McLaughlin B, Albert G, Lapointe N, David P, Lafontaine R, Granger-Julien M. Source: Journal of the Neurological Sciences. 1974 April; 21(4): 381-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4362620
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Successful trial of amantadine hydrochloride for two patients with alternating hemiplegia of childhood. Author(s): Sone K, Oguni H, Katsumori H, Funatsuka M, Tanaka T, Osawa M. Source: Neuropediatrics. 2000 December; 31(6): 307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11508550
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Superficial punctate keratitis and corneal abrasion due to amantadine hydrochloride. Author(s): Nogaki H, Morimatsu M. Source: Journal of Neurology. 1993 June; 240(6): 388-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8336180
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Symmetrel in Parkinson' disease. Author(s): Getz R. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1970 August 22; 44(33): 955-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5453174
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The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. Author(s): Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 December; 303(3): 959-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438515
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The combination therapy of interferon and amantadine hydrochloride for patients with chronic hepatitis C. Author(s): Nakamura H, Uyama H, Enomoto H, Kishima Y, Yamamoto M, Yoshida K, Okuda Y, Hirotani T, Kuroda T, Ito H, Matsuda M, Terabayashi M, Noguchi S. Source: Hepatogastroenterology. 2003 January-February; 50(49): 222-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630027
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The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study. Author(s): Snow BJ, Macdonald L, Mcauley D, Wallis W. Source: Clinical Neuropharmacology. 2000 March-April; 23(2): 82-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10803797
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The effect of lactate on sex differences in rat renal tubular energy-dependent transport of the organic cation amantadine. Author(s): Bobby B, Sitar DS. Source: Pharmacology. 2001; 62(3): 188-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11287821
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The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Author(s): Pud D, Eisenberg E, Spitzer A, Adler R, Fried G, Yarnitsky D. Source: Pain. 1998 April; 75(2-3): 349-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9583771
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The N-methyl-D-aspartate receptor channel blocker amantadine does not cause histopathological alterations in human brain tissue. Author(s): Kornhuber J, Jellinger K, Wiltfang J, Leblhuber F, Riederer P. Source: Acta Neuropathologica. 1999 July; 98(1): 85-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10412804
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The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. Author(s): Griffin SD, Beales LP, Clarke DS, Worsfold O, Evans SD, Jaeger J, Harris MP, Rowlands DJ. Source: Febs Letters. 2003 January 30; 535(1-3): 34-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560074
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The roles of amantadine, rimantadine, ursodeoxycholic acid, and NSAIDs, alone or in combination with alpha interferons, in the treatment of chronic hepatitis C. Author(s): Younossi ZM, Perrillo RP. Source: Seminars in Liver Disease. 1999; 19 Suppl 1: 95-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10349697
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The visuo-cognitive and motor effect of amantadine in non-Caucasian patients with Parkinson's disease. A clinical and electrophysiological study. Author(s): Bandini F, Pierantozzi M, Bodis-Wollner I. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002; 109(1): 41-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793161
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Therapeutic efficacy of N-methyl D-aspartate antagonist amantadine in febrile catatonia. Author(s): Northoff G, Lins H, Boker H, Danos P, Bogerts B. Source: Journal of Clinical Psychopharmacology. 1999 October; 19(5): 484-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10505599
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Transient benefit of amantadine in Parkinson's disease: the facts about the myth. Author(s): Factor SA, Molho ES. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1999 May; 14(3): 515-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10348482
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Treatment of chronic hepatitis C patients with amantadine. Author(s): Yagura M, Harada H. Source: Journal of Gastroenterology. 2001 November; 36(11): 759-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757748
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Treatment of chronic hepatitis C with amantadine hydrochloride in patients who had not responded to previous treatment with interferon-alpha and/or ribavirin. Author(s): Di Martino V, Boudjema H, Delacour T, Cazier A, Caron C, Coutarel P, Dumouchel P, Cadranel JF. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 March 1; 32(5): 830-1. Epub 2001 February 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11229855
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Treatment of chronic hepatitis C with amantadine. Author(s): Goff JS, Reveille RM, Johnson J. Source: Digestive Diseases and Sciences. 2000 July; 45(7): 1389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961719
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Treatment of chronic hepatitis C with amantadine. Author(s): Hubert IF, Lunel F, Cadranel JF, Oberti F, Cales P. Source: The American Journal of Gastroenterology. 1999 August; 94(8): 2316-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10445578
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Treatment with amantadine potentiated motor learning in a patient with traumatic brain injury of 15 years' duration. Author(s): Shiller AD, Burke DT, Kim HJ, Calvanio R, Dechman KG, Santini C. Source: Brain Injury : [bi]. 1999 September; 13(9): 715-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10507453
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Triple antiviral re-therapy for chronic hepatitis C with interferon-alpha, ribavirin and amantadine in nonresponders to interferon-alpha and ribavirin. Author(s): Zilly M, Lingenauber C, Desch S, Vath T, Klinker H, Langmann P. Source: European Journal of Medical Research. 2002 April 30; 7(4): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010649
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Triple combination of interferon alpha-2b, ribavirin, and amantadine for treatment of chronic hepatitis C. Author(s): Younossi ZM, Mullen KD, Hodnick S, Barnes DS, Carey WD, McCullough AC, Easley K, Gramlich T, Liebermann BY. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5): 427-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702987
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Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial. Author(s): Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Herrmann E, Spengler U, Goeser T, Nasser S, Wursthorn K, Pape GR, Hopf U, Zeuzem S. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1359-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774015
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Unexpected amantadine intoxication in the death of a trauma patient. Author(s): Hartshorne NJ, Harruff RC, Logan BK. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1995 December; 16(4): 340-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8599344
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Urinary excretion of amantadine by the elderly. Author(s): Montanari C, Ferrari P, Bavazzano A. Source: European Journal of Clinical Pharmacology. 1975 June 13; 8(5): 349-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1233234
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Urinary monoamine metabolite excretion in disorders of movement. Effects of amantadine and levodopa. Author(s): Lenman JA, Turnbull MJ, Reid A, Fleming AM. Source: Journal of the Neurological Sciences. 1977 June; 32(2): 219-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=874521
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Use and withdrawal of amantadine chemoprophylaxis during epidemic influenza A. Author(s): Muldoon RL, Stanley ED, Jackson GG. Source: Am Rev Respir Dis. 1976 April; 113(4): 487-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1267254
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Use of amantadine for chronic fatigue syndrome. Author(s): Bowman MA, Kirk JK, Michielutte R, Preisser JS. Source: Archives of Internal Medicine. 1997 June 9; 157(11): 1264-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9183239
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Use of amantadine in an epidemic of 'Hong Kong' influenza type A2 in family practice. Author(s): Watson GI. Source: The Practitioner. 1970 September; 205(227): 351-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5484914
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Use of amantadine in influenza: a second report. Author(s): Rose HJ. Source: J R Coll Gen Pract. 1983 October; 33(255): 651-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6644670
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Use of amantadine in Parkinson's disease. Results of a double-blind trial. Author(s): Dallos V, Heathfield K, Stone P, Allen FA. Source: British Medical Journal. 1970 October 3; 4(726): 24-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4919119
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Use of amantadine in the therapy and prophylaxis of A2 influenza. Author(s): Couch RB. Source: Bulletin of the World Health Organization. 1969; 41(3): 695-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5309494
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Use of amantadine in the United States, 1977-1982. Author(s): Bailowitz A, Kaslow RA. Source: The Journal of Infectious Diseases. 1985 February; 151(2): 372-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3968454
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Use of Viregyt (amantadine hydrochloride) in the treatment of epidemic influenza. Author(s): Mate J, Simon M, Juvancz I. Source: Ther Hung. 1971; 19(3): 117-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4946391
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Using cue reactivity to screen medications for cocaine abuse: a test of amantadine hydrochloride. Author(s): Robbins SJ, Ehrman RN, Childress AR, O'Brien CP. Source: Addictive Behaviors. 1992 September-October; 17(5): 491-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1332435
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Visible diode laser induced fluorescence detection for capillary electrophoretic analysis of amantadine in human plasma following precolumn derivatization with Cy5.29.OSu. Author(s): Nagaraj S, Rahavendran SV, Karnes HT. Source: Journal of Pharmaceutical and Biomedical Analysis. 1998 November; 18(3): 41120. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10096835
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Vision loss associated with amantadine hydrochloride use. Author(s): Pearlman JT, Kadish AH, Ramseyer JC. Source: Jama : the Journal of the American Medical Association. 1977 March 21; 237(12): 1200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=576453
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Vision loss associated with amantadine hydrochloride. Author(s): Pearlman JT, Kadish AH, Ramseyer JC. Source: Archives of Neurology. 1977 March; 34(3): 199-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=843253
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Visual hallucinations and delirium during treatment with amantadine (Symmetrel). Author(s): Postma JU, Van Tilburg W. Source: Journal of the American Geriatrics Society. 1975 May; 23(5): 212-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=123540
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World health news. Influenza prophylaxis with amantadine. Author(s): Abramson JH. Source: Isr J Med Sci. 1972 January; 8(1): 84-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4554756
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Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home. Author(s): Lee C, Loeb M, Phillips A, Nesbitt J, Smith K, Fearon M, McArthur MA, Mazzulli T, Li Y, McGeer A. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2000 November; 21(11): 700-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11089653
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CHAPTER 2. NUTRITION AND AMANTADINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and amantadine.
Finding Nutrition Studies on Amantadine 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 “amantadine” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “amantadine” (or a synonym): •
A PET study with [11-C]raclopride in Parkinson's disease: preliminary results on the effect of amantadine on the dopaminergic system. Author(s): Department of Neurology, IRCCS San Raffaele, Milan, Italy. Source: Volonte, M A Moresco, R M Gobbo, C Messa, C Carpinelli, A Rizzo, G Comi, G Fazio, F Neurol-Sci. 2001 February; 22(1): 107-8 1590-1874
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A pilot trial of amantadine for ambulatory withdrawal for cocaine dependence. Author(s): Yale University, Department of Psychiatry, New Haven, Connecticut 06519. Source: Morgan, C Kosten, T Gawin, F Kleber, H NIDA-Res-Monogr. 1988; 8181-5 10469516
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Combined antiinfluenza activity of a plant preparation SHS-174 and amantadine derivatives. Author(s): Institute of Microbiology, Bulgarian Academy of Sciences, Sofia. Source: Serkedjieva, J Zgorniak Nowosielska, I Acta-Virol. 1993 August; 37(4): 258-64 0001-723X
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Gender-associated differences in rat renal tubular amantadine transport and absence of stereoselective transport inhibition by quinine and quinidine in distal tubules. Author(s): Department of Pharmacology, University of Manitoba, Winnipeg, Canada. Source: Wong, L T Escobar, M R Smyth, D D Sitar, D S J-Pharmacol-Exp-Ther. 1993 December; 267(3): 1440-4 0022-3565
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Inhibitory effects of the antiparkinsonian drugs memantine and amantadine on Nmethyl-D-aspartate-evoked acetylcholine release in the rabbit caudate nucleus in vitro. Author(s): Neuropharmakologisches Labor, Neurologischen Universitatsklinik, Freiburg, Federal Republic of Germany. Source: Lupp, A Lucking, C H Koch, R Jackisch, R Feuerstein, T J J-Pharmacol-Exp-Ther. 1992 November; 263(2): 717-24 0022-3565
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Investigation on possible antioxidative properties of the NMDA-receptor antagonists ketamine, memantine, and amantadine in comparison to nicanartine in vitro. Author(s): Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany. Source: Lupp, A Kerst, S Karge, E Quack, G Klinger, W Exp-Toxicol-Pathol. 1998 September; 50(4-6): 501-6 0940-2993
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Locomotor effects of amantadine in the mouse are not those of a typical glutamate antagonist. Author(s): Department of Pharmacology, School of Pharmacy, London, United Kingdom. Source: Starr, M S Starr, B S J-Neural-Transm-Park-Dis-Dement-Sect. 1995; 9(1): 31-43 0936-3076
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Site-selective effect of bicarbonate on amantadine renal transport: quinine-sensitive in proximal vs quinidine-sensitive sites in distal tubules. Author(s): Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada. Source: Escobar, M R Sitar, D S J-Pharmacol-Exp-Ther. 1995 April; 273(1): 72-9 0022-3565
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Stereoselective inhibition of amantadine accumulation by quinine and quinidine in rat renal proximal tubules and cortical slices. Author(s): Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada. Source: Wong, L T Smyth, D D Sitar, D S J-Pharmacol-Exp-Ther. 1990 October; 255(1): 271-5 0022-3565
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Successful protection by amantadine hydrochloride against lethal encephalitis caused by a highly neurovirulent recombinant influenza A virus in mice. Author(s): Department of Microbiology, Fukui Medical University School of Medicine, Fukui, Japan. Source: Mori, I Liu, B Hossain, M J Takakuwa, H Daikoku, T Nishiyama, Y Naiki, H Matsumoto, K Yokochi, T Kimura, Y Virology. 2002 November 25; 303(2): 287-96 00426822
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Synthesis of valproic acid amides of a melatonin derivative, a piracetam and amantadine for biological tests. Author(s): Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
[email protected] Source: Chatterjie, N Alexander, G Wang, H Neurochem-Res. 2001 October; 26(10): 11716 0364-3190
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The combined use of amantadine and l-dopa/carbidopa in the treatment of chronic brain injury. Author(s): Division of Geriatrics and Neuropsychiatry, Western Psychiatric Hospital and Clinic, Pittsburgh, PA 15213, USA. Source: Kraus, M F Maki, P Brain-Inj. 1997 June; 11(6): 455-60 0269-9052
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Twenty-five years of amantadine therapy in Parkinson's disease. Author(s): Neurological Department, Geriatric Centre “Wienerwald”, Vienna, Austria. Source: Danielczyk, W J-Neural-Transm-Suppl. 1995; 46399-405 0303-6995
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Use of digitalis glycosides to identify the mechanisms of amantadine transport by renal tubules. Author(s): Department of Pharmacology, University of Manitoba, Winnipeg, Canada. Source: Escobar, M R Sitar, D S J-Pharmacol-Exp-Ther. 1996 June; 277(3): 1189-94 00223565
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to amantadine; 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: •
Minerals Carnitine (L-Carnitine) Source: Integrative Medicine Communications; www.drkoop.com L-Carnitine Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND AMANTADINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to amantadine. 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 amantadine 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 “amantadine” (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 amantadine: •
A pilot trial of high-dose alpha-tocopherol and ascorbate in early Parkinson's disease. Author(s): Fahn S. Source: Annals of Neurology. 1992; 32 Suppl: S128-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1510371
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Activity of a monoclonal antibody-saporin-6 conjugate against B-lymphoma cells. Author(s): Bregni M, Lappi DA, Siena S, Formosa A, Villa S, Soria M, Bonadonna G, Gianni AM. Source: Journal of the National Cancer Institute. 1988 June 1; 80(7): 511-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3259267
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Advances in the Diagnosis and Management of Influenza. Author(s): Jefferson T.
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Source: Current Infectious Disease Reports. 2002 June; 4(3): 206-210. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015912 •
Affinity and specificity of N-methyl- D-aspartate channel blockers affect their ability to disrupt prepulse inhibition of acoustic startle in rats. Author(s): Wiley JL, Harvey SA, Balster RL, Nicholson KL. Source: Psychopharmacology. 2003 February; 165(4): 378-85. Epub 2002 November 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459931
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Attempts at stimulation of immune response in acute lymphod leukaemia. Author(s): Mathe G, Schwarzenberg L, Schneider M, Haya M, de Vassal F, Pouillart P, Amiel JL. Source: Proc R Soc Med. 1972 March; 65(3): 266-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5083315
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Can we treat respiratory failure in Friedreich ataxia? Author(s): Botez MI, Mayer P, Bellemare F, Couture J. Source: Archives of Neurology. 1997 August; 54(8): 1030-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9267979
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Cerebellar ataxia. Author(s): Perlman SL. Source: Current Treatment Options in Neurology. 2000 May; 2(3): 215-224. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096749
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Chemotherapy of influenza. Author(s): Esanu V. Source: Virologie. 1982 October-December; 33(4): 283-302. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6761956
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Clinical issues in current drug therapy for dementia. Author(s): Forstl H. Source: Alzheimer Disease and Associated Disorders. 2000; 14 Suppl 1: S103-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10850737
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Combined antiinfluenza virus activity of Flos verbasci infusion and amantadine derivatives. Author(s): Serkedjieva J. Source: Phytotherapy Research : Ptr. 2000 November; 14(7): 571-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11054856
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Comparative study of antiproliferative effects of chlorpromazine, 7,8dioxochlorpromazine, amantadine-N-mustard, rutin-N-mustard and alpha, beta and gamma interferon on K-562 cells in vitro. Author(s): Molnar J, Pragai B, Berencsi K, Mandi Y, Foldeak S. Source: Acta Microbiol Hung. 1985; 32(4): 379-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3939072
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Cortical reorganisation and chronic pain: implications for rehabilitation. Author(s): Flor H. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2003 May; (41 Suppl): 66-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12817660
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Current treatment for Alzheimer disease and future prospects. Author(s): Tariot PN, Federoff HJ. Source: Alzheimer Disease and Associated Disorders. 2003 July-September; 17 Suppl 4: S105-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512816
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Detection of the production of reactive oxygen species by neutrophils in whole blood: modulation by adamantanes and triggering by Fe(3+)-ions. Author(s): Schempp H, Albrecht-Goepfert E, Elstner EF. Source: Z Naturforsch [c]. 1999 July-August; 54(7-8): 562-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10488564
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Diagnosis and management of Alzheimer's disease. Author(s): Coll PP, Fortinsky RH, Kaplan R, Song C. Source: Conn Med. 2003 September; 67(8): 505-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587132
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Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons. Author(s): Swerdlow NR, Stephany N, Shoemaker JM, Ross L, Wasserman LC, Talledo J, Auerbach PP. Source: Psychopharmacology. 2002 October; 164(1): 82-92. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12373422
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Effects of inhibitors of the cytoplasmic structures and functions on the early phase of infection of cultured cells with simian virus 40. Author(s): Shimura H, Umeno Y, Kimura G. Source: Virology. 1987 May; 158(1): 34-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3033894
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Evaluation of antihuman T lymphocyte saporin immunotoxins potentially useful in human transplantation. Author(s): Siena S, Bregni M, Formosa A, Martineau D, Lappi DA, Bonadonna G, Gianni AM. Source: Transplantation. 1988 November; 46(5): 747-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3264092
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Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents. Author(s): Backhauss C, Krieglstein J. Source: European Journal of Pharmacology. 1992 May 14; 215(2-3): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1396990
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Huntington's disease: prospects for neuroprotective therapy 10 years after the discovery of the causative genetic mutation. Author(s): Hersch SM. Source: Current Opinion in Neurology. 2003 August; 16(4): 501-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869810
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Idiopathic spasmodic torticollis. Author(s): Jorgenson C, Porphyris H. Source: J Neurosurg Nurs. 1985 June; 17(3): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2409249
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In vivo anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase. Author(s): Nagai T, Miyaichi Y, Tomimori T, Suzuki Y, Yamada H. Source: Antiviral Research. 1992 September; 19(3): 207-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1444327
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Inhibition of binding of Clostridium difficile toxin by steroids. Author(s): Chang TW, Gorbach SL, Bartlett JG. Source: The Journal of Infectious Diseases. 1980 July; 142(1): 113. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6772711
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Inhibition of influenza virus infection by pine cone antitumor substances. Author(s): Nagata K, Sakagami H, Harada H, Nonoyama M, Ishihama A, Konno K. Source: Antiviral Research. 1990 January; 13(1): 11-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2334167
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Inhibition of malaria parasite invasion into erythrocytes pretreated with membraneactive drugs. Author(s): McColm AA, Hommel M, Trigg PI.
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Source: Molecular and Biochemical Parasitology. 1980 April; 1(2): 119-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6255328 •
Inhibitors of influenza virus replication. Author(s): Schild GC, Oxford JS. Source: British Medical Bulletin. 1979 January; 35(1): 87-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=367492
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Intermittent tremor-bursts induced by chlorpromazine and pentobarbitone in guinea pigs: a new tremor model. Author(s): Tan U, Gepdiremen A, Banoglu N, Kutlu N. Source: The International Journal of Neuroscience. 1991 December; 61(3-4): 221-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1824383
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Ketamine induction and amantadine. Author(s): Lucca GP, DeDonato A, Montanari C. Source: Br J Clin Pract. 1975 January; 29(1): 15-18. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1095044
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New experimental and clinical data on leukaemia immunotherapy. Author(s): Mathe G, Schwarzenberg L, Amiel JL, Pouillart P, Hayat M, de Vassal F, Rosenfeld C, Jasmin C. Source: Proc R Soc Med. 1975 April; 68(4): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1060146
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Non-cholinergic strategies for treating and preventing Alzheimer's disease. Author(s): Doraiswamy PM. Source: Cns Drugs. 2002; 16(12): 811-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12421115
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Observations on the psychopharmacology of the aged. Author(s): Eisdorfer C. Source: Journal of the American Geriatrics Society. 1975 February; 23(2): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=237957
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Preliminary result of a new protocol for the active immunotherapy of acute lymphoblastic leukaemia: inhibition of the immunotherapeutic effect by Vincristine or Adamantadine. Author(s): Mathe G, Amiel JL, Schwarzenberg L, Schneider M, Hayat M, de Vassal F, Jasmin C, Rosenfeld C, Pouillart P.
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Source: Rev Eur Etud Clin Biol. 1971 March; 16(3): 216-24. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4997294 •
Sildenafil in the treatment of female sexual dysfunction induced by selective serotonin reuptake inhibitors. Author(s): Shen WW, Urosevich Z, Clayton DO. Source: J Reprod Med. 1999 June; 44(6): 535-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10394548
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Synthesis and characterization of an antihuman T-lymphocyte saporin immunotoxin (OKT1-SAP) with in vivo stability into nonhuman primates. Author(s): Siena S, Lappi DA, Bregni M, Formosa A, Villa S, Soria M, Bonadonna G, Gianni AM. Source: Blood. 1988 August; 72(2): 756-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3042047
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Therapy of Morbus Parkinson and radical-induced neurotoxicity in the rat--in vivo voltammetric studies. Author(s): Wesemann W. Source: Journal of Neural Transmission. Supplementum. 1992; 38: 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1283403
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Towards a cross-species pharmacology of sensorimotor gating: effects of amantadine, bromocriptine, pergolide and ropinirole on prepulse inhibition of acoustic startle in rats. Author(s): Swerdlow NR, Taaid N, Oostwegel JL, Randolph E, Geyer MA. Source: Behavioural Pharmacology. 1998 September; 9(5-6): 389-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9832924
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Treatment of Alzheimer's disease: current status and new perspectives. Author(s): Scarpini E, Scheltens P, Feldman H. Source: Lancet. Neurology. 2003 September; 2(9): 539-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941576
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Treatment of chronic hepatitis C virus infection. Author(s): Malnick SD, Beergabel M, Lurie Y. Source: The Annals of Pharmacotherapy. 2000 October; 34(10): 1156-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11054985
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Treatment of post herpetic neuralgia in the elderly. Author(s): Robertson DR, George CF.
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Source: British Medical Bulletin. 1990 January; 46(1): 113-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2405937
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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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to amantadine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Flu Source: Integrative Medicine Communications; www.drkoop.com Influenza Source: Healthnotes, Inc.; www.healthnotes.com Influenza Source: Integrative Medicine Communications; www.drkoop.com
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Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Amantadine Source: Healthnotes, Inc.; www.healthnotes.com Antiviral Drugs Source: Healthnotes, Inc.; www.healthnotes.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. PATENTS ON AMANTADINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “amantadine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on amantadine, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Amantadine By performing a patent search focusing on amantadine, 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 8Adapted
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 amantadine: •
Amantadine hydrochloride syspension with enhanced dissolution characteristics for use in soft gelatin capsules Inventor(s): Torosian; George (Lynbrook, NJ) Assignee(s): Du Pont Merck Pharmaceutical Company (Wilmington, DE) Patent Number: 5,175,002 Date filed: October 2, 1991 Abstract: There are provided, novel no or low wax formulations for amantadine hydrochloride and methods for preparing such formulations. Excerpt(s): This invention relates to improved formulations for water soluble compounds such as amantadine hydrochloride, particularly, formulations for amantadine hydrochloride, which, absent or with reduction of high melting point waxes, have significantly enhanced dissolution rates. Amantadine hydrochloride is a well known compound commercially available as Symmetrel.RTM. from E. I. du Pont de Nemours and Company, Wilmington, Del. Available dosage forms of Symmetrel.RTM. are soft gelatin capsules and oral syrup. U.S. Pat. No. 3,310,469 assigned to Du Pont, describes compositions containing amantadine. Traditionally, when manufacturing oral pharmaceutical dosage forms such as soft gelatin capsules, for highly water soluble active ingredients, such as amantadine hydrochloride, the active ingredient is not dissolved but rather is suspended in a oleaginous mixture which is then used to fill the capsule. The suspensions used as fill material in the preparation of soft gelatin capsules must usually be sufficiently viscous to avoid the sedimentation of the suspended drug substance during the capsule filling. This process may take several hours. This fill variation is directly related to the dose variation from capsule to capsule and dependent upon the dynamic homogeneity of this suspension over the processing time. Web site: http://www.delphion.com/details?pn=US05175002__
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Antidepressant combination Inventor(s): Smith, Jr.; Dewey H. (Wilmington, DE), Vernier; Vernon G. (Newark, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,148,896 Date filed: February 22, 1978 Abstract: Amantadine and molindone or their pharmaceutically suitable salts, useful for treatment of depression. Excerpt(s): This invention relates to antidepressant combinations of amantadine and molindone, or their pharmaceutically suitable acid addition salts. Amantadine (1adamantanamine), particularly in its salt form as amantadine hydrochloride, is an antiviral agent effective against A.sub.2 (Asian) influenza in animals and man, and is effective for treatment of parkinsonism. Molindone (3-ethyl-6,7-dihydro-2-methyl-5(morpholinomethyl)indol-4(5H)-one), particularly in salt form as molindone hydrochloride, is known to have antipsychotic properties.
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Web site: http://www.delphion.com/details?pn=US04148896__ •
Antiviral activities of dansylcadaverine and closely related compounds Inventor(s): Pastan; Ira H. (Potomac, MD), Willingham; Mark C. (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 4,396,628 Date filed: February 26, 1982 Abstract: The entry of animal viruses into their host cells proceeds via a specialized internalization pathway involving clathrin coated regions of the plasma membrane. In the present invention, there has been examined the effect of dansylcadaverine compared with amantadine and other antiviral agents as to the entry of vesicular stomatitis virus (VSV) into mouse cells. It was found that both compounds inhibit VSV entry. Both compounds inhibit the uptake of.alpha.sub.2 macroglobulin (.alpha.2M), a protein that binds to specific membrane receptors and follows the same route of internalization. Dansylcadaverine is 20 fold more potent than amantadine to the blocking virus and also to the.alpha.sub.2 macroglobulin uptake. Excerpt(s): Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 6th edition, 1980, lists among antiviral agents in the chapter "Antiviral Agents" (pages 12401243) amantadine (1-adamantanamine) and ara-A, an analog of adenosine (arabinose is the 1'-epimer of ribose) tradename Vidarabine, and human interferon. Hoffmann, "Structure, Activity and Mode of Action of Amantadine HCl and Related Compounds," Antibiotics Chemother., Vol. 27, pp. 233-250 (Karger, Basel 1980). Pastan and Willingham, "Receptor-Mediated Endocytosis of Hormones in Cultured Cells", Ann. Rev. Physiol., 43:239-250, 1981. Web site: http://www.delphion.com/details?pn=US04396628__
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Expression of influenza a M2 protein in baculovirus Inventor(s): Black; Renee (Atlanta, GA), Kendal; Alan P. (Atlanta, GA), Rota; Paul A. (Decatur, GA) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,290,686 Date filed: July 31, 1991 Abstract: The present invention relates to baculovirus-expressed influenza antigens, in particular, to the influenza A membrane protein, M2, expressed from Autographa Californica nuclear polyhedrosis virus (AcNPV). The present invention further relates to a method to increase the yield of baculovirus-expressed M2 proteins in host cells by culturing the recombinant baculovirus infected host cells with an amantadine-like drug. Other aspect of the present invention relate to the use of baculovirus-expressed M2 proteins in reproducible and routine assays for the seradiagnosis of influenza A virus infections as an alternative to the more burdensome complement fixation and hemagglutination tests.
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Excerpt(s): The present invention relates to baculovirus-expressed influenza antigens, in particular, to the influenza A membrane protein, M2 expressed from Autographa Californica nuclear polyhedrosis virus (AcNPV). The invention further relates to immunoassays for the detection of influenza viral infections and to the use of such protein in vaccines against influenza A. The M2-protein of influenza A viruses is a membrane-spanning protein. It is found within membranes of virus-infected cells (R.A. Lamb and P.W. Choppin Virology 112:729-737 (1981); R.A. Lamb et al, Cell 40:627-633 (1985)). A small number of M2 proteins are also present in virus particles (S.L. Zebedee and R.A. Lamb J. Virol. 62:2762-2772 (1988)). Mutations occur in the transmembrane region of M2 protein present in viruses selected in vitro or in vivo to be resistant to the anti-viral agents amantadine and rimantadine (A.J. Hay et al, EMBO J. 4:3021-3024 (1985); W.J. Bean et al, J. Infect. Dis. 159:1050-1056 (1989)). One model for the function of M2 protein is that it possess ion-channel activity, which is inhibited by amantadine-like agents (R.J. Sugrue et al, EMBO J. 9:3469-3476, 1990; R.I. Sugrue et al, Virology 180:617624 (1991). Amantadine-like agents include amantadine and various N-alkyl derivatives of amantadine which inhibit neuromuscular transmission by interacting with the ion channel of the nicotinic acetylcholine receptor and competitively inhibit the binding of other channel blockers, phencyclidine and histrionicotoxin, to the receptor. Although under some circumstances amantadine may indirectly interfere with the correct processing of the cleaved hemagglutinin of the Rostock strain of Fowl Plague Virus (R.J. Sugrue et al, EMBO J. 9:3469-3476 (1990)), it is a general rule that amantadine-like agents inhibit an early event in the replication of influenza A viruses, which occurs prior to transcription and translation of the genome of infecting virions (Hay et al, (1985); A.J. Hay and M.C. Zambon, Multiple actions of amantadine against influenza viruses. In Becker Y. (ed) Antiviral drugs and interferon: the molecular basis of their activity. Martinus Niihoff Publishing, Boston MA, pp. 301-315, (1984)) including the Rostock virus. Hence, even the small number of M2 proteins within virus particles are presumably involved in the early event blocked by amantadine. However, direct evidence about the function of M2 protein or its interaction with amantadine is lacking. Since the M2 protein is conserved among various strains of influenza A virus, it may have potential for use as an influenza vaccine. It has recently been demonstrated that mice receiving passively transferred monoclonal antibody to M2 had lower liters of influenza virus in their lungs after intranasal challenge with live influenza virus (J. Treanor et al, J. Virol. 64:1375-1377 (1990)). Web site: http://www.delphion.com/details?pn=US05290686__ •
Synergistic combination of amantadiene and selegiline Inventor(s): Brade; Wolfgang (Wehrheim, DE), Hettche; Helmut (Offenbach, DE), Reischig; Dirk (Bad Homburg, DE) Assignee(s): Degussa Aktiengesellschaft (Frankfurt am Main, DE) Patent Number: 4,812,481 Date filed: April 15, 1987 Abstract: There are provided in medicaments with synergistic action containing a combination of amantadine and selegiline. Excerpt(s): Amantadine is a virustatic agent as well as an anti-Parkinsonism drug. The chemical designation is 1-amino-adamantane. Selegiline is an anti-depressant as well as an appetite depressant. The chemical designation is N-(1-phenyl-2-propyl)-N-methyl-2propinylamine. It has been discovered that the action of amantadine and its salts is
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surprisingly increased synergistically by combination with selegiline or salts of selegiline. Web site: http://www.delphion.com/details?pn=US04812481__ •
Use of amantadine for treatment of Hepatitis C Inventor(s): Smith; Jill P. (Camp Hill, PA) Assignee(s): The Penn State Research Foundation (University Park, PA) Patent Number: 5,849,800 Date filed: March 28, 1997 Abstract: Methods for treating patients with viral infection with pharmaceutical agents are disclosed. In one embodiment, the virus is Hepatitis C and the pharmaceutical agent is amantadine. The methods of the present invention can be used in patients that have not responded to or cannot tolerate interferon treatment, as well as patients under the age of eighteen. Excerpt(s): The present invention pertains to the treatment patients with viral disease utilizing pharmaceutical compositions. In particular, the present invention pertains to methods for the treatment of Hepatitis C viral infection in humans with amantadine. Seropositivity to hepatitis C occurs in approximately 0.4-2% of the U.S. population and accounts for the overwhelming majority of cases of hepatitis ›Stevens et al. JAMA 263:49-53, (1990)!. Recent knowledge of the gene structure of hepatitis C virus (HCV) has indicated that it is a single stranded RNA virus having a full length of about 9.5 kilobases ›Choo et al. Science, Vol 244, pp. 359-362 (1989)!. Because HCV is a virus very likely to mutate and is not well understood how it replicates, the development of vaccines or anti-HCV drugs is still very slow. Our understanding of the natural history of hepatitis C disease is evolving ›Alter et al. N Engl J Med 327:1899-1905, (1992)!. Studies have shown that hepatitis C infection is associated with the development of advanced liver disease ›Tong et al. N Engl J Med 332:1463-1466, (1995)! and hepatocellular carcinoma ›Liang et al. Hepatology 18:1326-1333, (1993) and Tsukuma et al. N Engl J Med 328:1797-1801, (1993)!, and liver failure due to hepatitis C infection is the most common indication for liver transplantation in many centers ›Ascher et al. Hepatology 20 ›suppl!:24-27, (1994)!. Web site: http://www.delphion.com/details?pn=US05849800__
Patent Applications on Amantadine As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to amantadine:
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This has been a common practice outside the United States prior to December 2000.
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IFN-alpha and amantadine for treating hepatitis C Inventor(s): Zahm, Friederike; (Freiburg, DE) Correspondence: Hoffmann-La Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20030031647 Date filed: September 6, 2002 Abstract: The present invention provides a method for treating chronic hepatitis C infections in patients in need of such treatment comprising administering an amount of IFN-.alpha. in association with an amount of amantadine effective to treat hepatitis C. In accordance with the invention, IFN-.alpha. and amantadine are administered at the same time or sequentially. The present invention also provides a kit for treating a hepatitis C infection containing IFN-.alpha. and amantadine in suitable dosage forms for administering the combination therapy. Excerpt(s): The present invention relates to the field of treatment of chronic hepatitis C infections using an amount of IFN-.alpha. in association with an amount of amantadine which amounts are effective to treat hepatitis C. Interferons (IFNs) are naturally occurring proteins which have antiviral, antiproliferative and immunoregulatory activity. Four distinct classes of interferons are known to exist in humans (Pestka et al. (1987) Ann. Rev. Biochem. 56, 727-777 and Emanual & Pestka (1993) J. Biol. Chem. 268, 12565-12569). The IFN-.alpha. family represents the predominant class of IFNs produced by stimulated peripheral blood leukocytes (Pestka et al., loc. cit.; Havell et al. (1975) Proc. Natl. Acad. Sd. USA 72, 2185-2187; Cavalieri et al. (1977) Proc. Natl. Acad. Sd. USA 74, 3287-3291), and lymphoblastoid and myeloblastoid cell lines (Familletti et al. (1981) Antimicrob. Agents. Chemother. 20, 5-9). The antiviral effect of IFN-.alpha. is achieved not by a direct influence on the viruses themselves, but by an activity on their target cells in the sense of a protection against the virus infection. The interferons can exert effects on cancer tumors and can influence the immune system of the body in that, for example, they activate macrophages and NK cells and intensify the expression of various immunologically significant constituents of the cell membrane. Details of the preparation of interferon-cDNA and the direct expression thereof, especially in E. coli, have been the subject of many publications. Thus, for example, the preparation of recombinant interferons is known, for example, from Nature 295 (1982), 503-508, Nature 284 (1980), 326-320, Nature 290 (1981), 20-26, Nucleic Acids Res. 8 (1980), 4057-4074, as well as from European Patents Nos. 32134, 43980 and 211148. IFN-.alpha. monotherapy is commonly used in the treatment of chronic hepatitis C infections, however this treatment is not always effective. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for assaying non-spermine/spermidine activity of spermidine/spermine N1acetyltransferase (SSAT) Inventor(s): Bras, Alvaro P.; (Winnipeg, CA), Sitar, Daniel S.; (Winnipeg, CA) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20020132280 Date filed: March 1, 2002
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Excerpt(s): This invention relates to a method for assaying activity of the enzyme spermidine/spermine N.sup.1-acetyltransferase (SSAT) using SSAT substrates by detecting acetylated forms of the SSAT substrates. SSAT substrates may include amantadine wherein metabolism of amantadine occurs in part by the action of the inducible enzyme SSAT to produce the acetylated metabolite N-acetylamantadine. Amantadine was first synthesized at the Du Pont laboratories in the 1960s (Davies et at., 1964) and has a unique polycyclic aliphatic structure, with an achiral primary amine that makes it a weak base (pKa=10.1). At physiological pH, it exists mainly in the cationic form. Amantadine has been used as an adjunct in the symptomatic relief of Parkinson's disease and for the prophylaxis and treatment of influenza A virus infection the two approved clinical indications for amantadine in Canada. The first report that addressed amantadine metabolism was by Bleidner et al. They stated that there was no evidence of acetylated or methylated forms of amantadine in human urine or other extraneous peaks that could be attributed to metabolites of the drug (Bleidner et al., 1965). This view was accepted and formed the basis of opinion concerning amantadine metabolism and the assumption that incomplete oral absorption could account for some of the unrecovered dose. More recently evidence indicates that amantadine is acetylated by a specific acetyltransferase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for preventing infectious respiratory diseases Inventor(s): Madhat, Maher N.; (Lexington, KY) Correspondence: Maher Madhat; 3305 Grasmere Drive; Lexington; KY; 40503; US Patent Application Number: 20030045577 Date filed: August 15, 2001 Abstract: A method and composition for treating patients with viral infection with pharmaceutical agents is disclosed. In one embodiment, the virus is influenza A and the pharmaceutical agent is rimantadine or amantadine. The methods of the present invention can be used as a way of eradicating influenza virus topically by direct administration of a dose--nasally--that is much lower than an oral therapeutic dose. Thereby avoiding the side effects associated with oral administration. Consequently, the low dose of the drug administered by this method will be well tolerated among age groups Excerpt(s): The present invention pertains to the prevention of viral disease in humans utilizing nasal pharmaceutical compositions. In particular, the present invention pertains to the method of the prevention of influenza A viral infection in humans with rimantadine or amantadine or their water soluble or insoluble salts thereof administered nasally. Epidemic influenza continues to be associated with significant morbidity in general population and mortality in the elderly and other risk patients. Although the case fatality rate averages less than 0.01%, tens of thousands of deaths occur each year. Amantadine is a drug developed in 1960s with diverse uses ranging from prevention of influenza A to the treatment of patients with Parkinson's disease [Aoki and Sitar, Clin Pharm 14:35-51, 1988]. Amantadine hydrochloride is a well known compound commercially available as Symmetral. Available dosage forms of Symmetrel.RTM. are soft gelatin capsules and oral syrup [U.S. Pat. No. 3,310,469 assigned to Du Pont describes composition-containing amantadine]. Elimination of amantadine is primarily through renal clearance by both glomerular filtration and tubular secretion. Amantadine accumulates in patients with renal dysfunction.
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Therefore, doses must be reduced in such patients to avoid toxicity [Aoki and Sitar, 1988]. Further, amantadine as an antiviral agent-of nucleic acid derivative type-is likely to bring about side effects such as deterioration of liver function, mutagenicity, subacute toxicity, teratogenicity and a decrease in reproductive efficiency [Virology-published by Raven press, pp 323-348, 1985]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Preparation of aqueous clear solution dosage forms with bile acids Inventor(s): Yoo, Seo Hong; (Wyckoff, NJ) Correspondence: Baker Botts L.L.P.; 44th Floor; 30 Rockefeller Plaza; New York; NY; 10112-4498; US Patent Application Number: 20020031558 Date filed: February 5, 2001 Abstract: Compositions for pharmaceutical and other uses comprising clear aqueous solutions of bile acids which do not form any detectable precipitates over selected ranges of pH values of the aqueous solution and methods of making such solutions. The compositions of the invention comprise water; a bile acid in the form of a bile acid, bile acid salt, or a bile acid conjugated with an amine by an amide linkage; and either or both an aqueous soluble starch conversion product and an aqueous soluble non-starch polysaccharide. The composition remains in solution without forming a precipitate over a range of pH values and, according to one embodiment, remains in solution for all pH values obtainable in an aqueous system. The composition, according to some embodiments, may further contain a pharmaceutical compound in a pharmaceutically effective amount. Non-limiting examples of pharmaceutical compounds include insulin, heparin, bismuth compounds, amantadine and rimantadine. Excerpt(s): This application claims the benefit of provisional application Ser. No. 60/180,268, filed Feb. 4, 2000 and is a continuation in part of application Ser. No. 09/357,549 filed Jul. 2, 1999 which claims the benefit of provisional application Ser. No. 60/094,069, filed Jul. 24, 1998, all of which are incorporated herein by reference. Bile acids salts which are organic acids derived from cholesterol are natural ionic detergents that play a pivotal role in the absorption, transport, and secretion of lipids. In bile acid chemistry, the steroid nucleus of a bile acid salt has the perhydrocyclopentano phenanthrene nucleus common to all perhydrosteroids. Distinguishing characteristics of bile acids include a saturated 19-carbon sterol nucleus, a beta-oriented hydrogen at position 5, a branched, saturated 5-carbon side chain terminating in a carboxylic acid, and an alpha-oriented hydroxyl group in the 3-position. The only substituent occurring in most natural bile acids is the hydroxyl group. In most mammals the hydroxyl groups are at the 3, 6, 7 or 12 positions. The common bile acids differ primarily in the number and orientation of hydroxyl groups on the sterol ring. The term, primary bile acid refers to these synthesized de novo by the liver. In humans, the primary bile acids include cholic acid (3.alpha., 7.alpha.12.alpha.-trihy- droxy-5.beta.-cholanic acid) ("CA") and chenodeoxycholic acid (3.alpha., 7.alpha.-dihydroxy-5.beta.-cholanic acid) ("CDCA"). Dehydroxylation of these bile acids by intestinal bacteria produces the more hydrophobic secondary bile acids, deoxycholic acid (3.alpha., 12.alpha.-dihydroxy-5.beta.-cholanic acid) ("DCA") and lithocholic acid (3.alpha.-hydroxy-5.beta.- -cholanic acid) ("LCA"). These four bile acids CA, CDCA, DCA, and LCA, generally constitute greater than 99 percent of the bile salt pool in humans. Secondary bile acids that have been metabolized by the liver are sometimes denoted as tertiary bile acids.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with amantadine, 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 “amantadine” (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 amantadine. You can also use this procedure to view pending patent applications concerning amantadine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. BOOKS ON AMANTADINE Overview This chapter provides bibliographic book references relating to amantadine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on amantadine include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Chapters on Amantadine In order to find chapters that specifically relate to amantadine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and amantadine 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 “amantadine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on amantadine: •
Alternative Therapies for Chronic Hepatitis C Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 159-186. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on alternative therapies for chronic hepatitis C is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 45 year old man with chronic hepatitis C and hyperlipidemia (excessive amounts of lipids in the blood) who was referred for antiviral treatment. Because of the patient's coronary artery disease, a decision was made to avoid ribavirin. In light of the low response rate to interferon
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monotherapy, adjunctive therapies were discussed, including the use of thymic peptides, aspirin like drugs, amantadine, and botanicals. The risks and benefits of iron reduction therapy were also discussed. After reviewing the alternatives, the patient opted to avoid all treatment until the availability of better antiviral options. The authors note that the need for alternative therapies for the treatment of hepatitis C is based on the realization that, despite major advanced in antiviral therapy, many patients fail to respond to the best agents currently available. Efficacy may be limited in some patients due to dose limiting toxicities, such as depression or anemia, or the presence of relative contraindications to therapy (cardiac disease, renal failure) that preclude the use of these agents. The role of aspirin like compounds seems to be limited to easing the side effects of interferon. 1 figure. 1 table. 67 references. •
Retreatment of Hepatitis C: Interferon Nonresponders Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 233-261. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on the retreatment of hepatitis C patients who have not responded to interferon (IFN) therapy is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 49 year old man who was diagnosed with subclinical chronic hepatitis C virus (HCV) infection. The patient received interferon therapy and tolerated it well, with minimal adverse effects. However, viral titer, after 3 months on interferon monotherapy, showed persistence of the HCV. He was considered a nonresponder and interferon therapy was discontinued. Additional treatments, including a longer course of interferons and a course of combination therapy with interferon and ribavirin, were undertaken. There was no substantial change in viral titer, although slight improvement in aminotransferase (ALT) levels was seen. The author discusses retreatment with alternative forms of interferon, and using adjunctive therapy, including iron reduction therapy, amantadine and rimantadine, ursodeoxychlic acid (UDCA), and nonsteroidal antiinflammatory drugs (NSAIDs). 4 tables. 92 references.
•
Topical and Systemic Antifungal and Antiviral Agents Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 6988. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:
[email protected]. Website: www.quintpub.com. PRICE: $32.00 plus shipping and handling. ISBN: 0867153970. Summary: This chapter on topical and systemic antifungal and antiviral agents is from a textbook that integrates basic facts and principles of antibiotic therapy with recentlyemerged concepts of care. The author notes that the last decade has seen an increase in the number of agents available for the treatment of fungi and viruses, in part due to research in treatments for people with HIV. The chapter covers only drugs already released or soon to be released by the FDA (Food and Drug Administration).
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Antifungals discussed are polyenes, including amphotericin B and nystatin; azoles, including ketoconazole, fluconazole, itraconazole, miconazole nitrate, clotrimazole, and topical azoles; allylamines and benzylamines; and miscellaneous antifungal drugs, including flucytosine, griseofulvin, potassium iodide, and topical agents. Antiviral agents discussed are nucleoside and nucleotide analogues, including acyclovir, valacyclovir hydrochloride, penciclovir, famciclovir, cidofovir, vidarabine, trifluridine, and idoxuridine, and ribavirin; pyrophosphate analogue, notably foscarnet sodium; carbon ring amines, including amantadine and rimantadine; neuraminidase inhibitors, including zanamivir and oseltamivir; recombinant protein; antisense oligonucleotide (fomivirsen); and a monoclonal antibody (palivizumab). For each drug, the author reviews indications, distribution in the body, adverse effects, the spectrum of efficacy, and drug variations (form and use). The chapter concludes with a review of the treatment of common oral fungal and viral infections. Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 2 figures. 5 tables. 17 references. •
Chapter 67: Movement Disorders Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 13 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides information on the symptoms, diagnosis, and treatment of various movement disorders, including tremors, cramps, myoclonus, hiccups, Tourette's syndrome, chorea, athetosis, Huntington's disease, dystonia, Parkinson's disease, progressive supranuclear palsy, Shy-Drager syndrome, and coordination disorders. Damage to or an abnormality of an area of the nervous system that regulates movement may cause a person to experience a movement disorder. A tremor is an involuntary, rhythmic, shaking movement that occurs when muscles repeatedly contract and relax. Types of tremors include action, resting, intention, essential, senile, and familial tremors. Although treatment is usually not needed for movement disorders, drugs may be helpful for some people. A cramp is a sudden, brief, usually painful contraction of a shortened muscle or group of muscles. Cramps are common in healthy people and do not need to be treated. Myoclonus causes a synchronous quick jerk of affected muscles. Antiseizure drugs may be used to treat severe cases of myoclonic jerks. Hiccups are repeated spasms of the diaphragm followed by quick, noisy closings of the glottis. They are caused when a stimulus triggers the nerves that contract the diaphragm. Most cures for hiccups require holding the breath to increase the amount of carbon dioxide in the blood. Stimulating the vagus nerve may also help. Tourette's syndrome is a hereditary disorder characterized by motor and vocal tics. Antipsychotic drugs may help suppress them. Chorea and athetosis are symptoms that can result from several different diseases, including Huntington's disease and Sydenham's disease. Drugs that block the action of dopamine may help control abnormal movements. Huntington's disease is an inherited disease characterized by abnormal movements and gradual loss of brain cells. There is no cure for Huntington's disease, but drugs may help relieve symptoms and control behavior. In people who have dystonia, muscles may freeze in the middle of an action. Dystonia seems to be caused by overactivity in several areas of the brain. Types of dystonia are idiopathic torsion dystonia, blepharospasm, torticollis, and spasmodic dysphonia. Treatment is limited. Drugs with anticholinergic properties may be helpful. Parkinson's
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disease is a progressive, degenerative disorder of the nervous system. Although the cause of nerve cell degeneration and dopamine loss is usually not known, Parkinson's disease is sometimes a very late complication of viral encephalitis or a complication of using certain drugs. Muscle stiffness develops in Parkinson's disease, and initiating a movement is difficult. Various drugs are used to treat this disease, including levodopa, bromocriptine, pergolide, selegiline, anticholinergics, antihistamines, antidepressants, propranolol, and amantadine. Progressive supranuclear palsy causes muscle rigidity, inability to roll the eyes upward, and weakness of the throat muscles. The cause is unknown, and there is no completely effective treatment. Shy-Drager syndrome causes malfunction and destruction of the autonomic nervous system. Treatment is the same as for Parkinson's disease but includes the drug fludrocortisone. Coordination disorders occur when the cerebellum is damaged.
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CHAPTER 6. PERIODICALS AND NEWS ON AMANTADINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover amantadine.
News Services and Press Releases One of the simplest ways of tracking press releases on amantadine 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 “amantadine” (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 amantadine. 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 “amantadine” (or synonyms). The following was recently listed in this archive for amantadine: •
Rimantadine may be safer than amantadine for influenza prophylaxis in elderly Source: Reuters Medical News Date: May 25, 2000
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “amantadine” (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 “amantadine” (or synonyms). If you know the name of a company that is relevant to amantadine, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “amantadine” (or synonyms).
Academic Periodicals covering Amantadine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to amantadine. In addition to
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these sources, you can search for articles covering amantadine 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 7. 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 amantadine. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with amantadine. 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 amantadine: Amantadine •
Systemic - U.S. Brands: Symmetrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202024.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. 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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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
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
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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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 Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “amantadine” (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 3904 18 996 18 22 4958
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “amantadine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on amantadine 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 amantadine. 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 amantadine. 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 “amantadine”:
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Influenza http://www.nlm.nih.gov/medlineplus/influenza.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Viral Infections http://www.nlm.nih.gov/medlineplus/viralinfections.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 amantadine. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Hepatitis C (HCV) Information Packet Contact: Hepatitis C Support Project, PO Box 427037, San Francisco, CA, 94142-7037, (415) 978-2400, http://www.hcvadvocate.org. Summary: This information packet, for the general public, provides information about the hepatitis C virus (HCV), which can cause chronic liver disease. It discusses the statistics of HCV incidents in the United States and it provides information on testing for HCV, its symptoms, treatment, and prevention. It discusses conditions linked to HCV, co-infection with HIV and HCV, and clinical trials. It presents treatment options from a western/conventional medicine and an alternative/complementary perspective. These treatments include interferon, rebetron, ribavirin, amantadine, infergen, pegylated (PEG), pegylated interferon, maxamine, ribozmes, new therapies, herbs, Traditional Chinese Medicine (TCM), acupuncture, and Qi Gong. The brochure provides information on managing HCV and discusses hepatitis A and B vaccines, nutrition, and additional self-care suggestions. For individuals interested in learning more about HCV, contact information for several organizations is provided. 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
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ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to amantadine. 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
•
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/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to amantadine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with amantadine. 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 amantadine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines.
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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 “amantadine” (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 “amantadine”. 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 “amantadine” (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 “amantadine” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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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/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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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/
•
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/
•
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
•
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/
•
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)
•
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/
•
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
•
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
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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AMANTADINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adamantane: A tricyclo bridged hydrocarbon. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] 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] Adjunctive Therapy: Another treatment used together with the primary treatment. Its
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purpose is to assist the primary treatment. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [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]
Dictionary 127
Alkaline: Having the reactions of an alkali. [EU] Alkalinization: The process by which a substance becomes an alkali. An alkali is the opposite of an acid. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [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] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence,
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found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
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] Antiallergic: Counteracting allergy or allergic conditions. [EU] Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac
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arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] 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] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the
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maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [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] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH]
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Aromatic-L-Amino-Acid Decarboxylases: An enzyme group with broad specificity. The enzymes decarboxylate a range of aromatic amino acids including dopa (dopa decarboxylase), tryptophan, and hydroxytryptophan. EC 4.1.1.28. [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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspartate: A synthetic amino acid. [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] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Athetosis: A derangement marked by ceaseless occurrence of slow, sinuous, writhing movements, especially severe in the hands, and performed involuntarily; it may occur after hemiplegia, and is then known as posthemiplegic chorea. Called also mobile spasm. [EU] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH]
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Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] 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] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benztropine: A centrally active muscarinic antagonist that has been used in the symptomatic treatment of Parkinson's disease. Benztropine also inhibits the uptake of dopamine. [NIH] Benzylamines: Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving
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chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biperiden: A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine. [NIH] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bladder: The organ that stores urine. [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] Blepharospasm: Excessive winking; tonic or clonic spasm of the orbicularis oculi muscle. [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 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] 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]
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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] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [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] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [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] 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] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the
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interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbidopa: A peripheral inhibitor of dopa decarboxylase. It is given in parkinsonism along with levodopa to inhibit the conversion of levodopa to dopamine in the periphery, thereby reducing the peripheral adverse effects, increasing the amount of levodopa that reaches the central nervous system, and reducing the dose needed. It has no antiparkinson actions when given alone. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac Glycosides: Substances obtained from species of Digitalis, Strophanthus, and other plants that contain specific steroid glycosides or their semisynthetic derivatives and used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the Na(+)-K(+)-exchanging ATPase and they are often used in cell biological studies for that purpose. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] 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
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negative pole during electrolysis. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [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 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 Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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]
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Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] 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] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] 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] Choleretic: A choleretic agent. [EU] 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] Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [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]
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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 Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [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] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] 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]
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Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cogwheel: Pushing on an arm causes it to move in jerky increments instead of smoothly. [NIH]
Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH]
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Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] 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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] 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] 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] 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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [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] Contralateral: Having to do with the opposite side of the body. [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]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU]
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Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] 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] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [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] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH]
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Cytomegalovirus Retinitis: Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. [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] Cytoplasmic Structures: Components of the cytoplasm excluding the cytosol. [NIH] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deja Vu: A subjective feeling that an experience which is occurring for the first time has been experienced before. [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] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dengue Virus: A species of the genus Flavivirus which causes an acute febrile and sometimes hemorrhagic disease in man. Dengue is mosquito-borne and four serotypes are known. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure.
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The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent. [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] 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] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [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] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Digitalis Glycosides: Glycosides from plants of the genus Digitalis. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all cardiac glycosides, but here is restricted to those related to Digitalis. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH]
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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] Dissection: Cutting up of an organism for study. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [NIH] Diuresis: Increased excretion of urine. [EU] 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] Dopa Decarboxylase: One of the aromatic-l-amino-acid decarboxylases, this enzyme is responsible for the conversion of dopa to dopamine. It is of clinical importance in the treatment of Parkinson's disease. EC 4.1.1.28. [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] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [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] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug 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] Duodenum: The first part of the small intestine. [NIH]
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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] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysphoria: Disquiet; restlessness; malaise. [EU] Dystonia: Disordered tonicity of muscle. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] 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] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] 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] Emetic: An agent that causes vomiting. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] 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.
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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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] 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] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a
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fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Febrile: Pertaining to or characterized by fever. [EU] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] 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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but
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distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent. [NIH] Fludrocortisone: A synthetic mineralocorticoid with anti-inflammatory activity. [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] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Foscarnet: An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes
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are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH]
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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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Griseofulvin: An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [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] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH]
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Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]
Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hemagglutinins: Agents that cause agglutination of red blood cells. They include antibodies, blood group antigens, lectins, autoimmune factors, bacterial, viral, or parasitic blood agglutinins, etc. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may
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persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [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] 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] 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] 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] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]
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Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] 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] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idoxuridine: An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent, particularly in the treatment of herpes simplex keratitis. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH]
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Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] 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] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infant, Newborn: An infant during the first month after birth. [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]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a
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step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Alfa-2a: A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-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] 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] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intravenous: IV. Into a vein. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for
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channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [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] Keratitis: Inflammation of the cornea. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between
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the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lentivirus Infections: Virus diseases caused by the Lentivirus genus. They are multi-organ diseases characterized by long incubation periods and persistent infection. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] 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] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [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]
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Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic. [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 Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Loc: A brain region associated with object recognition. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of
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plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maternal Exposure: Exposure of the female parent, human or animal, 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 that may affect offspring. It includes pre-conception maternal exposure. [NIH] Mazindol: Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into
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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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone,
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predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two 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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocular: Diplopia identified with one eye only; it may be induced with a double prism, or it may occur either as a result of double imagery due to an optical defect in the eye, or as a result of simultaneous use of normal and anomalous retinal correspondence. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [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] 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]
Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU]
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Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]
Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] 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] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] 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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU]
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Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]
Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] 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] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic
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cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [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]
Nitrite Reductases: A group of enzymes that oxidize diverse nitrogenous substances to yield nitrite. (Enzyme Nomenclature, 1992) EC 1. [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] Nitrogenase: An enzyme system that catalyzes the fixing of nitrogen in soil bacteria and blue-green algae (cyanobacteria). EC 1.18.6.1. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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 chromosomes. [NIH] Nystatin: Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex are nystatin A1, A2, and A3. [NIH] Oculi: Globe or ball of the eye. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH]
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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] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [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] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of
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increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]
Perineal: Pertaining to the perineum. [EU] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The
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peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Phallic: Pertaining to the phallus, or penis. [EU] 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] 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] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [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] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [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]
Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piracetam: A compound suggested to be both a nootropic and a neuroprotective agent. [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
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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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Pontine: A brain region involved in the detection and processing of taste. [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] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postoperative: After surgery. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] 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] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on
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the scope of the method and is determined by requirements such as sample throughout and costs. [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] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [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] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [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] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [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] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the
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nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] 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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH]
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Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary 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]
Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [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] 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
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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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor antagonist. [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] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]
Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [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] 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] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [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]
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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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
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] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic
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agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Rimantadine: An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] 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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH]
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Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
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Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
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] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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] Spectroscopic: The recognition of elements through their emission spectra. [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
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bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spermine: A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Stabilization: The creation of a stable state. [EU] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stereotypy: Unvarying repetition or unvarying persistence. [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] 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] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH]
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Striatum: A higher brain's domain thus called because of its stripes. [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] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supraspinal: Above the spinal column or any spine. [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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [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
Dictionary 179
meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] 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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Teratogenicity: The power to cause abnormal development. [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] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]
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Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Traction: The act of pulling. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of
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Parkinson disease. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trihexyphenidyl: A centrally acting muscarinic antagonist used in the treatment of parkinsonism and drug-induced extrapyramidal movement disorders and as an antispasmodic. [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] 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] Uncompetitive: A type of enzyme inhibition that arises when the inhibitor cannot combine with the free enzyme, but is capable of combining only with the substrate-enzyme complex. [NIH]
Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] 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] 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] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true
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origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [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] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia virus and varicella zoster virus. [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 Proteins: Proteins found in any species of virus. [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] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH] Void: To urinate, empty the bladder. [NIH] Volition: Voluntary activity without external compulsion. [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] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by
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discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [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 Abdominal, 125, 143, 166, 174 Abrasion, 66, 125 Acceptor, 22, 125, 157, 165 Acetaldehyde, 125, 144 Acetaminophen, 43, 125 Acetylcholine, 74, 88, 125, 137, 163, 164 Acoustic, 78, 82, 125 Acyclovir, 97, 125 Adamantane, 10, 20, 88, 125 Adaptability, 125, 136 Adaptation, 125, 137 Adenine, 125 Adenocarcinoma, 125, 152 Adenosine, 87, 125, 134 Adjunctive Therapy, 96, 125 Adrenergic, 5, 126, 129, 130, 144, 146, 167, 170, 171, 178 Adverse Effect, 4, 24, 37, 58, 96, 97, 126, 130, 135, 156, 173, 175 Aerobic, 126, 161 Aerosol, 126, 178 Afferent, 126, 169, 177 Affinity, 78, 126, 131, 176 Age Groups, 12, 91, 126 Aged, 80 and Over, 126 Agglutinins, 126, 151 Agonist, 5, 11, 14, 25, 126, 130, 132, 134, 144, 162, 163, 166, 167 Airways, 65, 126 Akathisia, 39, 126, 130 Alanine, 25, 126 Aldehyde Dehydrogenase, 126, 144 Alertness, 126, 134 Algorithms, 126, 133 Alkaline, 127, 134 Alkalinization, 26, 127 Alkaloid, 127, 134, 138, 161, 163, 171, 173 Allylamine, 127 Alpha-1, 127, 141 Alternative medicine, 100, 127 Ameliorating, 18, 127 Amenorrhea, 127, 134 Amine, 91, 92, 127, 152 Amino Acid Sequence, 15, 127, 129, 149 Amino Acids, 12, 27, 127, 131, 147, 149, 155, 165, 166, 168, 170, 174, 180 Ammonia, 22, 127, 150
Amphetamine, 10, 38, 42, 127, 143, 159 Amplification, 13, 127 Amygdala, 10, 128, 132, 157, 179 Anaesthesia, 65, 128, 154 Anal, 128, 148 Analgesic, 125, 128, 134, 157, 161, 165, 172 Analog, 87, 125, 128, 148, 153 Analogous, 10, 128, 180 Anaphylatoxins, 128, 139 Anatomical, 128, 137, 154, 160, 174 Anemia, 96, 128, 158 Anesthesia, 45, 52, 128, 156, 169 Anesthetics, 26, 128, 146 Angina, 128, 164, 170 Angina Pectoris, 128, 170 Animal model, 13, 14, 21, 128 Anions, 128, 156 Annealing, 128, 168 Antagonism, 65, 128, 134 Antiallergic, 128, 169 Anti-Arrhythmia Agents, 128, 143 Antibacterial, 129, 177 Antibiotic, 96, 128, 129, 150, 164, 166, 177, 182 Antibodies, 15, 37, 126, 129, 151, 168 Antibody, 15, 37, 66, 77, 88, 97, 126, 129, 139, 152, 154, 159, 161, 176 Anticholinergic, 63, 97, 129 Anticoagulant, 129, 170, 183 Anticonvulsant, 129, 182 Antidepressant, 86, 129, 134, 148 Antiemetic, 129, 130, 137 Antifungal, 96, 129, 148, 150, 156, 160, 164 Antigen, 126, 129, 139, 152, 154, 159, 160 Antigen-Antibody Complex, 129, 139 Antihypertensive, 129, 166, 173 Anti-infective, 129, 134, 152 Anti-inflammatory, 125, 129, 131, 148 Anti-Inflammatory Agents, 129, 131 Antimetabolite, 125, 129, 174 Antimicrobial, 37, 39, 40, 49, 61, 62, 96, 129, 143 Antimycotic, 129, 138 Antineoplastic, 129, 155, 182 Antioxidant, 130, 165 Antiproliferative, 79, 90, 130 Antipruritic, 130, 134
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Antipsychotic, 86, 97, 130, 137, 163, 172, 173 Antipyretic, 125, 130, 172 Antispasmodic, 130, 165, 181 Antiviral Agents, 17, 87, 96, 130 Anus, 128, 130, 139, 155 Anxiety, 126, 130, 156, 166, 170 Apathy, 19, 130, 163 Apomorphine, 42, 43, 50, 130 Apoptosis, 8, 21, 25, 130, 135 Aqueous, 92, 130, 132, 142, 145, 152 Arginine, 18, 128, 130, 164, 171 Aromatic-L-Amino-Acid Decarboxylases, 131, 144 Arterial, 127, 131, 153, 164, 170 Arteries, 131, 133, 140, 162 Arterioles, 131, 133, 134 Artery, 95, 131, 133, 145, 159, 171, 182 Aspartate, 7, 19, 67, 68, 74, 78, 131, 156, 167 Aspergillosis, 131, 156 Aspirin, 62, 96, 131 Astrocytes, 131, 160, 161 Asymptomatic, 131, 152 Ataxia, 32, 78, 131, 136, 179 Athetosis, 97, 131 Atrial, 131, 183 Atrial Fibrillation, 131, 183 Atypical, 11, 131 Auditory, 131, 159, 169, 182 Autoimmune disease, 131, 162 Autonomic Nervous System, 98, 131, 167, 176, 178 Avian, 26, 132 Axons, 132, 143, 177 B Babesiosis, 132, 172 Baclofen, 8, 14, 132 Bacteria, 26, 92, 129, 132, 141, 145, 150, 160, 164, 168, 172, 177, 180, 181 Bacterial Infections, 132, 150, 173 Bactericidal, 132, 147 Basal Ganglia, 130, 131, 132, 137, 153, 157 Basal Ganglia Diseases, 131, 132, 137, 153 Base, 91, 125, 132, 141, 142, 149, 156, 179 Behavioral Symptoms, 11, 132 Benztropine, 37, 132 Benzylamines, 97, 132 Bile, 92, 132, 137, 143, 158, 177, 179, 181 Bile Acids, 92, 132, 177, 179 Bile Acids and Salts, 132 Binding Sites, 16, 132
Biochemical, 49, 81, 129, 132, 133, 156, 175 Biological response modifier, 133, 155 Biological Transport, 133, 143 Biopsy, 4, 133 Biosynthesis, 133, 138 Biotechnology, 27, 28, 100, 109, 133 Biperiden, 34, 43, 58, 133 Bismuth, 92, 133 Bladder, 133, 140, 162, 170, 174, 181, 183 Blastomycosis, 133, 156 Blepharospasm, 97, 133 Blood Platelets, 133, 175 Blood pressure, 129, 133, 137, 153, 161, 176 Blood vessel, 133, 135, 137, 145, 146, 149, 156, 176, 178, 179, 182 Blood-Brain Barrier, 133, 157 Body Fluids, 133, 176 Bone Marrow, 133, 149, 153, 158 Bradykinin, 134, 164 Brain Stem, 134, 136 Bromocriptine, 10, 14, 33, 34, 40, 45, 79, 82, 98, 134 Buccal, 134, 177 Bupivacaine, 134, 157 Buprenorphine, 39, 134 Bupropion, 14, 34, 134 Butyric Acid, 12, 134 C Caffeine, 11, 134 Calcium, 129, 134, 139 Camphor, 10, 134 Candidiasis, 134, 148 Capillary, 39, 71, 134, 135, 174, 182 Capillary Fragility, 135, 174 Capsules, 86, 91, 135, 144 Carbidopa, 48, 53, 75, 135 Carbohydrate, 135, 150, 168 Carbon Dioxide, 97, 135, 141, 148, 173 Carcinogenic, 135, 155, 165, 177 Carcinoma, 135 Cardiac, 96, 127, 128, 131, 134, 135, 138, 143, 146, 147, 157, 171, 177 Cardiac Glycosides, 135, 143 Cardioselective, 135, 170 Cardiotonic, 135, 143 Cardiovascular, 54, 127, 135, 175, 176 Carnitine, 38, 76, 135 Case report, 45, 135, 138 Case series, 32, 34, 135, 138 Caspase, 8, 135 Catecholamine, 135, 144, 167 Cations, 135, 156
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Cauda Equina, 136, 174 Caudate Nucleus, 74, 132, 136, 162 Cell Cycle, 136, 182 Cell Death, 21, 25, 130, 136, 162 Cell Division, 132, 136, 159, 161, 167, 169 Cell membrane, 90, 133, 136, 138, 143, 159, 176 Cell Physiology, 23, 136 Cell Respiration, 136, 161, 173 Cell Survival, 25, 136 Cerebellar, 32, 34, 78, 131, 136, 173, 180 Cerebellar Diseases, 131, 136, 180 Cerebellum, 98, 136, 173 Cerebral, 20, 131, 132, 133, 134, 136, 140, 142, 146, 147, 148, 151, 159, 171, 179 Cerebral Cortex, 131, 136, 147, 171 Cerebrospinal, 31, 59, 136 Cerebrospinal fluid, 31, 59, 136 Cerebrum, 136 Cervical, 13, 136, 151, 180 Cervix, 136, 137 Character, 128, 137, 142 Chemoreceptor, 130, 137 Chemotactic Factors, 137, 139 Chenodeoxycholic Acid, 92, 137, 181 Chin, 137, 160 Chlorpheniramine, 40, 137 Chlorpromazine, 79, 81, 137 Choleretic, 137, 143, 158, 181 Cholesterol, 92, 132, 137, 177 Cholic Acid, 92, 137 Cholinergic, 81, 130, 137, 164 Chorea, 35, 53, 54, 97, 130, 131, 137 Choreatic Disorders, 137 Chromatin, 130, 137, 158, 163 Chromosomal, 127, 137, 168 Chromosome, 138, 149, 157 Chronic Disease, 138, 157 Chronic Fatigue Syndrome, 70, 83, 138 Cidofovir, 97, 138 Cinchona, 138, 171 Clamp, 26, 138 Clathrin, 87, 138 Clinical study, 11, 138, 140 Clinical trial, 4, 8, 11, 12, 15, 17, 19, 20, 21, 35, 109, 114, 138, 140, 144, 170, 172 Clonic, 133, 138 Cloning, 133, 138 Clotrimazole, 97, 138 Coagulation, 133, 134, 138, 151, 179, 183 Coated Vesicles, 138 Coca, 138
Cocaine, 5, 8, 9, 12, 14, 15, 30, 33, 37, 39, 40, 56, 59, 71, 74, 138, 159 Cofactor, 139, 170, 179 Cognition, 11, 20, 139, 163 Cogwheel, 54, 139 Colloidal, 20, 139, 178 Colon, 13, 139 Combination Therapy, 67, 90, 96, 139 Combinatorial, 8, 139 Complement, 15, 87, 128, 139 Complementary and alternative medicine, 77, 84, 139 Complementary medicine, 77, 139 Complete response, 25, 139 Compliance, 9, 140 Computational Biology, 109, 140 Conception, 140, 159 Concomitant, 4, 34, 140 Conduction, 26, 129, 140 Confusion, 140, 144, 153, 163, 181 Congenita, 140, 172 Congestion, 130, 140 Conjugated, 92, 132, 137, 140, 141, 143, 150, 158 Conjunctiva, 140, 154 Connective Tissue, 133, 140, 147, 148, 158, 179 Consciousness, 6, 128, 140, 142, 171 Constipation, 130, 140 Constriction, 140, 156 Consultation, 8, 140 Contraindications, ii, 96, 140 Contralateral, 23, 140, 173 Controlled clinical trial, 20, 140 Controlled study, 11, 24, 36, 40, 52, 53, 58, 67, 140 Convulsions, 129, 140, 153, 163 Coordination, 15, 21, 97, 136, 140, 162 Cornea, 140, 156, 184 Coronary, 95, 128, 140, 162, 164 Cortex, 11, 141, 146, 169, 173 Cortical, 32, 75, 79, 141, 147, 163, 169, 175, 179 Cranial, 136, 141, 151, 163, 164, 167, 182 Crystallization, 26, 141 Cues, 12, 17, 141 Cultured cells, 20, 79, 141 Curative, 141, 163, 179 Cyanobacteria, 141, 164 Cyclic, 134, 141, 150, 164 Cyclodextrins, 20, 141 Cysteine, 7, 18, 27, 141
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Amantadine
Cystine, 141 Cytochrome, 9, 141, 173 Cytochrome b, 141, 173 Cytomegalovirus, 141, 142, 148 Cytomegalovirus Retinitis, 142, 148 Cytoplasm, 22, 130, 136, 142, 146, 158, 163, 174 Cytoplasmic Structures, 79, 142 Cytosine, 142, 148 Cytoskeletal Proteins, 138, 142 D Data Collection, 21, 142 De novo, 92, 142 Degenerative, 21, 98, 142, 151, 161 Deja Vu, 50, 142 Deletion, 13, 130, 142 Delirium, 71, 130, 142 Dementia, 12, 13, 20, 31, 78, 130, 142, 143 Denaturation, 14, 142, 168 Dendrites, 142, 143, 163 Dendritic, 14, 142 Dengue Virus, 28, 49, 142 Dentate Gyrus, 142, 152 Deoxycholic Acid, 92, 143 Depolarization, 8, 26, 143 Detergents, 92, 143 Detoxification, 10, 16, 33, 143 Deuterium, 10, 16, 143, 152 Dextroamphetamine, 127, 143, 160 Diagnostic procedure, 85, 100, 143 Diaphragm, 97, 143 Diffuse Axonal Injury, 19, 32, 143 Diffusion, 19, 133, 143, 154 Digestion, 21, 132, 143, 158, 177 Digitalis, 75, 135, 143 Digitalis Glycosides, 75, 143 Dihydroxy, 92, 143, 174 Dilator, 143, 164 Direct, iii, 7, 10, 27, 88, 90, 91, 103, 143, 144, 167, 172, 173, 178 Disease Progression, 13, 143 Disinfectant, 144, 147 Disorientation, 140, 142, 144 Disposition, 35, 144 Dissection, 15, 144 Distal, 74, 144, 167, 170 Disulfiram, 16, 144 Diuresis, 134, 144 Dopa, 33, 41, 42, 48, 50, 53, 54, 63, 65, 75, 131, 135, 144, 157 Dopa Decarboxylase, 65, 131, 135, 144 Dopamine Agonists, 12, 144
Dosage Forms, 86, 90, 91, 92, 144 Double-blind, 5, 6, 24, 25, 29, 30, 32, 36, 38, 40, 43, 45, 51, 52, 55, 58, 62, 65, 66, 67, 70, 144 Drug Interactions, 13, 104, 144 Drug Tolerance, 144, 179 Duodenum, 132, 144, 177 Dyes, 52, 145, 163 Dyskinesia, 30, 40, 56, 58, 59, 130, 145 Dysphonia, 97, 145 Dysphoria, 5, 145 Dystonia, 97, 130, 145 E Effector, 125, 139, 145 Efficacy, 5, 7, 8, 11, 14, 17, 19, 21, 24, 25, 28, 36, 43, 46, 52, 61, 64, 65, 66, 68, 96, 97, 145, 180 Electrolyte, 142, 145, 161, 168, 176 Electrons, 130, 132, 145, 156, 165, 172 Elementary Particles, 145, 170 Emboli, 145, 183 Embolism, 145, 171, 183 Embolization, 145, 183 Embryo, 45, 145, 154 Emetic, 130, 145 Emulsion, 145, 148 Encephalitis, 31, 75, 98, 145 Encephalitis, Viral, 145 Encephalopathy, 57, 146 Endemic, 146, 158 Endogenous, 144, 146, 147, 163 Endorphins, 146, 163 Endothelium, 146, 164 Endothelium-derived, 146, 164 Endotoxins, 139, 146 Enkephalins, 146, 163 Entorhinal Cortex, 146, 152 Environmental Health, 108, 110, 146 Enzymatic, 9, 134, 139, 146, 152, 168, 173 Epidemic, 58, 70, 91, 146 Epidemiological, 44, 146 Epinephrine, 126, 144, 146, 163, 164, 181 Epithelial, 125, 133, 146, 152, 161 Epithelial Cells, 146, 152, 161 Epithelium, 26, 27, 146, 184 Ergot, 134, 146 Erythrocytes, 65, 80, 128, 132, 133, 147, 172 Ethanol, 50, 147 Eukaryotic Cells, 142, 147, 154, 165 Evoke, 147, 177 Excitability, 129, 147, 171 Excitation, 137, 147, 163
189
Excitatory, 12, 132, 147, 150, 163 Excitatory Amino Acids, 12, 147, 163 Excitotoxicity, 21, 147 Excrete, 147, 173 Exhaustion, 128, 147, 158 Extracellular, 26, 131, 140, 147, 176 Extrapyramidal, 37, 41, 64, 126, 127, 130, 133, 144, 147, 181 F Family Planning, 109, 147 Family Practice, 49, 70, 147 Fat, 132, 133, 134, 137, 145, 147, 157, 162 Fatigue, 31, 38, 45, 60, 138, 147, 166 Febrile, 68, 142, 147, 159 Fibrosis, 44, 127, 147, 174 Filtration, 91, 147 Fissure, 142, 147, 169 Fixation, 87, 147 Flatus, 148 Fluconazole, 97, 148 Flucytosine, 97, 148 Fludrocortisone, 98, 148 Fluorescence, 14, 22, 71, 148 Fluoxetine, 39, 51, 148 Flushing, 144, 148 Fold, 14, 87, 147, 148 Foscarnet, 97, 148 Fossa, 136, 148 Fovea, 148 Frontal Lobe, 19, 41, 148, 169 G Ganglia, 125, 132, 148, 162, 167, 177, 178 Gas, 39, 46, 47, 127, 135, 143, 148, 152, 164, 173, 178 Gas exchange, 148, 173 Gastric, 13, 135, 144, 148, 152 Gastrin, 148, 152 Gastrointestinal, 134, 146, 147, 148, 159, 175, 176, 178 Gastrointestinal tract, 147, 148, 175 Gene, 13, 20, 25, 28, 89, 133, 148, 149 Gene Amplification, 13, 149 Gene Expression, 25, 149 Gene Therapy, 21, 149 Genetic Code, 149, 164 Genetic testing, 149, 168 Genetics, 15, 149 Genotype, 149, 167 Germ Cells, 149, 159, 165 Gland, 149, 153, 158, 166, 170, 175, 177 Glomerular, 91, 149, 173 Glomeruli, 149
Glomerulonephritis, 4, 149 Glomerulus, 149 Glottis, 97, 149 Glucans, 141, 149 Glucose, 141, 149, 150, 151, 153, 155, 174, 181 Glucuronic Acid, 150, 151 Glutamate, 8, 14, 74, 147, 150 Glutamic Acid, 150, 163 Glutamine, 18, 150 Glycerol, 134, 150 Glycine, 132, 137, 143, 150, 158, 163 Glycoproteins, 150, 155, 163, 176 Glycosidic, 150, 163, 165 Gonadal, 150, 177 Governing Board, 150, 169 Graft, 4, 150, 153 Graft Rejection, 150, 153 Graft Survival, 4, 150 Granulomatous Disease, Chronic, 150, 173 Griseofulvin, 97, 150 Guanylate Cyclase, 150, 164 H Habituation, 10, 47, 150 Half-Life, 6, 20, 150 Hallucinogen, 151, 167 Haloperidol, 35, 62, 151 Hay Fever, 137, 151 Headache, 134, 151, 153, 154 Hemagglutinins, 26, 151 Hemiparesis, 151 Hemiplegia, 66, 131, 151 Hemoglobin, 128, 147, 151 Hemoglobinopathies, 149, 151 Hemorrhage, 142, 151, 178 Hemostasis, 151, 175 Heparin, 92, 151 Hepatic, 25, 142, 151 Hepatitis C, 3, 30, 89, 95, 96, 114, 151 Hepatocellular, 89, 152 Hepatocellular carcinoma, 89, 152 Hepatocytes, 151, 152 Hereditary, 97, 137, 152, 161 Heredity, 148, 149, 152 Herpes, 62, 125, 152, 153, 182 Herpes virus, 152, 182 Herpes Zoster, 152 Hippocampus, 10, 142, 152, 157, 178 Histamine, 128, 130, 137, 152, 169 Histidine, 27, 43, 152, 155 Homeostasis, 26, 152, 176 Homologous, 141, 149, 152, 178
190
Amantadine
Hormone, 45, 146, 148, 152, 155, 159, 169 Hydrogen, 16, 92, 125, 127, 132, 135, 142, 143, 152, 153, 157, 161, 165, 170 Hydrogen Peroxide, 152, 157 Hydrolysis, 152, 163, 168, 170 Hydrophilic, 143, 152 Hydrophobic, 9, 92, 143, 152 Hydroxylation, 9, 153 Hyperlipidemia, 95, 153 Hypertension, 151, 153, 170 Hyperthyroidism, 153, 170 Hypoglycaemia, 142, 153 Hypokinesia, 153, 166 Hypotension, 8, 130, 140, 144, 153 Hypothalamus, 131, 153, 157 Hypoxia, 142, 153, 179 Hypoxic, 7, 18, 153 I Idiopathic, 21, 42, 65, 80, 97, 133, 153 Idoxuridine, 97, 153 Imidazole, 138, 152, 153, 160 Immune response, 39, 78, 129, 131, 150, 153, 178, 181, 183 Immune system, 4, 90, 153, 162, 181, 183 Immunity, 126, 153 Immunization, 153 Immunocompromised, 36, 61, 153 Immunogenic, 21, 153 Immunosuppressive, 4, 153 Immunosuppressive therapy, 153 Immunotherapy, 81, 153 Immunotoxin, 82, 154 Impairment, 12, 57, 131, 142, 145, 154, 160, 171 In situ, 14, 154 In Situ Hybridization, 14, 154 In vitro, 7, 20, 24, 27, 42, 45, 48, 74, 79, 88, 149, 154, 168 In vivo, 7, 20, 24, 80, 82, 88, 149, 151, 154 Incubation, 154, 156, 157 Incubation period, 154, 156, 157 Induction, 35, 42, 49, 50, 59, 81, 130, 154, 156, 169 Induction therapy, 50, 59, 154 Infant, Newborn, 126, 154 Infertility, 134, 154 Infiltration, 149, 154, 169, 184 Inflammation, 95, 96, 129, 131, 145, 147, 151, 152, 154, 156, 160, 168, 174, 177 Infusion, 31, 78, 154, 160, 180 Ingestion, 43, 45, 154, 168 Inhalation, 126, 154, 168
Initiation, 5, 154 Inotropic, 144, 155 Inpatients, 56, 155 Insight, 7, 155 Insulator, 155, 162 Insulin, 45, 92, 155 Insulin-dependent diabetes mellitus, 155 Interferon Alfa-2a, 36, 155 Interferon-alpha, 20, 29, 30, 35, 36, 51, 59, 60, 62, 68, 69, 155 Interleukin-2, 42, 155 Intermittent, 51, 81, 155, 158 Interstitial, 155, 159, 173 Intervertebral, 155, 172, 174 Intervertebral Disk Displacement, 155, 172, 174 Intestinal, 92, 137, 143, 155 Intestines, 125, 148, 155 Intoxication, 17, 69, 142, 155, 182, 183 Intracellular, 8, 15, 134, 138, 154, 155, 159, 164, 168, 172, 183 Intracellular Membranes, 155, 159 Intravenous, 52, 154, 155, 160 Involuntary, 58, 97, 132, 137, 155, 162, 176 Ion Channels, 26, 131, 155, 179 Ionizing, 156, 159 Ions, 79, 132, 145, 152, 156, 176 Ipsilateral, 23, 156, 173 Ischemia, 20, 128, 156, 163 Itraconazole, 97, 156 J Jealousy, 64, 156 K Kava, 80, 156 Kb, 108, 156 Keratitis, 66, 153, 156 Ketamine, 65, 74, 81, 156, 167 Ketoconazole, 97, 156 Kidney Transplantation, 3, 156 Kinetic, 18, 156 L Labile, 139, 156 Larynx, 149, 156, 182, 183 Latent, 10, 156 Laxative, 137, 156 Lectin, 156, 159 Lentivirus, 13, 156, 157 Lentivirus Infections, 13, 157 Lesion, 19, 133, 157, 158, 175, 179 Lethal, 75, 132, 157 Leucocyte, 127, 157 Leukaemia, 78, 81, 157
191
Leukemia, 149, 157 Levo, 144, 157 Levodopa, 34, 46, 47, 54, 55, 56, 58, 67, 69, 98, 135, 144, 157, 175 Lidocaine, 52, 157 Life cycle, 22, 157 Ligaments, 140, 157 Ligands, 16, 22, 157 Limbic, 10, 128, 157, 169 Limbic System, 128, 157, 169 Linkage, 92, 157 Lipid, 8, 50, 150, 155, 157, 162, 165 Lipid Peroxidation, 8, 157, 165 Lithium, 54, 130, 158 Lithocholic Acid, 92, 158 Liver, 3, 51, 55, 67, 89, 92, 95, 96, 114, 125, 132, 135, 137, 141, 145, 150, 151, 152, 158 Liver Transplantation, 89, 158 Lobe, 19, 158 Loc, 90, 158 Localization, 15, 29, 158 Localized, 148, 151, 154, 158, 167, 181 Long-Term Care, 48, 158 Loop, 29, 158 Lymph, 136, 146, 158 Lymph node, 136, 158 Lymphatic, 146, 154, 158 Lymphoblastic, 81, 158 Lymphocytes, 129, 153, 155, 157, 158, 183 Lymphoid, 129, 157, 158 Lymphoma, 77, 158 Lysine, 155, 158 Lytic, 158, 183 M Malaise, 145, 158 Malaria, 80, 138, 158, 159 Malaria, Falciparum, 158, 159 Malaria, Vivax, 158, 159 Malignant, 57, 62, 63, 125, 130, 159 Manic, 130, 158, 159, 171 Manifest, 151, 159 Maternal Exposure, 54, 159 Mazindol, 14, 159 Meatus, 159, 182 Mediate, 20, 144, 159 Mediator, 144, 155, 159, 175 MEDLINE, 109, 159 Meiosis, 159, 178, 179 Memantine, 5, 7, 12, 17, 18, 20, 48, 74, 159 Membrane Fusion, 26, 159 Membrane Proteins, 16, 23, 159 Memory, 9, 11, 42, 43, 142, 159
Meninges, 136, 160, 177 Meningitis, 148, 156, 160 Menopause, 160, 170 Mental, iv, 4, 7, 43, 56, 108, 110, 136, 137, 139, 140, 142, 144, 147, 153, 159, 160, 170, 171, 174, 181 Mental Disorders, 153, 160, 170, 171 Mental Health, iv, 4, 108, 110, 160, 171 Mental Retardation, 7, 160 Mesolimbic, 130, 160 Metabolite, 14, 69, 91, 160 Metastasis, 160 Metastatic, 21, 160 Metastatic cancer, 21, 160 Methylphenidate, 25, 160 Micelle, 48, 160 Miconazole, 97, 160 Microbe, 160, 180 Microbiology, 15, 39, 46, 49, 52, 53, 74, 75, 125, 131, 160 Microglia, 131, 160, 161 Microorganism, 139, 160, 166, 183 Mineralocorticoid, 148, 160 Mitochondria, 29, 161, 165 Mitosis, 130, 161 Modeling, 13, 161 Modification, 21, 49, 161, 171 Modulator, 17, 161 Molecular, 7, 13, 15, 18, 26, 48, 81, 88, 109, 111, 133, 140, 142, 151, 161, 169, 172, 178, 180 Molecule, 16, 26, 129, 132, 139, 145, 146, 147, 149, 150, 151, 152, 156, 161, 165, 168, 172 Monitor, 13, 161, 164 Monoamine, 48, 69, 127, 143, 161, 175 Monoclonal, 37, 77, 88, 97, 161 Monocular, 23, 161 Mononuclear, 48, 161 Monotherapy, 29, 90, 96, 161 Mood Disorders, 19, 161 Morphine, 43, 130, 134, 161, 162, 165 Motility, 161, 175 Motion Sickness, 161, 162, 169 Motor nerve, 161, 164, 167 Movement Disorders, 21, 33, 52, 58, 68, 97, 114, 127, 130, 161, 179, 181 Mucosa, 161, 169, 177 Multiple sclerosis, 31, 35, 38, 42, 45, 162 Mutagenicity, 92, 162 Mutate, 89, 162 Myalgia, 154, 162
192
Amantadine
Myelin, 162 Myocardial infarction, 162, 170, 183 Myoclonus, 32, 97, 162 Myotonia, 162, 172 N Naloxone, 162 Naltrexone, 16, 162 Narcolepsy, 143, 160, 162 Narcotic, 125, 161, 162 Nasal Mucosa, 154, 162 Nausea, 129, 130, 144, 162, 181 Necrosis, 130, 142, 162 Neostriatum, 136, 162 Nervous System, 13, 18, 37, 40, 97, 125, 126, 127, 131, 134, 135, 136, 138, 143, 148, 150, 151, 157, 159, 160, 161, 162, 163, 166, 175, 178, 179, 182 Neural, 10, 24, 52, 59, 65, 68, 74, 75, 82, 126, 160, 162, 176 Neuralgia, 82, 163, 168 Neuraminidase, 24, 57, 97, 163 Neurobehavioral Manifestations, 143, 163 Neuroblastoma, 14, 163 Neuroleptic, 37, 41, 56, 57, 59, 62, 63, 64, 126, 130, 163 Neurologic, 13, 163 Neuromuscular, 88, 125, 163 Neuromuscular Junction, 125, 163 Neuronal, 8, 18, 163 Neurons, 12, 26, 48, 138, 142, 143, 147, 148, 157, 163, 164, 177, 178 Neuropathy, 163, 167, 174 Neurophysiology, 31, 41, 143, 163 Neuroprotective Agents, 20, 21, 163 Neurotoxicity, 7, 34, 82, 163 Neurotransmitter, 12, 21, 125, 134, 144, 147, 150, 152, 156, 163, 164, 178, 179 Neutrophils, 26, 79, 163, 173 Niacin, 163, 181 Nicotine, 10, 163 Nitric Oxide, 7, 18, 164 Nitrite Reductases, 22, 164 Nitrogen, 127, 141, 148, 150, 164, 181 Nitrogenase, 22, 164 Nitroglycerin, 7, 18, 164 Nonverbal Communication, 164, 171 Norepinephrine, 126, 144, 163, 164, 167, 173 Nuclear, 10, 22, 87, 88, 132, 145, 147, 157, 162, 164, 179 Nuclei, 14, 128, 145, 149, 157, 161, 164, 170
Nucleic acid, 20, 92, 142, 149, 154, 164, 174, 177, 183 Nystatin, 97, 164 O Oculi, 133, 164 Oculomotor, 19, 164 Ointments, 144, 165 Oligosaccharides, 163, 165 Oncogenic, 156, 165 Oocytes, 18, 165 Open Reading Frames, 156, 165 Ophthalmology, 148, 165 Opiate, 14, 161, 162, 165 Opium, 161, 165 Orbicularis, 133, 165 Organ Transplantation, 3, 165 Organelles, 138, 142, 165 Orthostatic, 130, 165 Outpatient, 5, 8, 22, 63, 165 Overdose, 45, 165 Ovum, 157, 165, 169 Oxidation, 22, 125, 130, 141, 157, 165 Oxidative Stress, 21, 165 P Palate, 165, 177 Palliative, 59, 165, 179 Palsy, 97, 165 Pancreas, 125, 155, 166 Pancreatic, 135, 166 Panic, 33, 166 Parasite, 80, 166 Parasitic, 151, 166 Paresis, 151, 166 Parkinsonism, 21, 41, 46, 50, 53, 54, 55, 58, 63, 86, 88, 130, 133, 135, 157, 166, 181 Partial response, 25, 166 Particle, 160, 166, 176, 183 Patch, 26, 166 Pathogen, 7, 154, 166 Pathologic, 23, 64, 130, 133, 140, 166, 177, 182 Pathologic Processes, 130, 166 Patient Education, 114, 118, 120, 123, 166 Pemoline, 35, 45, 166 Penicillin, 128, 166 Peptide, 23, 166, 168, 170 Pergolide, 82, 98, 166 Perineal, 166, 172 Perioperative, 43, 166 Peripheral blood, 48, 90, 155, 166 Peripheral Nervous System, 133, 146, 151, 163, 165, 166, 167, 178
193
Peripheral Nervous System Diseases, 151, 167 Peripheral Neuropathy, 29, 167 Phallic, 148, 167 Pharmaceutical Solutions, 144, 167 Pharmacokinetic, 6, 38, 167 Pharmacologic, 8, 10, 19, 128, 150, 167, 180 Pharmacotherapy, 14, 16, 38, 57, 59, 82, 167 Pharynx, 154, 167, 182 Phencyclidine, 88, 167 Phenotype, 13, 167 Phenyl, 88, 167 Phenylpropanolamine, 50, 62, 167 Physiologic, 126, 133, 144, 150, 153, 162, 167, 172, 180 Pilot Projects, 15, 167 Pilot study, 16, 19, 29, 30, 35, 47, 51, 59, 60, 167 Piracetam, 75, 167 Plants, 127, 135, 138, 143, 150, 156, 164, 167, 174, 180, 182 Plasma, 20, 34, 39, 41, 46, 47, 52, 71, 87, 126, 129, 136, 151, 161, 168 Plasma cells, 129, 168 Plasmid, 149, 168 Platelet Aggregation, 128, 164, 168 Platelets, 164, 168 Pneumonia, 37, 45, 140, 168 Poisoning, 38, 130, 142, 146, 155, 162, 168 Polymerase, 61, 130, 168 Polymerase Chain Reaction, 61, 168 Polymorphism, 39, 168 Polypeptide, 127, 168, 169, 170, 184 Polysaccharide, 92, 129, 168 Pontine, 10, 168 Posterior, 128, 131, 136, 165, 166, 168, 174 Postherpetic Neuralgia, 127, 168 Postoperative, 43, 168 Post-synaptic, 19, 168 Post-traumatic, 161, 168 Potassium, 97, 161, 168, 171 Practicability, 168, 180 Practice Guidelines, 110, 169 Precursor, 144, 145, 146, 157, 164, 169, 177, 181 Prefrontal Cortex, 10, 169 Presynaptic, 19, 163, 169, 179 Private Sector, 19, 169 Probe, 10, 14, 169 Problem Solving, 9, 169 Procaine, 157, 169
Progesterone, 169, 177 Progression, 4, 21, 128, 169, 175 Progressive, 4, 21, 97, 142, 144, 162, 169, 173 Projection, 164, 169, 173 Prolactin, 134, 169 Promethazine, 43, 137, 169 Prone, 5, 169 Prophase, 165, 169, 178 Prophylaxis, 24, 37, 43, 44, 58, 70, 71, 91, 99, 130, 170, 174, 181, 183 Propranolol, 5, 16, 98, 170 Prostate, 170, 172, 174 Prostatectomy, 170, 172 Protease, 139, 170 Protein C, 17, 127, 138, 170 Protein Conformation, 127, 170 Protein S, 17, 130, 133, 149, 170, 174 Proteolytic, 127, 139, 170 Protocol, 81, 170 Protons, 26, 152, 156, 170, 172 Protozoan, 158, 170 Proximal, 66, 74, 75, 144, 169, 170 Pruritus, 169, 170 Psychiatric, 9, 12, 17, 19, 38, 75, 160, 170 Psychic, 160, 171, 175 Psychoactive, 171, 183 Psychopharmacology, 30, 32, 39, 40, 43, 68, 78, 79, 81, 171 Psychosis, 130, 171 Psychotherapy, 6, 37, 171 Psychotomimetic, 127, 143, 171 Psychotropic, 32, 171 Public Health, 17, 110, 171 Public Policy, 109, 171 Publishing, 27, 88, 96, 171 Pulmonary, 133, 171, 182, 183 Pulmonary Embolism, 171, 183 Pulse, 10, 161, 171 Putrescine, 171, 177 Pyramidal Tracts, 147, 171 Q Quality of Life, 20, 171 Quinidine, 47, 74, 75, 138, 171 Quinine, 47, 74, 75, 138, 171 R Race, 144, 172 Racemic, 144, 172 Raclopride, 74, 172 Radiation, 128, 145, 148, 156, 159, 172, 183 Radical prostatectomy, 43, 172 Radiculopathy, 172, 174
194
Amantadine
Radioactive, 150, 152, 164, 165, 172 Randomized, 5, 6, 11, 12, 14, 16, 19, 24, 25, 29, 30, 32, 35, 45, 47, 48, 51, 52, 53, 62, 67, 145, 172 Reaction Time, 53, 65, 172 Reactive Oxygen Species, 8, 79, 172 Receptor, 7, 14, 17, 18, 20, 34, 65, 67, 74, 87, 88, 125, 129, 137, 144, 172, 175 Receptors, Serotonin, 172, 175 Recombinant, 15, 26, 75, 87, 90, 97, 155, 172 Recombination, 149, 172 Recovery of Function, 25, 172 Rectum, 130, 139, 148, 170, 172 Red blood cells, 33, 147, 151, 172, 174 Red Nucleus, 131, 173 Refer, 1, 134, 139, 146, 148, 152, 158, 163, 171, 173, 180 Refraction, 173, 176 Refractory, 40, 173 Regimen, 5, 145, 167, 173, 174 Relapse, 6, 8, 9, 35, 47, 63, 173 Reliability, 6, 14, 173 Renal failure, 96, 142, 173 Renal tubular, 67, 74, 173 Reserpine, 133, 173 Respiration, 135, 137, 161, 173 Respiratory Burst, 26, 173 Respiratory failure, 78, 173 Response rate, 95, 173 Retinal, 142, 161, 173 Retreatment, 96, 173 Retropubic, 170, 172, 174 Retropubic prostatectomy, 172, 174 Retroviral vector, 149, 174 Rhinitis, 137, 151, 174, 175 Ribavirin, 4, 27, 29, 35, 36, 42, 45, 47, 50, 51, 59, 62, 64, 68, 69, 95, 96, 97, 114, 174 Ribose, 87, 125, 174 Ribosome, 174, 180 Rigidity, 45, 54, 98, 166, 167, 174 Risk patient, 44, 91, 174 Rod, 138, 174 Rutin, 79, 174 S Saponins, 174, 177 Schizoid, 174, 183 Schizophrenia, 34, 44, 63, 174, 183 Schizotypal Personality Disorder, 174, 183 Sciatica, 52, 62, 174 Sclerosis, 162, 174 Screening, 11, 14, 16, 17, 30, 138, 175
Secretion, 91, 92, 134, 152, 155, 160, 161, 175 Sedative, 156, 169, 175 Sediment, 175 Sedimentation, 86, 175 Seizures, 142, 175 Selegiline, 88, 98, 175 Semisynthetic, 134, 135, 175 Senile, 97, 175 Sensibility, 128, 175 Sequela, 143, 175 Sequencing, 168, 175 Serotonin, 82, 130, 148, 163, 167, 172, 173, 175, 181 Serotypes, 142, 175 Serum, 6, 42, 45, 128, 139, 161, 175 Shock, 162, 175, 180 Side effect, 8, 19, 24, 25, 28, 39, 40, 56, 61, 91, 92, 96, 103, 126, 130, 159, 175, 180 Signs and Symptoms, 173, 175 Skeletal, 138, 171, 175, 176 Small intestine, 137, 144, 152, 155, 176 Smoking Cessation, 134, 176 Smooth muscle, 127, 128, 134, 152, 161, 164, 176, 178 Social Environment, 171, 176 Sodium, 97, 129, 161, 171, 172, 176, 182 Sodium Channels, 172, 176, 182 Solitary Nucleus, 131, 176 Solvent, 16, 147, 150, 167, 176 Somatic, 157, 159, 161, 167, 169, 176, 182 Sound wave, 140, 176 Spasm, 130, 131, 133, 176 Spasmodic, 80, 97, 176 Spasticity, 7, 132, 176 Specialist, 115, 176 Specificity, 14, 25, 78, 126, 131, 176 Spectroscopic, 22, 65, 176 Spectrum, 56, 97, 138, 156, 160, 176, 182 Spermidine, 90, 91, 177 Spermine, 90, 91, 177 Spinal cord, 131, 132, 134, 136, 137, 151, 160, 162, 163, 166, 167, 171, 172, 177, 178 Spinal Cord Diseases, 151, 177 Spinal Nerve Roots, 172, 174, 177 Stabilization, 16, 177 Steady state, 20, 177 Steel, 138, 177, 182 Stereotypy, 43, 177 Steroid, 92, 132, 135, 174, 177 Stimulant, 127, 134, 143, 152, 160, 166, 177 Stimulus, 17, 97, 147, 155, 172, 177
195
Stomach, 125, 148, 152, 155, 162, 167, 176, 177 Stomatitis, 87, 177 Stool, 139, 177 Strand, 14, 168, 177 Stress, 131, 135, 148, 162, 165, 177, 181 Striatum, 10, 65, 162, 178 Stroke, 7, 11, 20, 23, 108, 163, 178 Subacute, 64, 66, 154, 178 Subclinical, 96, 154, 175, 178 Subiculum, 152, 178 Subspecies, 176, 178, 182 Substance P, 160, 175, 178 Substrate, 9, 163, 178, 181 Suction, 147, 178 Superoxide, 173, 178 Supraspinal, 132, 178 Suspensions, 86, 178 Sympathetic Nervous System, 131, 178 Sympathomimetic, 127, 143, 144, 146, 164, 167, 178 Symptomatic, 36, 91, 127, 132, 178 Symptomatic treatment, 127, 132, 178 Synapse, 65, 126, 163, 169, 178, 179, 180 Synapsis, 178 Synaptic, 14, 19, 163, 164, 178, 179 Synaptic Transmission, 164, 179 Synergistic, 88, 169, 179 Systemic, 8, 20, 25, 39, 96, 104, 133, 134, 142, 144, 146, 154, 177, 179, 181, 183 T Tardive, 56, 58, 59, 130, 179 Taurine, 8, 132, 137, 143, 158, 179 Temporal, 128, 152, 159, 179 Temporal Lobe, 128, 179 Tendon, 176, 179 Teratogenicity, 92, 179 Thalamic, 131, 179 Thalamic Diseases, 131, 179 Thalamus, 157, 169, 179 Therapeutics, 20, 29, 47, 63, 66, 74, 75, 87, 104, 179 Thermal, 168, 179 Thoracic, 143, 179 Thrombin, 168, 170, 179 Thrombomodulin, 170, 179 Thrombosis, 162, 170, 178, 179 Tolerance, 39, 125, 134, 179 Tone, 176, 180 Tonic, 133, 135, 180 Tonicity, 145, 180 Topical, 96, 147, 152, 180
Torsion, 97, 180 Torticollis, 80, 97, 180 Toxic, iv, 21, 135, 138, 143, 153, 154, 159, 163, 171, 180 Toxicity, 27, 37, 92, 144, 180 Toxicology, 6, 9, 14, 34, 46, 74, 110, 180 Toxin, 21, 80, 179, 180 Traction, 138, 180 Transfection, 20, 133, 149, 180 Transfusion, 151, 180 Translation, 88, 180 Transmitter, 125, 131, 144, 147, 156, 159, 164, 180 Transplantation, 3, 80, 153, 180 Trauma, 11, 20, 32, 69, 132, 142, 151, 162, 163, 172, 179, 180 Treatment Outcome, 9, 11, 16, 180 Tremor, 81, 97, 166, 180 Trigger zone, 130, 181 Trihexyphenidyl, 42, 181 Tryptophan, 22, 131, 175, 181 Tyrosine, 144, 181 U Uncompetitive, 18, 20, 181 Unconscious, 128, 181 Uremia, 173, 181 Urethra, 170, 181 Urinary, 5, 47, 63, 69, 170, 174, 181 Urinate, 181, 183 Urine, 6, 9, 12, 14, 15, 38, 46, 48, 91, 133, 144, 181 Urine Testing, 15, 181 Ursodeoxycholic Acid, 67, 181 Urticaria, 137, 181 Uterus, 136, 137, 169, 181 V Vaccination, 24, 60, 181 Vaccine, 7, 13, 24, 49, 60, 64, 88, 170, 181, 182 Vaccinia, 181, 182 Vaccinia Virus, 181, 182 Vagus Nerve, 97, 176, 182 Valproic Acid, 75, 182 Vanadium, 22, 182 Varicella, 182 Vascular, 127, 146, 154, 164, 177, 181, 182 Vasodilation, 144, 182 Vasodilator, 134, 144, 152, 182 Vegetative, 43, 143, 182 Vein, 155, 164, 182 Venous, 164, 170, 182, 183 Venous Thrombosis, 182, 183
196
Amantadine
Venter, 182 Ventral, 10, 153, 164, 177, 182 Ventricle, 128, 136, 152, 153, 171, 179, 182 Venules, 133, 134, 182 Vesicular, 87, 152, 182 Veterinary Medicine, 109, 182 Vidarabine, 87, 97, 182 Viral Hepatitis, 35, 47, 50, 51, 62, 64, 95, 96, 183 Viral Proteins, 15, 183 Virulence, 15, 180, 183 Virulent, 15, 183 Virus Diseases, 130, 183 Virus Replication, 7, 81, 183 Visceral, 131, 157, 182, 183 Visceral Afferents, 131, 182, 183 Vitro, 45, 151, 183
Vivo, 20, 183 Vocal cord, 149, 183 Void, 20, 183 Volition, 155, 183 W Wakefulness, 142, 183 Warfarin, 10, 183 White blood cell, 129, 158, 168, 183 Withdrawal, 5, 40, 55, 57, 70, 74, 142, 183 X Xenograft, 128, 183 X-ray, 24, 26, 148, 164, 183 Y Yeasts, 167, 183 Z Zoster, 182, 183 Zymogen, 170, 184
