DIAZEPAM 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 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Diazepam: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83887-9 1. Diazepam-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 diazepam. 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 DIAZEPAM ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Diazepam ...................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. NUTRITION AND DIAZEPAM....................................................................................... 73 Overview...................................................................................................................................... 73 Finding Nutrition Studies on Diazepam ..................................................................................... 73 Federal Resources on Nutrition ................................................................................................... 77 Additional Web Resources ........................................................................................................... 77 CHAPTER 3. ALTERNATIVE MEDICINE AND DIAZEPAM ................................................................ 79 Overview...................................................................................................................................... 79 National Center for Complementary and Alternative Medicine.................................................. 79 Additional Web Resources ........................................................................................................... 93 General References ....................................................................................................................... 96 CHAPTER 4. DISSERTATIONS ON DIAZEPAM .................................................................................. 97 Overview...................................................................................................................................... 97 Dissertations on Diazepam .......................................................................................................... 97 Keeping Current .......................................................................................................................... 98 CHAPTER 5. PATENTS ON DIAZEPAM ............................................................................................. 99 Overview...................................................................................................................................... 99 Patents on Diazepam ................................................................................................................... 99 Patent Applications on Diazepam.............................................................................................. 118 Keeping Current ........................................................................................................................ 120 CHAPTER 6. BOOKS ON DIAZEPAM ............................................................................................... 121 Overview.................................................................................................................................... 121 Book Summaries: Online Booksellers......................................................................................... 121 The National Library of Medicine Book Index ........................................................................... 122 Chapters on Diazepam ............................................................................................................... 123 CHAPTER 7. MULTIMEDIA ON DIAZEPAM .................................................................................... 127 Overview.................................................................................................................................... 127 Bibliography: Multimedia on Diazepam .................................................................................... 127 CHAPTER 8. PERIODICALS AND NEWS ON DIAZEPAM ................................................................. 129 Overview.................................................................................................................................... 129 News Services and Press Releases.............................................................................................. 129 Academic Periodicals covering Diazepam.................................................................................. 131 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 133 Overview.................................................................................................................................... 133 U.S. Pharmacopeia..................................................................................................................... 133 Commercial Databases ............................................................................................................... 134 Researching Orphan Drugs ....................................................................................................... 134 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 139 Overview.................................................................................................................................... 139 NIH Guidelines.......................................................................................................................... 139 NIH Databases........................................................................................................................... 141 Other Commercial Databases..................................................................................................... 143 The Genome Project and Diazepam ........................................................................................... 143 APPENDIX B. PATIENT RESOURCES ............................................................................................... 147 Overview.................................................................................................................................... 147
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Patient Guideline Sources.......................................................................................................... 147 Finding Associations.................................................................................................................. 150 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 153 Overview.................................................................................................................................... 153 Preparation................................................................................................................................. 153 Finding a Local Medical Library................................................................................................ 153 Medical Libraries in the U.S. and Canada ................................................................................. 153 ONLINE GLOSSARIES................................................................................................................ 159 Online Dictionary Directories ................................................................................................... 161 DIAZEPAM DICTIONARY......................................................................................................... 163 INDEX .............................................................................................................................................. 237
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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 diazepam 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 diazepam, 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 diazepam, 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 diazepam. 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 diazepam, 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 diazepam. 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 DIAZEPAM Overview In this chapter, we will show you how to locate peer-reviewed references and studies on diazepam.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and diazepam, 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 “diazepam” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Review of Current Research on Midazolam and Diazepam for Endoscopic Premedication Source: Gastroenterology Nursing. 13(2 Supplement): 24S-28S. Fall 1990. Summary: This article reviews the current and past research on the use of midazolam and diazepam as endoscopic premedication. The pharmacology and mechanisms of action; use of the medications for endoscopic procedures; dosing schedules that are appropriate for the adult and elderly; and monitoring strategies to avert the cardiopulmonary complications that arise from the inattentive administration of these drugs are addressed. The author cites several research studies that have examined and compared the two medications during endoscopy, as well as in related medical fields. The author concludes that the short duration of action, short elimination half-life, and
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Diazepam
superior amnesic properties have made midazolam a popular alternative to diazepam. 28 references. (AA-M.)
Federally Funded Research on Diazepam The U.S. Government supports a variety of research studies relating to diazepam. 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 diazepam. 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 diazepam. The following is typical of the type of information found when searching the CRISP database for diazepam: •
Project Title: A 3-FACTOR MODEL OF DRUG EFFECTS ON OPERANT RESPONDING Principal Investigator & Institution: Gonzalez, Fernando A.; Morris Brown College 643 Martin Luther King Dr Nw Atlanta, Ga 30314 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-DEC-2005 Summary: (Applicant?s Abstract): Hermstein?s mathematical formulation of the matching law (1970) has been applied to data from operant conditioning procedures to disentangle the changes in responding attributable to drug-induced alterations in motivation from the changes attributable to drug-induced motor function impairment. The goal has been to develop an assay procedure and a classification system for the mode of behavioral action of drugs that have predictive value about the range of behavioral effects of drugs and their abuse potential. The behavioral procedure most often used in the studies is a Multiple Variable-Interval schedule (MultVI) consisting of five components that vary from 5 to 300 s. The generated response rate data are fitted by the single alternative equation of the matching law to obtain the value of the two parameters of the equation: k and rb. A common interpretation of k has been that it reflects, exclusively, the organism?s motor capacity to respond. The parameter rb is presumed to denote motivational factors. Results of studies conducted in our lab cast doubt on the above interpretation of the parameters. The same studies, however, confirm that k and rb are not affected by drugs in the same way, and that they may reveal different underlying actions of the drug. An alternative mathematical model, not burdened by theoretical implications of the matching law, is herein proposed. The model contains an additional parameter that reflects a third factor that underlies responding under operant procedures: stimulus control. Experiments will be conducted to test the validity of the proposed model by manipulating variables that affect (1)
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
facility to respond, (2) reinforcer efficacy and (3) stimulus control. The effects of acute injections of d-amphetamine, gammahydroxybutyrate, morphine, diazepam and pimozide on the parameters of the model will be studied with rats trained to respond under a six-component MultVI schedule. The effects of chronic administration of the drugs and the development of tolerance or sensitization as denoted by the three parameters will also be investigated. The project will provide minority undergraduates with research experience by involving them in all phases of the study as Research Assistants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADOLESCENT ETOH WITHDRAWAL: EFFECT ON ADULT RESPONSE Principal Investigator & Institution: Graham, Danielle L.; Psychology and Neuroscience; Baylor University Waco, Tx 76798 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: The overall objective of the present proposal is to examine the long-term effects of adolescent alcohol abuse. Specifically, this proposal is designed to examine the role of adolescent EtOH withdrawal on the aversive properties of EtOH in the mature animal. Study 1 will examine the role of adolescent ethanol withdrawal on the aversive properties of EtOH in adulthood, by alleviating the withdrawal response during adolescence. In this study, adolescent C3H mice will be exposed continuously or intermittently for 64 hours to EtOH vapor. Approximately four hours after removal from the inhalation chamber all animals will receive one of four IP injections of diazepam (0, 1, 2, or 3 mg/kg), which has previously been used to alleviate EtOH withdrawal. Six weeks following adolescent EtOH exposure all animals will be conditioned for an EtOH-induced condition taste aversion (CTA) response. Study 2 will be identical to the first with the exception that EtOH pre-exposure will occur during adulthood, rather than adolescence. Study 3 will examine the role of adolescent EtOH withdrawal on the aversive properties of EtOH in adulthood, by alleviating the withdrawal response during adult conditioning. In this study, two groups of adolescent C3H mice will be exposed to ethanol in the same manner as in Study 1 and 2. Six weeks following adolescent EtOH exposure, animals will be conditioned for an ethanol induced CTA. During conditioning animals will receive 15 minutes unlimited access to a.15% saccharin solution. Following the removal of the saccharin bottles, all animals will receive a 2.5-g/kg IP injection of EtOH. Approximately two hours following the EtOH injection, animals will also receive an EP injection of diazepam (0, 1, 2, or 3 mg/kg). Study 4 will be identical to Study 3 with the exception that EtOH pre-exposure will be administered during the adult period. Adolescent alcohol use and abuse is a significant problem. Findings from the proposed study will investigate the role that adolescent ethanol withdrawal plays on the aversive properties of ethanol in adulthood. These findings may have important implications with regard to the effects of adolescent alcohol abuse on EtOH-related behaviors in adulthood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AMYGDALAR NEUROPEPTIDES AND ANXIETY Principal Investigator & Institution: Wilson, Marlene A.; Professor; Pharmacology, Physiology and Neuroscience; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007
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Diazepam
Summary: (provided by applicant): The amygdala is a brain structure that plays a crucial role in fear and anxiety, and the actions of anxiety-reducing compounds. The opioid peptide has also been shown to modulate anxiety-related responses within the amygdala. Using herpes virus-mediated gene transfer, we have demonstrated that overexpression of enkephalin in the amygdala enhances the anxiety-reducing influences of the benzodiazepine diazepam (Valium) in rats. These initial results demonstrate that herpes virus-mediated gene transfer can transiently alter expression of neuropeptides in confined brain sites of adult rats, and that these changes can modify behavioral responses. The present studies continue to utilize this powerful technique to examine the role of amygdalar enkephalin in regulating anxiety-related behaviors and the actions of anxiolytic drugs. Both decreases and cell-targeted increases in peptide expression will be examined in several animal models of anxiety. Aim 1 will verify the ability of virusmediated gene transfer to decrease and cell-specifically increase expression of enkephalin in select areas of amygdala. Anatomical and quantitative methods will assess changes in mRNA expression, while peptide changes will be assessed with immunohistochemistry and radioimmunoassay. AIM 2 examines if altered enkephalin expression in central amygdala modifies anxiety-related behaviors in additional animal tests of anxiety behaviors and/or the effectiveness of other anxiolytics in these tests. These studies 1) compare decreases with cell-specific increases in enkephalin expression, 2) test the activity of other anxiolytics (alcohol, the serotonergic compound buspirone), and 3) tests effects in several models of anxiety. AIM 3 assesses the effects of pharmacological modulation of enkephalin activity in amygdala. Using more traditional techniques selective opioid receptor (mu, delta) agonists and antagonists will be locally applied in amygdala, and the effect of these compounds on responses to anxiolytic drugs will be tested. These studies will lead to a better understanding of the role of amygdala and enkephalin in anxiety and anxiolytic responses, as well as elucidate the differences between animal models of anxiety. This understanding may also suggest novel, avenues for development of treatments for anxiety or affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANXIOLYTIC DRUGS EFFECTS ON HIV1 NEUROPATHOGENESIS Principal Investigator & Institution: Lokensgard, James R.; Assistant Professor; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, Mn 55404 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 30-APR-2002 Summary: (Adapted from the Applicant's Abstract): Although the precise mechanisms whereby HIV-1 infection induces neurodegeneration have yet to be determined, a large body of evidence has incriminated glial cells and the production of proinflammatory mediators. For this reason, ideal therapeutic agents for the treatment of AIDS dementia would possess anti-inflammatory as well as anti-viral properties. Benzodiazepines, such as diazepam (Valium), are extensively prescribed drugs for anxiety disorders which readily cross the blood-brain barrier and have demonstrated immunomodulatory properties as well as antiviral activity in HIV-1-infected cell lines. In this application, the central hypothesis to be tested is that anxiolytic drugs attenuate HIV-1 neuropathogenesis through both inhibition of viral expression and suppression of brain cell-produced immune mediators. To characterize their inhibitory effects on HIV-1 expression in brain cells, human glial and mixed glial/neuronal cell cultures, as well as chronically infected promonocytes (U1 cells), will be infected with HIV-1 and maintained in the presence or absence of anxiolytic drugs. Expression of HIV-1 p24 Ag in culture supernatants will be quantified by ELISA. To test the hypothesis that the antiviral properties of anxiolytic drugs are mediated through an inhibition of cellular
Studies
7
transcription factor activation, nuclear extracts from HIV-1-infected human glial cells as well as U1 cells, incubated in the presence or absence of anxiolytic drugs, will be probed for nuclear factor kappa B (NF-kB) activation. To link the effects of anxiolytic druginduced inhibition of NK-kB with direct inhibition of HIV-1, transient transfection assays using HIV-1 promoter-reporter gene constructs, which contain either normal or mutated NF-kB consensus sequences, will be performed. To test the hypothesis that anxiolytic drugs attenuate HIV-1 neuropathogenesis by inhibiting the production of immune mediators, glial and mixed glial/neuronal cell cultures will be infected with HIV-1 and examined for the production of proinflammatory cytokines and betachemokines. The results of the proposed studies aims to contribute to a further understanding of HIV-1 neuropathogenesis and will hopefully have therapeutic implications regarding suppressing viral replication and neurodegeneration in HIV-1infected patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL INFLUENCES ON DRUG TOLERANCE Principal Investigator & Institution: Smith, James B.; Plant and Soil Science; Mercer University in Atlanta 3001 Mercer University Dr Atlanta, Ga 30341 Timing: Fiscal Year 2001; Project Start 19-JUL-1991; Project End 28-FEB-2006 Summary: Comparatively little is known about the ways in which behavioral factors themselves may influence the time course and extent of tolerance to behavioral effects of drugs. This project will attempt to more fully characterize the importance of behavioral factors during chronic administration of modulators at GABA and NMDA receptor sites, locations associated with activity for anxiolytics and psychotomimetics that are widely used on a chronic basis. The project will focus on operant behavior that is maintained (reinforced) by delivery of food and solutions of water & sucrose. This project is intended specifically to study influences on tolerance of: 1. Response Cost Experiments will study influences on tolerance by drug-produced changes in reinforcer frequency for varied response requirements, reinforcer magnitudes, and reinforcer types. 2. Operant Discriminations - Experiments will study influences on tolerance by discriminative properties of both the subjective effects of a drug as well as the environment in which the drug is chronically administered. Additionally, "multichamber" procedures will study generalization of those discriminative effects to performance of the same subjects in different circumstances. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BENZODIAZEPINE ACTIONS ON ALCOHOL REINFORCEMENT Principal Investigator & Institution: June, Harry L.; Associate Professor; Psychology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: (Adapted from the APPLICANTS ABSTRACT) The overall goal of this proposal is to identify and systematically examine benzodiazepine (BDZ) receptor ligands which attenuate the reinforcing properties of ethanol (ETOH). To accomplish this goal, the high alcohol drinking (HAD) rat and measures of ETOH reinforcement will be used. Quantitative receptor autoradiography (QAR) will also be used to determine if the binding affinity of effective BDZ ligands at central nervous system (CNS) sites correlates with the magnitude of behavioral effects. The main hypothesis to be tested is whether certain BDZ inverse agonist and antagonist ligands can selectively
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Diazepam
attenuate measures of ETOH reinforcement; this may be related to their binding at diazepam sensitive (DS), and to a lesser degree at diazepam insensitive (DI) conformations of GABAA-BDZ receptors. Initial dose-effect and time course studies will examine the ability of agents to attenuate ETOH intake using operant methodology. It is hypothesized that agents with high affinity for DS sites will be effective ETOH antagonists; however, agents with high affinity at both DS and DI sites should produce more potent and prolonged antagonism. In a second series of experiments, the threshold for electrical brain stimulation reward (BSR) will be compared in naive HAD and low alcohol drinking (LAD) rats. The role of oral (contingent) ETOH administration will also be tested for comparison with intra gastric (IG) (noncontingent) infusions in HAD rats. In addition, HAD and LAD rats will be compared for sensitivity to BSR following noncontingent ETOH administration. It is hypothesized that HAD rats will evidence a lower threshold and higher rate of responding for BSR compared with LAD rats under naive and following noncontingent ETOH. Contingent ETOH administration is expected to yield a more positive (euphoric) action on BSR compared with the noncontingent route in HAD rats. Studies of effective anti-ETOH agents using the optimal ETOH BSR threshold route will then be conducted in HAD rats. Using QAR, a third series of experiments will examine both inhibition and time course profiles of agents found effective as ETOH antagonists at CNS sites. It is hypothesized that highly effective ETOH antagonists should evidence greater binding at DS and DI sites hypothesized to mediate ETOH reinforcement, and that interactions at these sites may mediate in part (indirectly influence) activation of underlying neuroanatomical substrates contributing to the reinforcing properties of ETOH. It is further hypothesized that the behavioral and binding time course profiles will not be parallel. These studies should advance our understanding of the role the GABAA-BDZ receptor complex plays in mediating ETOH reinforcement, and may lead to the development of treatments for alcohol abuse and alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BENZODIAZEPINE-INDUCED GABAA RECEPTOR PLASTICITY Principal Investigator & Institution: Olsen, Richard W.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001 Summary: The GABA inhibitory synaptic system plays a major role in the central nervous system and is implicated in human neurological and psychiatric disorders such as epilepsy, stress, anxiety and panic disorders, sleep disorders, and drug dependence, especially to benzodiazepines and ethanol. The major postsynaptic GABA receptors involved in rapid inhibitory neurotransmission are the GABA/A receptors (GABA). GABAR proteins are subject to regulation at the level of transcription, translation, assembly, cell targeting, and the functional level. Endogenous regulation includes modulation by phosphorylation, zinc ions, and neuroactive steroids. GABAR are the known target of numerous clinically relevant drugs, including anti-epileptic antianxiety, and sedative/hypnotic/aesthetic agents. These include the widely used benzodiazepines, barbiturates, and possibly alcohol. GABAR are widely accepted as the major candidate molecular target of general anesthetic action. Their predominant role in the brain makes GABA likely players in the normal plasticity mechanisms that accompany ordinary and extraordinary experiences. By subjecting rats, or in some cases, cells, to somewhat extraordinary experiences that are considered to involve GABAR, we will investigate whether plastic changes in GABAR occur and the molecular and cellular mechanisms of the long-term modifications. In particular, chronic exposure of rats to
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benzodiazepines, but probably an elevation of GABAR function, leads to tolerance, especially to the anti-epileptic actions of these drugs. Tolerance is accompanied by a reduced GABAR function, reduced enhancement of GABAR function by benzodiazepines, and uncoupling of GABA- benzodiazepine binding measured in vitro. Tolerance to benzodiazepines can be mimicked in cells expressing recombinant GABAR that lack normal transcriptional control, and can be reversed rapidly by exposure in rats and in cells by exposure to the benzodiazepine antagonist flumazenil. This strongly suggests that the tolerance and reversal result from a physicochemical modification of the GABAR protein itself. This project will attempt to unearth this molecular mechanisms of plasticity. Ultimately therapeutic strategies could be based on our studies, aimed rationally at preventing the unwanted or pathological alterations in GABA/A receptors characteristic of several neurological and psychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BENZODIAZEPINES MECHANISMS
USE/ABUSE--EFFECTS
ON
MEMORY
Principal Investigator & Institution: Griffiths, Roland R.; Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: There is concern about the long-term use and abuse of benzodiazepine anxiolytic/hypnotic drugs by prescribed users and polydrug abusers. One of the most insidious adverse effects of benzodiazepines is memory impairment. This project involves a direct experimental investigation of the acute and chronic memory-impairing effects of benzodiazepines, guided by recent conceptual and methodological developments in human memory research. Experiment 1 will investigate the cognitive mechanisms underlying the well-established benzodiazepine-induced impairment in explicit memory (i.e., intentional or conscious recollection of a previous experience); this experiment will provide the first direct test of the hypothesis that benzodiazepines produce a specific impairment in memory for contextual information (i.e., information in the periphery of attention during an event), a phenomenon which plays a critical role in explicit memory. The acute contextual-memory effects of the benzodiazepine lorazepam will be compared to those of the anticholinergic drug scopolamine in healthy volunteers in a placebo-controlled double-blind independent groups design across a range of doses, using recently developed procedures for measuring effects on memory for contextual information. Experiments 2-3 will evaluate the acute effects of benzodiazepines on implicit memory (i.e., memory for a previous experience expressed unintentionally or without conscious recollection of the experience), a ubiquitous phenomenon with considerable theoretical and practical significance. The implicitmemory effects of lorazepam will be compared to those of scopolamine and the benzodiazepine diazepam in healthy volunteers in a placebo-controlled double-blind independent groups design across a range of doses, using recently developed procedures for measuring implicit memory. Experiment 4 will provide information of direct clinical relevance by evaluating explicit contextual memory and implicit memory in anxiety disorder-diagnosed individuals with long-term prescribed benzodiazepine use, relative to appropriately-matched control subjects. Data from this project will permit a more complete characterization of the effects of benzodiazepines on memory and will contribute to the understanding of the specificity of human memory processes. Ultimately, these data may also contribute to the development of improved drug abuse treatment strategies and to the development of anxiolytic/hypnotic compounds with reduced memory-impairing potential.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOFEEDBACK FOR FECAL INCONTINENCE AND CONSTIPATION Principal Investigator & Institution: Whitehead, William E.; Professor of Medicine; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 30-NOV-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CNS TRASMITTERS INVOLVED IN WITHRAWAL INDUCED ANXIETY Principal Investigator & Institution: Breese, George R.; Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001 Summary: Symptoms of withdrawal are believed to contribute significantly to sustaining alcoholism. Pharmacological evidence has been obtained that endogenous compounds, including a benzodiazepine (BZD)-inverse agonist, CRF, and glutamate, play a major role in withdrawal-induced anxiety, a symptom observed during withdrawal from chronic ethanol treatment (withdrawal). Further withdrawal produces changes in metabolic activity in specific regions of brain with are proposed to be due to release of endogenous transmitters which contribute to anxiety. In addition, comparison of male and female rats have revealed gender differences when rats were performing conflict tasks during withdrawal. From such data, we suggest the anxiety and increased metabolic activity observed during withdrawal are cause by an orchestrated release of these endogenous compounds that act on central BZD receptors (CBRs), peripheral BZD receptors (PBRs), CRF, and glutamate receptors and that this increased release during withdrawal is influence by gender. To gain support of this view, Specific Aim I will identify changes in metabolic activity using 2- deoxyglucose (2-DG) accumulation and Fos expression to identify brain areas involved in the anxiety response to a challenge with air puff or elevated-plus maze in male and female rats in the presence and absence of withdrawal. Subsequently, we will use antagonists of CRF, CBRs, PBRs and glutamate receptors and antisense deoxynucleotides for the peptides to see how specific metabolic events and the anxiety induced by ethanol withdrawal are affected. In specific Aim II, we will confirm and extend observations that the endogenous inverse agonist, diazepam binding inhibitor (DBI), which acts on CBRs and PBRs, as well as the CRF peptide is altered after chronic ethanol, during withdrawal, and when male and female rats are challenged with tasks reflecting anxiety during and in the absence of withdrawal. This determination will be made by measuring content of the peptides with radioimmunoassay or quantitative immunohistochemistry. The determination of the peptides will be coupled to measurement of their levels of mRNA within specific regions of brain using in situ hybridization. Specific Aim III will test the hypothesis that treatment with antagonists of the endogenous compounds, which blocked anxiety and central metabolic activity caused by a single withdrawal, will prevent sensitization of symptoms resulting from multiple withdrawals from chronic ethanol treatment. Once completed, these aims are expected to support the hypothesis that endogenous compounds acting on CBRs, PBRs, glutamate, or CRF receptors in specific regions of brain contribute to metabolic changes and to the anxiety to differing degrees in males
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and females during withdrawal from chronic ethanol exposure and that repeated withdrawals accentuate these withdrawal-induced changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--GENE DELIVERY Principal Investigator & Institution: Samulski, Richard J.; Director, Gene Therapy Center; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: A variety of virus vectors have established that effective gene delivery can be attained in non-dividing mammalian cells. For example, adeno- associated virus (AAV) vectors have been shown to stably transfer and express foreign genes in brain and muscle with little or no accompanying toxicity (McCown et al., 1996; Xiac et al., 1996). Based upon these advances, the present center grant will focus upon the use of AAV and adenovirus (AD) vectors to deliver and express genes proposed to ameliorate the adverse effects of chronic ethanol exposure, both in brain and liver. Therefore, the role of the vector core will be able to construct the cDNA cassettes, insert these cassettes into AAV of Ad vector plasmids, replicate and package the virus vectors, and finally test the function of the vectors, both in vitro and in vivo. Specifically, in Dr. Crews' section, AAV-tyrosine hydroxylase or tryptophan hydroxylase vectors will be prepared to test the involvement of dopaminergic and/or serotonergic function in rodent models of ethanol preference. In Dr. Thurman's section, AAV vectors will be prepared for the delivery of superoxide dismutase (SOD)/catalase, in order to evaluate the origin of ethanol induced oxidative damage to the liver, while Dr. Sulik will use the same AAV vectors to probe the mechanisms of ethanol teratogenicity. For Dr. Brenner, AD vectors will be prepared in order to identify the role of the immediate early genes, APl and NFkappaB, in ethanol-induced ethanol liver pathology. For Dr. Murrow, both sense and antisense AAV vectors will be prepared to delineate the role of GABAa receptor subunits in ethanol self administration, and finally, AAV vectors with antisense constructs to diazepam-binding inhibitor (DBI) and corticotrophan-releasing hormone (CRF) will be prepared for Dr. Breese to probe the role of these factors in the evolution of ethanol withdrawal anxiety. Thus, the vector core will provide the means to investigate molecular mechanisms directly involved in ethanol-induced pathologies, both in the brain and in the liver. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORRELATING DRUG EFFECTS ON THE VOR AND MOTION SICKNESS Principal Investigator & Institution: Kramer, Phillip D.; Instructor; Jfk Medical Center 65 James St Edison, Nj 08820 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Correlate diazeparn and meclizine's effects on the vestibular ocular reflex (VOR) with their ability to suppress motion sickness. Study design and methodology: Thirty subjects will have their vestibular (VOR gain, time constant, and reversal phase) and oculomotor function (gaze holding in the dark, OKN, and OKAN) tested at baseline and again two hours later. Immediately following the first set of tests the subject will ingest placebo, diazepam, meclizine, or nothing (randomized double blind order). After the second set of tests subjects will be exposed to a stimulus that promotes motion sickness. The subjects will make head movements while rotating
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at 120 deg/sec until they have reached a predetermined level of motion sickness defined by the Massachusetts Institute of Technology's modification of the Pensacola Diagnostic Index as Malaise III and note the number of head movements made until that point. Data will be examined for the correlation between the magnitude of the changes (with and without medication) of the VOR measurements and the difference in motion sickness susceptibility. The coefficients of a linear control system model of the vestibular and oculomotor systems will be manipulated to simulate the test results. The changes to the model may reflect functional localization of drug effects on the VOR, which may imply anatomical localization. Objectives: The vestibular system is a central component of both motion sickness and vestibular dizziness (vertigo) and both are treated with many of same medications including diazeparn and meclizine. Little is known, however, about their mechanisms of action in either motion sickness or vertigo. The objective of this study is to determine if diazeparn and meclizine's ability to prevent motion sickness is related to their ability to affect the VOR. This information is intended to help health care providers better treat patients with vertigo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL SCHIZOPHRENIA
MODELS
OF
GATING
DEFICITS
IN
Principal Investigator & Institution: Geyer, Mark A.; Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's Abstract) Isolation rearing of rats is a developmentally specific non-pharmacological manipulation that leads to deficits in sensorimotor gating, measured by prepulse inhibition of startle, that mimic those observed in schizophrenic patients. In rats, these gating deficits are reversed by both typical and atypical antipsychotic medications. The specific aims of this revised renewal application are to use the isolation rearing manipulation to better understand the neurobiological substrates underlying schizophrenia-spectrum disorders. In Aim 1 dose-response studies are proposed to further characterize the effects of selected pharmacological agents on isolation rearing effects in rats. First, the predictive validity of isolation-rearing-induced deficits in prepulse inhibition as a model of antipsychotic drug effects will be assessed by testing known antipsychotic drugs and drugs from other psychiatric treatment classes. Second, additional compounds having relatively selective actions at particular receptors will be examined to test hypotheses regarding the involvement of these particular receptors in the mediation of the behavioral effects of isolation rearing. Aim 2 studies will examine isolation rearing effects after manipulations of several neural substrates that are implicated in both the pathophysiology of schizophrenia and the regulation of prepulse inhibition, including the hippocampus, medial prefrontal cortex, striatum, and ventral pallidum. Neurochemically selective lesions and discrete microinjections of dopaminergic and serotonergic antagonists will be used to elucidate the neurobiological substrates of the isolation rearing induced gating deficit. Aim 3 will identify regionally specific neurochemical changes that are correlated specifically with isolation-induced deficits in prepulse inhibition. These hypotheses are closely linked to the questions being addressed using different methods in the Aim 2 studies. Thus, Aims 2 and 3 promise to provide converging evidence that should enable us to identify which parts of the circuitry known to regulate PPI are most relevant to the effects of isolation rearing on this animal model of the sensorimotor gating deficits observed in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENTAL NEUROSCIENCE RESEARCH GRANT Principal Investigator & Institution: Macleish, Peter R.; Professor; Anatomy; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 29-SEP-2002 Summary: This exploratory grant will establish the research infrastructure to facilitate the creation of a Neuroscience Research Center for the training of minority Neuroscientist at a historically black institution. The research program is focused around the central unifying theme of circadian rhythms. We plan to study the molecular mechanisms that determine circadian signal generation by the circadian oscillator and the influence of the circadian oscillator on motor mechanisms and behavior. The overall program is composed of four interrelated projects. Dr. Moore's project 1 will address the molecular mechanisms that generate and maintain autogenic circadian activity of the suprachiasmatic nucleus of the hypothalamus (SCN). These studies are designed to isolate and characterize SCN specific gene products that constitute components of the endogenous circadian oscillator. Identification of components of the circadian signal transduction pathways will facilitate subsequent elucidation of the molecular mechanisms that regulate their gene expression or specific activation. Dr. Moore's project 1 addresses the mechanisms by which the SCN control the synthesis and secretion of melatonin by the pineal gland. This project will also address the effect of melatonin on the synthesis of dopamine. Dr. Patrickson's project is designed to study the neuroanatomical substrates involved in circadian locomotor activity. Preliminary data suggest that circadian signals generated by the SCN are transmitted to the motor system by efferent neuronal projections. These studies will identify the SCN efferent projections and termination site(s) communicating circadian signals within the motor system. The significance of this/these site(s) in restoration of circadian locomotor activity by SCN implants in SCN lesioned animals will be evaluated. In the project 3 by Dr. Whittaker we examine the electrophysiological mechanisms in the circadian control of motor function. There is evidence that the release of dopamine within the basal ganglia exhibits a circadian pattern. This may infer a similar pattern of basal ganglia function. This project will study the distribution of dopamine (DA) and excitatory amino acids (EAA) receptors in the rat substantia nigra and the effects of circadian signals on these receptors. In addition, the humoral effects of melatonin on DA and EAA modulatory mechanisms in the substantia nigra will be investigated in brain slices using conventional current-clamp of nigral neurons as well as whole cell patch-clamp techniques. In project 4 (Dr. Moore) the relationship between circadian rhythms and behavior will be addressed. A unique resident- intruder conflict paradigm will be investigated to explore the role of variation in light/dark cycle, exogenous melatonin administration, diazepam and dopaminergic agents on social behavior, locomotor activity, and circadian rhythms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISCRIMINATIVE EFFECTS OF BENZODIAZEPINE WITHDRAWAL Principal Investigator & Institution: France, Charles P.; Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 15-MAR-1995; Project End 31-JAN-2002 Summary: (Adapted From The Applicant's Abstract) Benzodiazepines are among a growing set of compounds that exert many of their effects by actions at the gammaamino butyric acid (GABA)A receptor complex. Benzodiazepines are widely used for hypnosis and for anxiety-related disorders; however, long term use of these drugs can
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generate clinically-significant physical dependence. Moreover, there is increasing evidence for the co-abuse of benzodiazepines and other psychoactive drugs especially among individuals with a history of alcohol or sedative/hypnotic abuse. One major goal of this project is to develop a procedure for studying the discriminative stimulus (subjective) effects of benzodiazepine dependence and withdrawal in rhesus monkeys and, during the last period of support, such a procedure was developed. In the continuation of this project, separate groups of diazepam-treated, zolpidem-treated and untreated monkeys will be used to investigate three general issues using measures of drug discrimination, ventilation and neuroendocrine activity. First, GABAA modulators will be used to test hypotheses regarding selectivity of drug action and variations in efficacy. Although much is known about the molecular actions of GABAA modulators in vitro, very little is known about the clinical ramifications of those findings. These studies will provide a bridge from molecular studies to clinical applications by using a non-human primate model of subjective drug effects and physical dependence. Second, these experiments will expand the conditions under which discrimination procedures can be used to study dependence by establishing a flumazenil discrimination in monkeys receiving the novel GABAA modulator zolpidem, a drug that is widely prescribed for hypnosis. Third, "blind' drug evaluations will be conducted under the auspices of the CPDD. Collectively, these studies will provide fundamentally new information on the in vivo pharmacology of GABAA modulators and will help to identify the pharmacologic and behavioral determinants of physical dependence on sedative hypnotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISTINCTIVE INTEROCEPTIVE EFFECTS OF ALPHA 1 SELECTIVE GABA MODULATOR ZOLPIDEM Principal Investigator & Institution: Rowlett, James K.; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001 Summary: Zolpidem (Ambien ) is a commonly prescribed sleep-aid that exhibits selectivity for benzodiazepine (BZ)/GABAA receptors containing the alpha-1 subunit Previous studies have suggested that zolpidem has a characteristic profile of subjective effects that differ from those of conventional BZ agonists The present study assessed the ability of BZs and barbiturates, which typically share interoceptive effects with BZs, to reproduce the effects of zolpidem in squirrel monkeys trained to discriminate zolpidem from vehicle The effects of zolpidem also were assessed in squirrel monkeys trained to discriminate another sleep-aid, triazolam (Halcion ) Under test conditions, zolpidem engendered a dose-dependent increase in zolpidem-lever responding, reaching an average maximum of r80% Triazolam and diazepam also engendered r80% zolpidemlever responding However, other BZ agonists including chlordiazepoxide and lorazepam, as well as the barbiturates pentobarbital, bar bital, and methohexital, engendered maximums of only 20-70% zolpidem-lever responding up to doses that markedly reduced response rate In contrast, zolpidem, chlordiazepoxide and lorazepam substituted fully in monkeys trained to discriminate triazolam using a similar procedure These results suggest that zolpidem's selectivity for the alpha-1 subunit of the BZ/GABAA receptor complex confers a profile of interoceptive effects that is unique compared to typical BZ agonists Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUG ABUSE AND IMPULSIVITY: HUMAN LABORATORY MODELS Principal Investigator & Institution: De Wit, Harriet; Associate Professor; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 20-APR-1996; Project End 30-NOV-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUG ABUSE LIABILITY & SENSATION SEEKING Principal Investigator & Institution: Kelly, Thomas H.; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2006 Summary: (provided by applicant) This grant proposes five years of research to continue an ongoing investigation of sensation seeking status as a potential predictor of drug abuse in young adults. Prior epidemiological research has established a link between sensation-seeking (or novelty-seeking) behavior and drug abuse in humans. Research with rat models further suggests that novelty-seeking behavior is predictive of individual differences in dopamine function and in the reinforcing and other behavioral effects of drugs of abuse. Our ongoing studies have confirmed the predictive association between sensation-seeking status and individual differences in the behavioral effects of drugs with abuse liability in young adults. Reliable and substantial group differences on the sensation-seeking factor were insured as a result of the availability of the Lexington Longitudinal Database for recruitment of study participants. Currently, studies of the reinforcing, discriminative and other behavioral effects of d-amphetamine and diazepam are ongoing. We propose to continue these investigations and to extend this work to include other drugs with high abuse liability (marijuana, nicotine, alcohol, methylphenidate). In addition, the potential use of high sensation activities to modulate the behavioral effects of d-amphetamine will be investigated as a potential prevention intervention. Finally, since high- and low-sensation seekers have been shown to differ along a number of clinically important dimensions, we will begin investigations of the interrelationships among these dimensions by evaluating the extent to which predicts individual sensitivity to the behavioral effects of drugs with abuse liability. The wealth of data available in the Lexington Longitudinal Database (e.g., peer associations, school performance, prior drug use, family status, other intrapersonal factors) will also be available to examine individual differences in behavioral response to drugs with abuse liability, in addition to sensation seeking status. These studies will have important implications for understanding individual differences in risk for drug abuse, and may help to guide future prevention interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ETHANOL INTERACTIONS
AFFECTS
HYPOTHALAMIC-DENTATE
GYRUS
Principal Investigator & Institution: Wayner, Matthew J.; Div of Social and Policy Scis; University of Texas San Antonio San Antonio, Tx 78249 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: Our major working hypothesis has been that osmosensitive and glucosesensitive neurons of the lateral hypothalamus (LHA) that are involved in drinking and eating circuits are also sensitive to ethanol. These LHA circuits have embedded within
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them angiotensin (Ang) neurons that release Ang onto dentate gyrus granule cells and modulate synaptic plasticity in this brain region which plays an important role in learning and memory. This assumption is based upon the following facts. Angiotensin applied directly to the dentate gyrus inhibits long term potentiation (LTP) induction and the inhibition can be prevented by pretreating the animals with losartan, an Ang II AT1 receptor antagonist. LTP is a type of frequency-dependent synaptic plasticity. Ethanol drinking or ethanol applied directly to the LHA also inhibits LTP as well as impairs maze learning. Both the impairment of maze learning and LTP inhibition can be prevented by pretreatment with losartan. Because diazepam produces similar effects and these effects can also be prevented by pretreatment with losartan, we also assume that the ethanol triggering event in the LHA is mediated by GABAergic inhibitory interneurons. The specific aims of this proposal are: (a) To measure angiotensin release in the dentate gyrus before, during, and after various amounts of ethanol are applied either by intragastric intubulation or by direct pervasion to the LHA, (b) To determine the effects of diazepam and muscimol, a GABAA receptor agonist, on Ang release; and (c) To determine the relative effectiveness of bicuculline, a competitive GABAA antagonist, on Ang release when combined with 30 mM ethanol in the LHA perfusate. The expected results will provide critical data in support of our general hypothesis and establish a physiological meaningful neural circuit sensitive to ethanol with clearly identified afferents, a known neuromediator involved, and post synaptic effects important in cognitive processes associated with learning and memory. It will also provide a basis for expanding this research to identify other transmitters that might be released by these axon terminals. Losartan combined with diazepam might have therapeutic potential in treating alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GABAA RECEPTOR CHANNEL ALTERATION BY PROLONGED SEIZURES Principal Investigator & Institution: Mac Donald, Robert L.; Professor; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 20-JAN-2000; Project End 30-NOV-2001 Summary: (Verbatim from the Applicant's Abstract) While most partial and generalized seizures are relatively brief in duration, during some seizures, early termination fails and a prolonged epileptic state occurs that has been termed status epilepticus. Status epilepticus is relatively common, has a high morbidity and mortality and is a medical emergency requiring immediate treatment. Spontaneous seizure termination may involve activation of gamma-aminobutyric acid (GABA) receptor (GABAR)-mediated inhibition. If the GABAergic inhibition fails to terminate the seizure, a progressive reduction of GABAR-mediated inhibition develops that, when severe enough, results in a prolonged seizure. Status epilepticus in humans is treated acutely with benzodiazepines as well as barbiturates, which enhance GABAR-mediated inhibition. However, benzodiazepines are often efficacious early but not late in status epilepticus. We have shown that properties of dentate granule cell GABAR are altered during prolonged seizures in rats, with a reduction in benzodiazepine and zinc sensitivity without a change in GABA or pentobarbital sensitivity. These observations suggest that GABAR function changes during prolonged seizures, extending seizure duration and producing refractoriness to benzodiazepine treatment. Development of an understanding of this seizure-induced receptor plasticity would enhance understanding of spontaneous seizure termination and permit development of new treatment strategies
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for status epilepticus. The hypothesis to be tested is that during prolonged seizures, hippocampal dentate granule cell GABAR pharmacological and biophysical properties change due either to a change in receptor subtype composition or to receptor phosphorylation. The specific aims are to determine the : 1) dependence on seizure duration of development of insensitivity to benzodiazepines, 2) time course of development of decreased sensitivity of granule cell GABAR currents to diazepam and zinc, 3) sensitivity of granule cell GABAR currents GABAR modulators following prolonged seizures, 4) transient and steady state kinetic properties of granule cell GABAR single channel currents following prolonged seizures, 5) rate of recovery of regulation by diazepam and zinc of granule cell GABAR current following prolonged seizures, 6) rate of recovery of regulation by allosteric regulators of granule cell GABAR current following prolonged seizures, 7) dependence on PKA of recovery of granule cell GABAR current following prolonged seizures, 8) dependence on other kinases of recovery of granule cell GABAR current following prolonged seizures and 9) regulation of benzodiazepine, zinc and other allosteric regulator sensitivity of GABARs by phosphorylation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC VULNERABILITY TO DRUGS OF ABUSE Principal Investigator & Institution: Buck, Kari J.; Assistant Professor; Behavioral Neuroscience; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-AUG-1989; Project End 31-MAR-2004 Summary: Quantitative trait loci (QTLs) are chromosomal regions containing genes that influence a complex trait such as drug withdrawal severity. We have established that there is a great deal of common genetic influence on withdrawal from barbiturates, benzodiazepines, nitrous oxide, and alcohol. During the current period, we have mapped several QTLs that jointly have a major influence on the severity of pentobarbital (PB) withdrawal. The three largest QTLs are on mouse chrs 1, 4 and 11. QTLs in each of these regions have also been provisionally mapped for diazepam withdrawal, and definitively mapped for ethanol withdrawal: the chr 1 QTL was also provisionally mapped for nitrous oxide withdrawal. Using congenic strains to isolate each of the three QTLs against a uniform (inbred) genetic background, we propose to continue toward the eventual identification of the genes that underlie each PB withdrawal QTL. We propose to: (1) Test congenics for the strongest PB QTLs for their pleiotropic effects on withdrawal from other drugs of abuse; (2) Produce polycongenics in different combinations to determine whether gene-gene (epistatic) interactions are additive, potentiating in some combinations, or epistatic in some other way; (3) Narrow each QTL interval from our present approximately 20 cM to approximately 1 cM using interval specific congenic strains (ISCS); (4) Scan promising candidate genes for cDNA differences between B6 and D2 genotypes by SSCP; (5) Produce polycongenics from specific donor segment (SDS) congenics produced from appropriate interval specific congenic strains, and test for epistatic interactions among QTLs, as well as QTL pleiotropisms for withdrawal from other drugs, and for other drug-related responses known to be genetically correlated with PB withdrawal severity; and (6) Start with an F2 population, screen for additional QTLs not previously ascertained and produce additional congenics to facilitate eventual cloning of the genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GHB TOLERANCE AND DEPENDENCE Principal Investigator & Institution: Kuhn, Cynthia M.; Professor; Pharmacology and Cancer Biology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The purpose of this proposal is to investigate mechanisms of Gamma hydroxy butyrate (GHB) tolerance and dependence after chronic administration of low and high doses of GHB to rats. GHB is a novel sedative-hypnotic that is an emerging drug of abuse. GHB activates GHB, GABA-B and possibly GABA-A receptors, with a unique dose response relationship for each. When recreational users escalate use, tolerance develops and a withdrawal syndrome can occur that is characterized by insomnia, anxiety, and hallucinations. Tolerance and dependence to GHB are poorly characterized in animal models. We hypothesize that tolerance is related to dose and duration of exposure. We also hypothesize that the different receptor populations adapt at varying rates. We postulate that chronic treatment with lower doses or shorter regimens will cause tolerance at GHB and perhaps GABA-B receptors, while higher doses and longer treatments will lead to marked tolerance to GHB, GABA-A and GABA-B receptors. We will assess tolerance to GHB effects on sleep time, tilt plane and plus maze performance after chronic treatment with low or high doses for 7, 14 or 21 days. We will assess spontaneous and GHB (NCS-382) and GABA-B (CGP46381) antagonist-precipitated withdrawal by measuring sleep-wake cycle, locomotion as well as blood pressure and heart rate. Cross-tolerance to GABA-B (baclofen) and GABA-A (pentobarbital, diazepam) agonists will be assessed with the same behavioral measures. We will characterize inhibitory GHB mechanisms using electrophysiologic techniques in frontal cortex. GHB effects on spontaneous, evoked and mini GABA-A IPSCs and on postsynaptic potassium conductance will be determined. The effects of low and high GHB concentrations will be contrasted, and blockade by NCS-382 and CGP46381 on all parameters will be determined. Tolerance to specific GHB and GABA-B mechanisms will be studied by evaluating the same parameters in frontal cortex slices from animals treated chronically with low or high dose GHB. Finally, we will assess GHB effects on GABA-A receptors in naive and tolerant animals by measuring effects on GABA-mediated C1 uptake into synaptoneurosomes and its modulation by benzodiazepines, barbiturates and neurosteroids. These experiments should ultimately lead to the development of more effective pharmacotherapies for GHB dependence, which is an emerging drug abuse problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF DRUG DEPOSITION IN HAIR Principal Investigator & Institution: Ruth, James A.; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 15-MAY-1997; Project End 30-APR-2003 Summary: (Adapted from the application): Workplace drug testing has now become fairly commonplace as a surveillance procedure in the American workplace. Hair testing has the potential to offer numerous advantages over urine and serum testing; some of those being 1) reduced cost; 2) convenience of sample storage and shipment; and 3) reduced psychological stress for the test subject. Despite these potential advantages, hair testing, however, has yet to become an accepted procedure due to unresolved issues as: 1) efficacy of drug extraction from hair; 2) differentiation between drugs contacted externally on the hair versus drugs ingested and deposited via the systemic circulation;
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3) the effects of sweat and sebum on quantitation of hair drug levels; 4) correlation between ingested drug and distribution into hair; and 5) effects of pigment in hair deposition. The last issue may be the most important primarily because hair pigment in drug disposition has raised issues regarding differential sensitivity in and between various ethnic groups. In addition, gender bias may be significant when hair treatments such as dyes and salon treatments have the potential to remove or chemically alter or destroy deposited drugs. During the previous granting period, the investigators have accomplished the following objectives:(1) quantitation of hair growth rate via incorporating daily injections of rhodamine and measuring distance between fluorescent bands deposited in hair. Accessible water space was determined using a stage micrometer and equilibration of hairs with tritium oxide of known specific activity; (2) serum constituents as [C-14]urea, [Ca-45]calcium+2, [Cl-36]chloride- were quantitated and differences were noted in differentially pigmented hair; (3) highly covalently bound [S-35]cysteine was quantitated and a difference was noted in pigmented vs. lesspigmented hair. It was found that essentially no cysteine could be liberated on 24-hour extraction, consistent with possible covalent incorporation into hair matrix; (4) studies with fentanyl (as opposed to [H-3]-d-amphetamines and a benzoyl esterified amino alcohol, a model of cocaine) demonstrated that systemic delivery was not dose related, larger concentrations were extractable following external exposure, and "capping" of surface amino and hydroxyl groups resulted in significantly decreased, suggesting an interaction with hair chemical functionalities. Thus, a difference and a mechanism for fentanyl incorporation into hair via external and systemic route were semiquantitatively determined. Studies were also accomplished with labeled cocaine, nicotine, and flunitrazepam; and (5) sodium sulfide digestion resulted in significantly greater recovery of base-stable drugs than NaOH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS REINFORCEMENT
OF
OPIATE
AND
STIMULANT
DRUG
Principal Investigator & Institution: Ettenberg, Aaron; Associate Professor; Psychology; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2001; Project Start 01-MAR-1988; Project End 31-DEC-2002 Summary: (Applicant's Abstract) The primary long-term goal of this project is to employ behavioral pharmacological methods to investigate neura1 substrates underlying the self-administration of opiate and stimulant drugs of abuse. Toward this end, three specific aims are described each of which is intended to build upon and extend the work completed during the first nine years of this project. These are; 1) to continue investigations of the putative reward-attenuating actions of dopamine antagonist drugs on opiate- and stimulant-reinforced behaviors; 2) to further examine the role of drugpaired stimuli in drug self-administration and drug relapse; and 3) to continue investigations of the anxiogenic side effects of chronic cocaine. The hypothesis driving this work is that central dopaminergic (DA) systems are responsible for the reinforcing properties of both opiate and stimulant drugs. While this position is hardly unique, the methodological approach taken in this project is novel in a number of ways: I) while traditional lever-press procedures examine the behavior of drugged animals working to maintain their drug plasma levels, the current project examines IV drug reinforcement using an operant runway where animals received only one drug injection per day. In this context, the speed with which Ss traverse the alley for drug reinforcement has operationally provided a reliable index of the undrugged animals' motivation to obtain the reinforcer; ii) by testing only one trial per day, the resulting data are devoid of
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potential confounding and nonspecific effects produced by the drug reinforcers themselves; iii) a response reinstatement test is used to examine the factors that result in the reinstatement of operant runway behavior after a prolonged period of abstinence, and hence serves as a viable model of human drug relapse; and iv) in each of the studies, the putative reinforcement-attenuating actions of antagonist drugs are assessed at a time when the drug's direct pharmacological effects are no longer present (i.e., on the first post-treatment trial 24 hrs post-injection). This permits conclusions about antagonist effects on operant behavior that are not confounded by the sedative arrd motoric side-effects of these test agents. In summary, the work proposed in this application is intended to provide important new information about the nature and neurobiology of both the positive and negative factors that together determine the nature and extent of human drug self-administration behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBIOLOGY OF ANXIETY IN 5-HT1A RECEPTOR KNOCKOUT MICE Principal Investigator & Institution: Kirby, Lynn G.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Dysfunction of the serotonin (5-HT) and gammaaminobutyric acid (GABA) systems have been implicated in anxiety since most clinically useful anxiolytic compounds act by stimulating either 5-HT-1a or benzodiazepine receptors that modulate GABA neurotransmission. The specific brain regions involved and the particular interactions between 5-HT and GABA neurotransmitter systems during anxiety and its therapeutic treatment are not well understood. The long-term goal of this proposal is to understand the cellular and molecular substrates of anxiety as well as the specific neural circuits that may be affected in this disorder in order to identify novel targets for anxiolytic treatment. The objective of this application is to examine the particular fear and anxiety states resulting from alterations in the 5-HT and GABA systems in different brain regions using behavioral, electrophysiological and molecular techniques in an animal model of anxiety: the 5-HT-1a knockout (1AKO) mouse. In AIM 1 I will compare the behavior of 1aKOs and wild-type controls (WTs) to dorsal raphe nucleus (DRN) system-dependent vs. median raphe nucleus (MRN) system-dependent models of fear and anxiety. These studies will indicate the particular fear/anxiety states demonstrated by 1aKO mice as well as the particular circuits disrupted by the genetic deletion. I will then use electrophysiological and molecular techniques in AIMS 2 and 3 to test the specific alterations of 5-HT and GABA neurotransmission in different neural circuits in 1aKOs. In AIM 2 I will measure membrane characteristics, 5-HT-1a and GABAA receptor-mediated responses in DRN and MRN of 1aKOs and WTs using brain slice electrophysiological recording techniques. In AIM 3 I will measure 5-HT-1a and GABAA receptor-mediated responses in amygdala or hippocampal slices from 1aKOs and WTs. I will compare the measured electrophysiological response of the cell with its GABAA receptor subunit expression. My hypothesis is that deletion of the 5-HT-1a receptor disrupts 5-HT neurotransmission in specific cell bodies and their projections, altering GABA neurotransmission and ultimately producing the anxious phenotype. The experiments described in this proposal will elucidate neural circuits and altered neurotransmission that may underlie the particular anxiety states expressed by this animal model of anxiety. These experiments will lead to a better understanding of the interactions between the 5-HT
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and GABA systems during the expression of chronic anxiety and may identify potential targets for novel pharmacological treatments of anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBIOLOGY OF ANXIETY IN MICE LACKING 5HT 1A RECEPTOR Principal Investigator & Institution: Toth, Miklos; Associate Professor; Pharmacology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 23-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's Abstract) Functional abnormalities in the serotonin (5-HT) receptors have been consistently associated with anxiety. We have shown that inactivation of the 5-HTA receptor (5-HTAR) results in anxiety in mice. Surprisingly, we found that these mutant mice are insensitive to the anxiolytic effect of diazepam, a classical benzodiazepine (BZ). The importance of this finding is that a significant proportion of patients suffering from generalized anxiety do not respond to BZs. Also, BZs are not particularly effective in other forms of anxiety such as panic attacks and phobias. Since BZs bind and facilitate the function of the BZ sensitive gamma-aminobutyric acid receptors (GABAAR) receptors, abnormalities in these receptors could underlie the BZ-resistant anxiety and the anxiety-like behavior of the 5HTAR mutant mice. Indeed, we found abnormalities in the subunit composition of GABAARs in mutant mice. Our data show that the 5-HT and GABA systems, two important neurotransmitter systems implicated in anxiety disorders, are mechanistically linked. The objective of this application is to elucidate key features of the 5-HTARmediated regulation of GABAAR subunits that have a relevance to the KO phenotype and that could be applied to the understanding of anxiety. We ask the following questions: 1) Is the expression of the GABAAR subunits sensitive to the dosage of the 5HTA receptor? Anxiety in heterozygote KO mice suggests that GABAAR subunit expression is sensitive to 5-HTAR dosage. This would imply a pathogenic role for 5HTAR hypofunction described in panic anxiety. 2) Are the abnormal GABAAR subunit levels in 5-HTAR KO mice caused by a developmental arrest in subunit expression? Dysregulation of GABAAR subunits may occur during development because 5-HTAR represents a developmental signal in brain. 3) Are particular regions within amygdala and hippocampus of 5-HTAR KO mice specifically associated with altered GABAAR subunit expression? 4) Is GABA and glutamate release altered in the amygdala and hippocampus of 5-HTAR KO mice? These changes may occur to compensate GABAAR subunit abnormalities. 5) Can 5-HTA receptor agonists alter the expression of GABAAR subunits? Increasing signaling through the 5-HTAR by agonists may elicit GABAAR subunit changes that are beneficial in anxiety. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROPEPTIDE Y: ROLE IN ETHANOL INTAKE AND SENSITIVITY Principal Investigator & Institution: Thiele, Todd E.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAR-2005 Summary: Little is known of the role of regulatory neuropeptides in ethanol consumption and subsequent sensitivity to ethanol's effects. Neuropeptide Y (NPY), a 36-amino acid peptide, is distributed widely throughout the peripheral and central nervous systems, and is implicated in the control of many behaviors. We have investigated NPY-knockout mice and transgenic mice that overexpress NPY, and have
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found that ethanol consumption and resistance are inversely related to NPY levels. Proposed experiments will assess the hypothesis that ethanol and NPY share certain anxiolytic properties and that these interact to modulate ethanol consumption and ethanol-induced sedation. Specific experiments will address the following questions: (A) Which specific NPY receptors regulate the effects of NPY on ethanol intake and ethanolinduced sedation? To address this, voluntary ethanol consumption and ethanol-induced sedation will be assessed in mutant mice lacking specific central NPY receptors. (B) Where in the brain does NPY modulate voluntary ethanol consumption and the acute intoxicating effects produced by ethanol? This will be assessed by administering NPY into specific brain regions of NPY-knockout mice and assessing subsequent effects on ethanol consumption and sensitivity. (C) Does NPY modulate the rewarding and/or aversive effects of ethanol? To address this question, conditioned place preference learning and conditioned taste aversion learning following ethanol will be assessed in NPY-knockout mice and NPY-overexpressing mice. (D) Are the high ethanol consumption of NPY-knockout mice and the low ethanol consumption of NPYoverexpressing mice secondary to altered basal levels of anxiety? We will address this by manipulating anxiety levels in NPY-knockout and overexpressing mice and assessing subsequent effects on voluntary ethanol consumption. Additionally, we will determine if these mice have altered consumption of anxiolytic drugs other than ethanol. Determining how NPY acts to influence voluntary ethanol consumption and ethanol sensitivity is critical to a complete understanding of the neurobiological mechanisms that determine alcohol use and abuse. Such knowledge will be useful for the development of pharmacological treatments targeted at preventing excessive alcohol intake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL MEMS AND MICROFLUIDIC PLATFORMS FOR DRUG DELIVERY Principal Investigator & Institution: Siegel, Ronald A.; Professor; Pharmaceutics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): We propose to develop a suite of MEMS/microfluidic devices that will be useful for future drug delivery systems. Three projects are proposed: o In the first project, novel hydrogel/MEMS constructs will be produced. These constructs will provide a solid substrate that permits drug release rates to be modulated by a variety of signaling molecules. We will couple to MEMS substrates hydrogels whose permeability to macromolecules can be reversibly modulated by specific antigens. We will also develop new MEMS/hydrogel configurations which will expand the repertoire of this combination. 2. In the second project, a rapid microfluidic mixer will be used to produce supersaturated solutions of the antiepileptic drug, diazepam. These solutions are expected to remain stable long enough to be absorbed rapidly upon intranasal administration. The present work will test the hypothesis that the microfabicated mixer produces solutions of diazepam that will cross membranes much faster than solutions that are at phase equilibrium. 3. In the third project, a simple microfluidic device, which is expected to produce extremely uniform hydrogel microspheres, will be constructed and tested. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOLOGICAL TREATMENT OF ETHANOL WITHDRAWAL Principal Investigator & Institution: Gonzalez, Larry P.; Professor; Psychiatry and Behavioral Scis; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 30-JUN-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOLOGY OF BENZODIAZEPINE TOLERANCE AND DEPENDENCE Principal Investigator & Institution: Rosenberg, Howard C.; Professor and Chairman; Pharmacology and Therapeutics; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2001; Project Start 01-FEB-1985; Project End 30-JUN-2003 Summary: (Applicant's abstract) The tolerance and dependence associated with chronic benzodiazepine administration are complicated phenomena, probably due to the complex interactions between specific benzodiazepines and the many different types of GABA/benzodiazepine receptors. The literature suggests at least three types of adaptive processes that may be related to tolerance: those involving regulation of GABA/benzodiazepine receptor number, turnover, and subunit composition of receptors; those involving post-translational modifications of the receptor; and those involving secondary changes in other transmitter systems. It has been found that benzodiazepine treatment can affect benzodiazepine binding site number and GABAA receptor subunit mRNA levels, though the relationship to tolerance is not clear. Experiments will examine the effects of chronic benzodiazepine treatments of the levels of GABAA receptor beta subunits. Time and region-dependent changes will be compared to previous results from behavioral, biochemical, receptor bind, and mRNA studies. Adaptive changes in specific sub-populations of brain benzodiazepine receptors will be studied using recently-reported selective ligands. This will examine the hypothesis, based on previous results, that there is a shift in benzodiazepine receptor subtype in tolerant brain tissue. Other experiments will examine one type of posttranslational modification by evaluating a possible role for receptor glycosylation in regulating binding of selected drugs to the receptors, and the effects of chronic benzodiazepine treatment. The effect of deglycosylation on receptors is brain region specific, and differs for various benzodiazepines and other drugs that act at the GABA receptor. Thus, alterations in receptor glycosylation state could provide a basis for many of the changes found in GABA receptors during chronic benzodiazepine treatment. In each type of experiment, we will compare two chronic treatments (diazepam and flurozepam), as well as the time course of changes. This will provide the basis for evaluating the results in the context of previously- determined behavioral, biochemical and other measures of tolerance and dependence, and regulation of GABA/benzodiazepine receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSIOLOGIC ANALYSIS OF TWO GABAR GAMMA2-SUBUNIT DOMAINS Principal Investigator & Institution: Gallagher, Martin J.; Neurology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917
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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): This proposal describes a 5-year-training program for the development of an academic career in neurology and epilepsy. The principal investigator has completed residency training in neurology at Washington University in St. Louis and will complete a clinical epilepsy fellowship at Washington University in June 2002. He will then expand upon his scientific skills as an Assistant Professor of Neurology in the Epilepsy Division at Vanderbilt University Medical School. This program will promote the command of electro physiology, as applied to epilepsy. Robert L. Macdonald, MD, PhD will mentor the principal investigator's scientific development. Dr. Macdonald is a recognized leader in the field of electro physiology. He is the Chair of Neurology and has trained numerous K08 recipients, post-doctoral fellows and graduate students. In addition, close interaction with faculty in the Department of Neuroscience will provide additional scientific and career advice. Research will focus on the physiology and pharmacology of the gamma amino butyric acid receptor type A (GABAAR), the main fast inhibitory ion channel in the central nervous system. The GABAAR is the target of several anti-epileptic drugs, is associated with point mutations in at least two forms of human familial epilepsy, and is hypothesized will have an altered modulation by zinc in temporal lobe epilepsy. The proposed experiments entail construction of mutant and chimeric GABAARs, expressing the recombinant receptors in cultured cells, and determining their physiological kinetic parameters by rapid-application of drugs to macropatches and by analysis of single channel currents. The Specific Aims include: 1) evaluating the physiology GABAAR containing the point mutations found in human epilepsy, 2) determining the effect of allosteric modulators on the same GABAAR mutants, 3) determining the binding domains of zinc, and 4) determining the effect of GABAAR modulators on zinc inhibition. The Neurology Department at Vanderbilt University provides an ideal setting for training physician-scientists by incorporating expertise from diverse resources into customized programs. Such an environment maximizes the probability that the principal investigator will establish a scientific niche and embark upon a successful independent academic career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POSTOPERATIVE MUSCLE SPASM PAIN IN PEDIATRIC PATIENTS Principal Investigator & Institution: Leith, Phoebe J.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REINFORCING EFFECTS IN RHESUS MONKEYS Principal Investigator & Institution: Winger, Gail D.; Senior Research Scientist; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 20-JUN-1975; Project End 30-JUN-2006 Summary: (provided by applicant) This project uses monkeys with chronically indwelling intravenous catheters that can be used for passive drug administration, active drug self-administration and to take blood samples. When blood samples are taken, they will be analyzed for ACTH and cortisol levels. The goals of this project are first to determine the effects of acute administration of opioid drugs on the HPA axis,
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and to determine if increases in HPA axis activity can be used to measure acute naloxone-precipitated dependence to mu and kappa opioids. If so, the parameters of time following drug administration and the interval between drug injections will be evaluated to determine the role they play in the development of acute dependence. Second, the ability of breathing 5 percent CO2 and administration of 13 carboline ethyl ester to provoke a stress response as indicated by increases in ACTH will be measured. The ability of morphine and diazepam to attenuate each of these stress responses will be determined and compared. Morphine dependence will be produced in these animals and evidence for protracted abstinence will be looked for as a hyporeactivity of the HPA axis to 5 percent CO2 and 13CCE administration. Such a protracted abstinence reaction to restraint stress has been demonstrated in rats. The effects of self-administered opioids on the HPA axis will be established and compared with the effects previously observed with passive opioid administration. These effects of self-administered opioids on plasma levels of ACTH and cortisol will also be determined in animals with high "basal" levels of ACTH and cortisol as a result of either presession administration of 13CCE or opioid withdrawal. A procedure whereby demand functions are obtained in single 2-hr sessions will be used to determine if the elasticity of the demand function for shortacting opioid is decreased during opioid withdrawal. Finally, evaluation of the reinforcing effects of novel opioids as submitted by government agencies, academic, or industrial laboratories will continue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SELECTIVE ANXIOLYTICS VIA BZR SUBTYPE SPECIFIC LIGANDS Principal Investigator & Institution: Cook, James M.; Professor; Chemistry; University of Wisconsin Milwaukee Box 413, 2200 Kenwood Blvd Milwaukee, Wi 53201 Timing: Fiscal Year 2001; Project Start 01-SEP-1991; Project End 30-NOV-2005 Summary: Adapted from applicant's abstract): The understanding and treatment of pathological anxiety have long been a prime concern in regard to mental health. Alterations in GABAA function from controls are known to occur in anxiety disorders,6 including panic disorder, epilepsy,7 hypersensitive behavior,7b phobias,6 schizophrenia,8 alcoholism,9 Anglemans syndrome,7b and Rhetts syndrome,10 as well as effects which lead to/or complicate drug abuse.11 The 1,4-benzodiazepines, employed to treat anxiety disorders as well as sleep disorders exhibit anxiolytic, anticonvulsant, muscle relaxant/ataxic and sedative-hypnotic effects.5-12 Despite the clinical effectiveness of these drugs there is a need for selective anxiolytics and anticonvulsants which are devoid of myorelaxant/ataxic and sedative-hypnotic effects.5 Since BzR (benzodiazepine receptor) ligands allosterically modulate this system,1-5 the design of BzR subtype selective ligands5,25 is one means to generate better therapeutic agents.5 The combination of ligand affinities, molecular modeling and CoMFA analysis has been employed to determine the similarities and differences between BzR subtypes.25,26 This approach has permitted the synthesis of the most alpha5beta2gamma2 subtype selective agonist 5a reported to date,29 as well as several potent alpha5 selective inverse agonists 1a and 2a (50-75 fold more selective).25,28 Moreover, BCCt 6a (a neutral antagonist)31,32 and 3PBC 7a have been shown to be selective for alpha1beta2gamma2 subtypes, the former t-butylester is the most alpha1 selective agent in vitro reported to date.31,32 The alpha4/alpha6 "diazepaminsensitive" ligands 3a,b and 4a,b are again the most potent selective DI ligands reported to date. These ligands serve as lead compounds in the search for BzR subtype specific agents. Based on modeling, variation of the ligand substituents (chiral or achiral; polar or nonpolar) which occupy lipophilic pockets L1, L2, L3, or Ldi of the
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pharmacophore/receptor model will provide the desired subtype selectivity. The lead compounds are illustrated in Schemes I and II, while the target compounds are depicted in Schemes III-XI. The goal is to develop ligands that are > 150 times more selective for either alpha1,alpha5,alpha4, or alpha6 (later alpha2,alpha3) subtypes in order to determine which biological function is mediated by which subtype(s). Characterization of the pharmacology of BzR at the subtype level is crucial for understanding the physiological processes which underlie anxiety, including panic disorder,6 convulsions,7 sleep disorders and cognition,16 as well as the design of selective agents to treat these disease states with reduced abuse potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UNDERSTANDING STATUS EPILEPTICUS Principal Investigator & Institution: Kapur, Jaideep; Associate Professor; Neurology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2003 Summary: Status epilepticus (SE) is a neurologic emergency characterized by very prolonged, sometimes refractory seizures associated with a 23 percent mortality. SE is a progressive condition where seizures reduce GABA- medicated inhibition in the hippocampus which in turn leads to more seizures. Past and recent studies of patients and experimental animals having SE suggested the hypothesis that gamma-amino butyric acid type A (GABAA) receptor (GABAR) function is altered during SE. This proposal will directly test this hypothesis by using whole cell patch clamp to study the GABARs present on hippocampal neurons isolated from rats undergoing SE and by study of treatment of SE in rats. Experiments are proposed to accomplish following specific aims: 1) In whole animals the potency and efficacy of anticonvulsants acting at the benzodiazepine site and drugs acting at the barbiturate site of the GABARs will be measured after brief seizures and prolonged seizures of SE. 2) Compare the time course of loss of diazepam sensitivity of dentate granule cell GABARs during SE with the time course of loss of efficacy of diazepam in whole animals undergoing SE. 3) Compare the diazepam and pentobarbital sensitivity of CA1 pyramidal neurons acutely isolated from naive rats and rats undergoing 45 minutes of SE will be. 4) Characterize the detailed pharmacological properties of dentate granule cell GABARs following SE. 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 “diazepam” (or synonyms) into the search box. This search gives you access to full-
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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text articles. The following is a sample of items found for diazepam in the PubMed Central database: •
Basolateral Amygdala Lesions Block Diazepam-Induced Anterograde Amnesia in an Inhibitory Avoidance Task. by Tomaz C, Dickinson-Anson H, McGaugh JL.; 1992 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48919
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Cloning and Tissue-Specific Functional Characterization of the Promoter of the Rat Diazepam Binding Inhibitor, a Peptide with Multiple Biological Actions. by Kolmer M, Alho H, Costa E, Pani L.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47372
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Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. by Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M.; 2000 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27427
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Diazepam Binding Inhibitor is a Potent Cholecystokinin-Releasing Peptide in the Intestine. by Herzig K, Schon I, Tatemoto K, Ohe Y, Li Y, Folsch UR, Owyang C.; 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38851
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Diazepam Dependence Prevented by Glutamate Antagonists. by Steppuhn KG, Turski L.; 1993 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47038
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Diazepam-Binding Inhibitor (DBI)-Processing Products, Acting at the Mitochondrial DBI Receptor, Mediate Adrenocorticotropic Hormone-Induced Steroidogenesis in Rat Adrenal Gland. by Cavallaro S, Korneyev A, Guidotti A, Costa E.; 1992 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50388
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Diazepam-induced changes in sleep: Role of the [alpha]1 GABAA receptor subtype. by Tobler I, Kopp C, Deboer T, Rudolph U.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33491
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Diazepam-mediated inhibition of human immunodeficiency virus type 1 expression in human brain cells. by Lokensgard JR, Gekker G, Hu S, Arthur AF, Chao CC, Peterson PK.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164165
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Effects of diazepam on facial emotion recognition. by Coupland NJ, Singh AJ, Sustrik RA, Ting P, Blair RJ.; 2003 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=257795
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Frog Diazepam-Binding Inhibitor: Peptide Sequence, cDNA Cloning, and Expression in the Brain. by Lihrmann I, Plaquevent J, Tostivint H, Raijmakers R, Tonon M, Conlon JM, Vaudry H.; 1994 Jul 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44305
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Inhibition of Hormone-Stimulated Steroidogenesis in Cultured Leydig Tumor Cells by a Cholesterol-Linked Phosphorothioate Oligodeoxynucleotide Antisense to Diazepam-Binding Inhibitor. by Boujrad N, Hudson JR Jr, Papadopoulos V.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46795
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Molecular Cloning of the Gene for the Yeast Homolog (ACB) of Diazepam Binding Inhibitor/Endozepine/Acyl-CoA-Binding Protein. by Rose TM, Schultz ER, Todaro GJ.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50535
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Pregnenolone Biosynthesis in C6-2B Glioma Cell Mitochondria: Regulation by a Mitochondrial Diazepam Binding Inhibitor Receptor. by Papadopoulos V, Guarneri P, Krueger KE, Guidotti A, Costa E.; 1992 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49239
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Regulation of Pregnenolone Synthesis in C6-2B Glioma Cells by 4'- Chlorodiazepam. by Guarneri P, Papadopoulos V, Pan B, Costa E.; 1992 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49240
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 diazepam, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “diazepam” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for diazepam (hyperlinks lead to article summaries): •
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A case of gamma-hydroxybutyric acid withdrawal syndrome during alcohol addiction treatment: utility of diazepam administration. Author(s): Addolorato G, Caputo F, Capristo E, Bernardi M, Stefanini GF, Gasbarrini G. Source: Clinical Neuropharmacology. 1999 January-February; 22(1): 60-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10047936&dopt=Abstract
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A comparative evaluation of the effects of oral lorazepam, alprazolam and diazepam on venous admixture. Author(s): Naqib A, Mir B, Beigh A. Source: J Assoc Physicians India. 2002 March; 50: 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922228&dopt=Abstract
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A comparative study of clonidine versus a combination of diazepam and atropine for premedication in orthopaedic patients. Author(s): Chaurasia SK, Kane DG, Chaudhari LS. Source: Journal of Postgraduate Medicine. 1999 July-September; 45(3): 74-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734339&dopt=Abstract
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A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus. Author(s): Cock HR, Schapira AH. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 April; 95(4): 225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937649&dopt=Abstract
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A comparison of lorazepam, diazepam, and placebo for the treatment of out-ofhospital status epilepticus. Author(s): Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O'Neil N, Neuhaus JM, Segal MR, Lowenstein DH. Source: The New England Journal of Medicine. 2001 August 30; 345(9): 631-7. Erratum In: N Engl J Med 2001 December 20; 345(25): 1860. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547716&dopt=Abstract
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A comparison of metoclopramide and lidocaine for preventing pain on injection of diazepam. Author(s): Majedi H, Rabiee M, Khan ZH, Hassannasab B. Source: Anesthesia and Analgesia. 2002 November; 95(5): 1297-9, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401614&dopt=Abstract
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A comparison of midazolam and diazepam for conscious sedation during colonoscopy in a prospective double-blind study. Author(s): Zakko SF, Seifert HA, Gross JB. Source: Gastrointestinal Endoscopy. 1999 June; 49(6): 684-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10343209&dopt=Abstract
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A comparison of oral diazepam versus midazolam, administered with intravenous meperidine, as premedication to sedation for pediatric endoscopy. Author(s): Martinez JL, Sutters KA, Waite S, Davis J, Medina E, Montano N, Merzel D, Marquez C. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 July; 35(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142810&dopt=Abstract
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A comparison of rectal diazepam gel and placebo for acute repetitive seizures. Author(s): Dreifuss FE, Rosman NP, Cloyd JC, Pellock JM, Kuzniecky RI, Lo WD, Matsuo F, Sharp GB, Conry JA, Bergen DC, Bell WE. Source: The New England Journal of Medicine. 1998 June 25; 338(26): 1869-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9637805&dopt=Abstract
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A comparison of two oral ketamine-diazepam regimens for sedating anxious pediatric dental patients. Author(s): Reinemer HC, Wilson CF, Webb MD. Source: Pediatr Dent. 1996 July-August; 18(4): 294-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8857657&dopt=Abstract
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A comparison of two oral ketamine-diazepam regimens for the sedation of anxious pediatric dental patients. Author(s): Sullivan DC, Wilson CF, Webb MD. Source: Pediatr Dent. 2001 May-June; 23(3): 223-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11447952&dopt=Abstract
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A controlled evaluation of ibuprofen and diazepam for chronic orofacial muscle pain. Author(s): Singer E, Dionne R. Source: J Orofac Pain. 1997 Spring; 11(2): 139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332320&dopt=Abstract
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A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal. Author(s): Anton RF, Kranzler HR, McEvoy JP, Moak DH, Bianca R. Source: Psychopharmacology. 1997 May; 131(2): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9201799&dopt=Abstract
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A double-blind, placebo-controlled trial of abecarnil and diazepam in the treatment of patients with generalized anxiety disorder. Author(s): Rickels K, DeMartinis N, Aufdembrinke B. Source: Journal of Clinical Psychopharmacology. 2000 February; 20(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653203&dopt=Abstract
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A fugue-like state associated with diazepam use. Author(s): Simmer ED. Source: Military Medicine. 1999 June; 164(6): 442-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10377715&dopt=Abstract
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A human gene encoding diazepam-binding inhibitor/acy1-CoA-binding protein: transcription and hormonal regulation in the androgen-sensitive human prostatic adenocarcinoma cell line LNCaP. Author(s): Swinnen JV, Esquenet M, Rosseels J, Claessens F, Rombauts W, Heyns W, Verhoeven G. Source: Dna and Cell Biology. 1996 March; 15(3): 197-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8634149&dopt=Abstract
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A modified equilibrium dialysis technique for measuring plasma protein binding: experimental evaluation with diazepam and nortriptyline. Author(s): Chow HH, Khor SP, Lee HC, Mayersohn M. Source: Pharmaceutical Research. 1998 October; 15(10): 1643-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9794511&dopt=Abstract
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A modified simple and rapid reversed phase liquid chromatographic method for quantification of diazepam and nordiazepam in plasma. Author(s): Atta-Politou J, Parissi-Poulou M, Dona A, Koutselinis A. Source: Journal of Pharmaceutical and Biomedical Analysis. 1999 June; 20(1-2): 389-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704047&dopt=Abstract
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A preliminary study on oxygen saturation levels of patients during periodontal surgery with and without oral conscious sedation using diazepam. Author(s): Aeschliman SD, Blue MS, Williams KB, Cobb CM, MacNeill SR. Source: J Periodontol. 2003 July; 74(7): 1056-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931769&dopt=Abstract
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A prospective randomized trial comparing patient-controlled sedation using propofol and alfentanil and physician-administered sedation using diazepam and pethidine during transvaginal ultrasound-guided oocyte retrieval. Author(s): Lok IH, Chan MT, Chan DL, Cheung LP, Haines CJ, Yuen PM. Source: Human Reproduction (Oxford, England). 2002 August; 17(8): 2101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151444&dopt=Abstract
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A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Author(s): Lahat E. Source: Pediatric Emergency Care. 1997 December; 13(6): 449. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9435015&dopt=Abstract
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A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Author(s): Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y. Source: Pediatric Emergency Care. 1997 April; 13(2): 92-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9127414&dopt=Abstract
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A randomized comparison of low-dose ketamine and lignocaine infiltration with ketamine-diazepam anaesthesia for post partum tubal ligation in Vanuatu. Author(s): Grace RF, Lesteour T, Sala T, Stewart J. Source: Anaesthesia and Intensive Care. 2001 February; 29(1): 30-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261907&dopt=Abstract
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A randomized, prospective, double-blind comparison of midazolam (Versed) and emulsified diazepam (Dizac) for opioid-based, conscious sedation in endoscopic procedures. Author(s): Van Houten JS, Crane SA, Janardan SK, Wells K. Source: The American Journal of Gastroenterology. 1998 February; 93(2): 170-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9468235&dopt=Abstract
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A single-blind, crossover comparison of the pharmacokinetics and cognitive effects of a new diazepam rectal gel with intravenous diazepam. Author(s): Cloyd JC, Lalonde RL, Beniak TE, Novack GD. Source: Epilepsia. 1998 May; 39(5): 520-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9596205&dopt=Abstract
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A study of the sedative effect of home-administered oral diazepam for the dental treatment of children. Author(s): Yanase H, Braham RL, Fukuta O, Kurosu K. Source: International Journal of Paediatric Dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children. 1996 March; 6(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8695584&dopt=Abstract
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Absence of a pharmacokinetic interaction between quinidine and diazepam. Author(s): Rao BR, Rambhau D. Source: Drug Metabol Drug Interact. 1995; 12(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7555001&dopt=Abstract
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Abuse liability of diazepam through different routes. Author(s): Singh RK, Jain R, Ray R, Gupta YK. Source: Indian J Physiol Pharmacol. 2001 April; 45(2): 181-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480224&dopt=Abstract
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Acceptance of dental care following early extractions under rectal sedation with diazepam in preschool children. Author(s): Jensen B, Schroder U. Source: Acta Odontologica Scandinavica. 1998 August; 56(4): 229-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9765015&dopt=Abstract
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Airline passenger dies after being sedated.or to potentiating effects on diazepam. Author(s): Samer Abdalla M. Source: Bmj (Clinical Research Ed.). 1999 May 29; 318(7196): 1491. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10419304&dopt=Abstract
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Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam. Author(s): Lucht M, Kuehn KU, Armbruster J, Abraham G, Gaensicke M, Barnow S, Tretzel H, Freyberger HJ. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2003 March-April; 38(2): 168-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634266&dopt=Abstract
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Alertness and memory after sleep deprivation and diazepam intake. Author(s): Gorissen M, Tielemans M, Coenen A. Source: Journal of Psychopharmacology (Oxford, England). 1997; 11(3): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9305415&dopt=Abstract
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Alterations in cerebral diazepam binding inhibitor expression in drug dependence: a possible biochemical alteration common to drug dependence. Author(s): Ohkuma S, Katsura M, Tsujimura A. Source: Life Sciences. 2001 February 2; 68(11): 1215-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233989&dopt=Abstract
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Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men: subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. Author(s): Ciraulo DA, Barnhill JG, Ciraulo AM, Sarid-Segal O, Knapp C, Greenblatt DJ, Shader RI. Source: Journal of Clinical Pharmacology. 1997 January; 37(1): 64-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9048275&dopt=Abstract
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An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group. Author(s): Mitchell WG, Conry JA, Crumrine PK, Kriel RL, Cereghino JJ, Groves L, Rosenfeld WE. Source: Epilepsia. 1999 November; 40(11): 1610-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10565590&dopt=Abstract
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Analysis of homotropic and heterotropic cooperativity of diazepam oxidation by CYP3A4 using site-directed mutagenesis and kinetic modeling. Author(s): He YA, Roussel F, Halpert JR. Source: Archives of Biochemistry and Biophysics. 2003 January 1; 409(1): 92-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464248&dopt=Abstract
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Anomalous rectifying properties of 'diazepam-insensitive' GABA(A) receptors. Author(s): Granja R, Strakhova M, Knauer CS, Skolnick P. Source: European Journal of Pharmacology. 1998 March 26; 345(3): 315-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9592032&dopt=Abstract
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Application of solid-phase microextraction in the determination of diazepam binding to human serum albumin. Author(s): Yuan H, Pawliszyn J. Source: Analytical Chemistry. 2001 September 15; 73(18): 4410-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575786&dopt=Abstract
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Arterial oxygen saturation in Addis Ababa during diazepam-ketamine anaesthesia. Author(s): Streatfeild KA, Gebremeskel A. Source: Ethiop Med J. 1999 October; 37(4): 255-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961876&dopt=Abstract
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Assessment of diazepam loading dose therapy of delirium tremens. Author(s): Wasilewski D, Matsumoto H, Kur E, Dziklinska A, Wozny E, Stencka K, Skalski M, Chaba P, Szelenberger W. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 1996 May; 31(3): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8844033&dopt=Abstract
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Benzodiazepine receptor distribution and diazepam binding in schizophrenia: an exploratory study. Author(s): Schroder J, Bubeck B, Demisch S, Sauer H. Source: Psychiatry Research. 1997 February 7; 68(2-3): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9104759&dopt=Abstract
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Benzyl alcohol poisoning following diazepam intravenous infusion. Author(s): Lopez-Herce J, Bonet C, Meana A, Albajara L. Source: The Annals of Pharmacotherapy. 1995 June; 29(6): 632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7663039&dopt=Abstract
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Binding of fosphenytoin, phosphate ester pro drug of phenytoin, to human serum proteins and competitive binding with carbamazepine, diazepam, phenobarbital, phenylbutazone, phenytoin, valproic acid or warfarin. Author(s): Lai CM, Moore P, Quon CY. Source: Res Commun Mol Pathol Pharmacol. 1995 April; 88(1): 51-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7620838&dopt=Abstract
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Buccal midazolam and rectal diazepam for epilepsy. Author(s): Chattopadhyay A, Morris B, Blackburn L, Wassmer E, Whitehouse W. Source: Lancet. 1999 May 22; 353(9166): 1798. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10348017&dopt=Abstract
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Buccal midazolam and rectal diazepam for epilepsy. Author(s): Scheepers M, Comish S, Cordes L, Clough P, Scheepers B. Source: Lancet. 1999 May 22; 353(9166): 1797-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10348016&dopt=Abstract
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Buccal midazolam and rectal diazepam for epilepsy. Author(s): Ellis SJ, Baddely L. Source: Lancet. 1999 May 22; 353(9166): 1796-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10348015&dopt=Abstract
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Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Author(s): Camfield PR. Source: The Journal of Pediatrics. 1999 September; 135(3): 398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523148&dopt=Abstract
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Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Author(s): Scott RC, Besag FM, Neville BG. Source: Lancet. 1999 February 20; 353(9153): 623-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030327&dopt=Abstract
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Buspirone is differentiated from diazepam in humans using a three-response drug discrimination procedure. Author(s): Frey JM, Mintzer MZ, Rush CR, Griffiths RR. Source: Psychopharmacology. 1998 July; 138(1): 16-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9694522&dopt=Abstract
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Call for diazepam replacement. Author(s): Harris M. Source: Military Medicine. 2000 April; 165(4): Iii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802990&dopt=Abstract
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Call for diazepam replacement. Author(s): Harris M, Gausman D. Source: Military Medicine. 2000 February; 165(2): Ii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10709364&dopt=Abstract
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Cellular localization of the diazepam binding inhibitor (DBI) in the gastrointestinal tract of mice and its coexistence with the fatty acid binding protein (FABP). Author(s): Yanase H, Shimizu H, Kanda T, Fujii H, Iwanaga T. Source: Arch Histol Cytol. 2001 October; 64(4): 449-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757913&dopt=Abstract
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Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence. Author(s): Adinoff B, Anton R, Linnoila M, Guidotti A, Nemeroff CB, Bissette G. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1996 September; 15(3): 288-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8873112&dopt=Abstract
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Changes in “withdrawal symptoms” following discontinuation of low-dose diazepam. Author(s): Hayward P, Wardle J, Higgitt A, Gray J. Source: Psychopharmacology. 1996 June; 125(4): 392-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8826545&dopt=Abstract
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Clinical significance of methohexital, meperidine, and diazepam in breast milk. Author(s): Borgatta L, Jenny RW, Gruss L, Ong C, Barad D. Source: Journal of Clinical Pharmacology. 1997 March; 37(3): 186-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9089420&dopt=Abstract
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Clonidine and diazepam have differential effects on tests of attention and learning. Author(s): Coull JT, Middleton HC, Robbins TW, Sahakian BJ. Source: Psychopharmacology. 1995 August; 120(3): 322-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8524980&dopt=Abstract
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Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site. Author(s): Yang W, Drewe JA, Lan NC. Source: European Journal of Pharmacology. 1995 November 30; 291(3): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8719416&dopt=Abstract
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Combination fentanyl and diazepam for pediatric conscious sedation. Author(s): Pohlgeers AP, Friedland LR, Keegan-Jones L. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1995 October; 2(10): 879-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8542487&dopt=Abstract
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Comparative absorption kinetics of intramuscular midazolam and diazepam. Author(s): Hung OR, Dyck JB, Varvel J, Shafer SL, Stanski DR. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1996 May; 43(5 Pt 1): 450-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723850&dopt=Abstract
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Comparative audit of intravenous lorazepam and diazepam in the emergency treatment of convulsive status epilepticus in children. Author(s): Qureshi A, Wassmer E, Davies P, Berry K, Whitehouse WP. Source: Seizure : the Journal of the British Epilepsy Association. 2002 April; 11(3): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018955&dopt=Abstract
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Comparative study of intra-articular lidocaine and intravenous meperidine/diazepam for shoulder dislocations. Author(s): Orlinsky M, Shon S, Chiang C, Chan L, Carter P. Source: The Journal of Emergency Medicine. 2002 April; 22(3): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932085&dopt=Abstract
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Comparative study of oral clonidine and diazepam as premedicants in children. Author(s): Ramesh VJ, Bhardwaj N, Batra YK. Source: Int J Clin Pharmacol Ther. 1997 May; 35(5): 218-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9174878&dopt=Abstract
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Comparison of an ion-trap and a quadrupole mass spectrometer using diazepam as a model compound. Author(s): Fitzgerald RL, O'Neal CL, Hart BJ, Poklis A, Herold DA. Source: Journal of Analytical Toxicology. 1997 October; 21(6): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9323524&dopt=Abstract
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Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans. Author(s): Hellewell JS, Guimaraes FS, Wang M, Deakin JF. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(2): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475716&dopt=Abstract
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Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. Author(s): Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Source: Bmj (Clinical Research Ed.). 2000 July 8; 321(7253): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10884257&dopt=Abstract
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Comparison of psychomotor functions and sedation following premedication with oral diazepam and clonidine in children. Author(s): Jatti K, Batra YK, Bhardwaj N, Malhotra S. Source: Int J Clin Pharmacol Ther. 1998 June; 36(6): 336-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9660042&dopt=Abstract
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Comparison of psychomotor performance after intravenous and rectal diazepam. Author(s): Jensen HH, Hansen HC, Drenck NE. Source: Anesthesia Progress. 1997 Winter; 44(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9481974&dopt=Abstract
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Comparison of single- and repeated-dose pharmacokinetics of diazepam. Author(s): Walker MC, Tong X, Brown S, Shorvon SD, Patsalos PN. Source: Epilepsia. 1998 March; 39(3): 283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578046&dopt=Abstract
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Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man. Author(s): Bitsios P, Philpott A, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(3): 226-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512076&dopt=Abstract
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Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of Smephenytoin 4'-hydroxylation. Author(s): Ishizaki T, Chiba K, Manabe K, Koyama E, Hayashi M, Yasuda S, Horai Y, Tomono Y, Yamato C, Toyoki T. Source: Clinical Pharmacology and Therapeutics. 1995 August; 58(2): 155-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7648765&dopt=Abstract
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Comparison of triazolam, diazepam, and placebo as outpatient oral premedication for endodontic patients. Author(s): Ehrich DG, Lundgren JP, Dionne RA, Nicoll BK, Hutter JW. Source: Journal of Endodontics. 1997 March; 23(3): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9594761&dopt=Abstract
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Concentrations of cis(Z)-clopenthixol and trans(E)-clopenthixol in a lethal case involving zuclopenthixol, diazepam, and cyamemazine. Author(s): Rop PP. Source: Journal of Analytical Toxicology. 2001 July-August; 25(5): 348-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499890&dopt=Abstract
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Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. Author(s): Singhi S, Murthy A, Singhi P, Jayashree M. Source: Journal of Child Neurology. 2002 February; 17(2): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952069&dopt=Abstract
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Contrasting effects of clonidine and diazepam on tests of working memory and planning. Author(s): Coull JT, Middleton HC, Robbins TW, Sahakian BJ. Source: Psychopharmacology. 1995 August; 120(3): 311-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8524979&dopt=Abstract
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Control of eclamptic convulsions with rectal diazepam. Author(s): Povey WG. Source: Trop Doct. 1998 July; 28(3): 175. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700286&dopt=Abstract
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Controlling seizures in the prehospital setting: diazepam or midazolam? Author(s): Rainbow J, Browne GJ, Lam LT. Source: Journal of Paediatrics and Child Health. 2002 December; 38(6): 582-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410871&dopt=Abstract
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Detection of aneuploidy in rodent and human sperm by multicolor FISH after chronic exposure to diazepam. Author(s): Baumgartner A, Schmid TE, Schuetz CG, Adler ID. Source: Mutation Research. 2001 January 25; 490(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152967&dopt=Abstract
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Determination of benzodiazepin-1,4 derivatives in biological material. Part I. An attempt to apply high-performance liquid chromatography (HPLC) in the determination of diazepam and nitrazepam in human serum. Author(s): Welk B. Source: Acta Pol Pharm. 1996 January-February; 53(1): 3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8960277&dopt=Abstract
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Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse. Author(s): Cherry JA, Thompson BE, Pho V. Source: Biochimica Et Biophysica Acta. 2001 March 19; 1518(1-2): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267656&dopt=Abstract
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Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases. Author(s): Evans J, Levesque D, Knowles K, Longshore R, Plummer S. Source: J Vet Intern Med. 2003 May-June; 17(3): 304-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774970&dopt=Abstract
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Diazepam as an adjuvant analgesic to morphine for pain due to skeletal muscle spasm. Author(s): Srivastava M, Walsh D. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 January; 11(1): 66-9. Epub 2002 August 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527958&dopt=Abstract
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Diazepam binding inhibitor (DBI) in the plasma of pediatric and adult epileptic patients. Author(s): Ferrarese C, Cogliati T, Tortorella R, Zucca C, Bogliun G, Beghi E, Passoni D, Zoia C, Begni B, Airoldi L, Alho H, Frattola L. Source: Epilepsy Research. 1998 January; 29(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9477145&dopt=Abstract
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Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma. Author(s): Venturini I, Zeneroli ML, Corsi L, Baraldi C, Ferrarese C, Pecora N, Frigo M, Alho H, Farina F, Baraldi M. Source: Regulatory Peptides. 1998 April 24; 74(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9657356&dopt=Abstract
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Diazepam blocks fear-potentiated startle in humans. Author(s): Patrick CJ, Berthot BD, Moore JD. Source: Journal of Abnormal Psychology. 1996 February; 105(1): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8666715&dopt=Abstract
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Diazepam decreases performance in a long-term memory task using visual shapes. Author(s): Rosier A, Vogels R, Orban GA. Source: Neuroreport. 1996 August 12; 7(12): 1899-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8905688&dopt=Abstract
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Diazepam effects on the cerebral responses to tonic pain: a SPET study. Author(s): Di Piero V, Ferracuti S, Sabatini U, Tombari D, Di Legge S, Pantano P, Cruccu G, Lenzi GL. Source: Psychopharmacology. 2001 November; 158(3): 252-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713614&dopt=Abstract
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Diazepam enhancement of GABA-gated currents in binary and ternary GABAA receptors: relationship to benzodiazepine binding site density. Author(s): Granja R, Gunnersen D, Wong G, Valeyev A, Skolnick P. Source: Journal of Molecular Neuroscience : Mn. 1997 December; 9(3): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9481620&dopt=Abstract
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Diazepam enhances etoposide-induced cytotoxicity in U-87 MG human glioma cell line. Author(s): Lavicka J, Sarissky M, Mirossay A, Sulla I, Mojzis J, Mirossay L. Source: Fundamental & Clinical Pharmacology. 2001 June; 15(3): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468031&dopt=Abstract
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Diazepam for relief of irrigation pain after transurethral resection of the prostate. Author(s): Nott MR, Jameson PM, Julious SA. Source: European Journal of Anaesthesiology. 1997 March; 14(2): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088820&dopt=Abstract
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Diazepam in the treatment of GHB dependence. Author(s): Addolorato G, Caputo F, Capristo E, Gasbarrini G. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2001 February; 178: 183. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157447&dopt=Abstract
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Diazepam inhibits forskolin-stimulated adenylyl cyclase activity in human tumour cells. Author(s): Niles LP, Wang J. Source: Pharmacology & Toxicology. 1999 October; 85(4): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563512&dopt=Abstract
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Diazepam inhibits HIV-1 Tat-induced migration of human microglia. Author(s): Lokensgard JR, Hu S, Hegg CC, Thayer SA, Gekker G, Peterson PK. Source: Journal of Neurovirology. 2001 October; 7(5): 481-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11582521&dopt=Abstract
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Diazepam is more useful than magnesium for immediate control of eclampsia. Author(s): Fox R, Draycott T. Source: Bmj (Clinical Research Ed.). 1996 June 29; 312(7047): 1669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8664735&dopt=Abstract
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Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18 and P4502C19 as low K(M) diazepam N-demethylases. Author(s): Jung F, Richardson TH, Raucy JL, Johnson EF. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1997 February; 25(2): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9029042&dopt=Abstract
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Diazepam poisoning with one-month monitoring of diazepam and nordiazepam blood levels. Author(s): de Haro L, Valli M, Bourdon JH, Iliadis A, Hayek-Lanthois M, Arditti J. Source: Vet Hum Toxicol. 2001 June; 43(3): 174-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383664&dopt=Abstract
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Diazepam replacement. Author(s): Little JS. Source: Military Medicine. 2000 August; 165(8): 625. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10957858&dopt=Abstract
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Diazepam serum concentration-sedative effect relationship in patients with liver disease. Author(s): Bozkurt P, Kaya G, Suzer O, Senturk H. Source: Middle East J Anesthesiol. 1996 February; 13(4): 405-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8713635&dopt=Abstract
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Diazepam stimulates migration and phagocytosis of human neutrophils: possible contribution of peripheral-type benzodiazepine receptors and intracellular calcium. Author(s): Marino F, Cattaneo S, Cosentino M, Rasini E, Di Grazia L, Fietta AM, Lecchini S, Frigo G. Source: Pharmacology. 2001 July; 63(1): 42-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408831&dopt=Abstract
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Diazepam to reduce recurrences of febrile seizures. Author(s): Rosman NP. Source: The Journal of Pediatrics. 1996 February; 128(2): 303-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636838&dopt=Abstract
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Diazepam treatment of early signs of exacerbation in schizophrenia. Author(s): Carpenter WT Jr, Buchanan RW, Kirkpatrick B, Breier AF. Source: The American Journal of Psychiatry. 1999 February; 156(2): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9989567&dopt=Abstract
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Diazepam treatment to increase the cerebral GABAergic activity in acute stroke: a feasibility study in 104 patients. Author(s): Lodder J, Luijckx G, van Raak L, Kessels F. Source: Cerebrovascular Diseases (Basel, Switzerland). 2000 November-December; 10(6): 437-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11070373&dopt=Abstract
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Diazepam usage in veterans with spinal cord injury. Author(s): Broderick CP, Radnitz CL, Bauman WA. Source: J Spinal Cord Med. 1997 October; 20(4): 406-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9360221&dopt=Abstract
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Diazepam use during pregnancy: a review of the literature. Author(s): Iqbal MM, Sobhan T, Aftab SR, Mahmud SZ. Source: Del Med J. 2002 March; 74(3): 127-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11963349&dopt=Abstract
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Diazepam. Author(s): Lott DB. Source: Aorn Journal. 1996 February; 63(2): 349. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8907741&dopt=Abstract
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Diazepam-associated Sweet's syndrome. Author(s): Guimera FJ, Garcia-Bustinduy M, Noda A, Saez M, Dorta S, Sanchez R, Martin-Herrera A, Garcia-Montelongo R. Source: International Journal of Dermatology. 2000 October; 39(10): 795-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095204&dopt=Abstract
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Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function. Author(s): Cosentino M, Marino F, Cattaneo S, Di Grazia L, Francioli C, Fietta AM, Lecchini S, Frigo G. Source: Journal of Leukocyte Biology. 2000 May; 67(5): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811003&dopt=Abstract
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Diazepam-enhanced beta activity in Sturge Weber syndrome: its diagnostic significance in comparison with MRI. Author(s): Jansen FE, van Huffelen AC, Witkamp T, Couperus A, Teunissen N, Wieneke GH, van Nieuwenhuizen O. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 July; 113(7): 1025-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088695&dopt=Abstract
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Diazepam-mediated inhibition of human immunodeficiency virus type 1 expression in human brain cells. Author(s): Lokensgard JR, Gekker G, Hu S, Arthur AF, Chao CC, Peterson PK. Source: Antimicrobial Agents and Chemotherapy. 1997 November; 41(11): 2566-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9371370&dopt=Abstract
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Diazepam-omeprazole inhibition interaction: an in vitro investigation using human liver microsomes. Author(s): Zomorodi K, Houston JB. Source: British Journal of Clinical Pharmacology. 1996 August; 42(2): 157-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8864312&dopt=Abstract
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Diazepam-responsive neuroleptic malignant syndrome: a diagnostic subtype? Author(s): Miyaoka H, Shishikura K, Otsubo T, Muramatsu D, Kamijima K. Source: The American Journal of Psychiatry. 1997 June; 154(6): 882. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9167524&dopt=Abstract
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Different effects of lorazepam and diazepam on perceptual integration. Author(s): Beckers T, Wagemans J, Boucart M, Giersch A. Source: Vision Research. 2001 August; 41(17): 2297-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448721&dopt=Abstract
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Direct evidence for diazepam modulation of GABAA receptor microscopic affinity. Author(s): Lavoie AM, Twyman RE. Source: Neuropharmacology. 1996; 35(9-10): 1383-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014155&dopt=Abstract
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Dissociating neuromodulatory effects of diazepam on episodic memory encoding and executive function. Author(s): Coull JT, Frith CD, Dolan RJ. Source: Psychopharmacology. 1999 July; 145(2): 213-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463323&dopt=Abstract
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Driving under light and dark conditions: effects of alcohol and diazepam in young and older subjects. Author(s): Vanakoski J, Mattila MJ, Seppala T. Source: European Journal of Clinical Pharmacology. 2000 September; 56(6-7): 453-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11049006&dopt=Abstract
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Dual task performance after diazepam intake: can resource depletion explain the benzodiazepine-induced amnesia? Author(s): Gorissen ME, Eling PA. Source: Psychopharmacology. 1998 August; 138(3-4): 354-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725758&dopt=Abstract
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Educating lay carers of people with learning disability in epilepsy awareness and in the use of rectal diazepam: a suggested teaching protocol for use by healthcare personnel. Author(s): Sterrick M, Foley J. Source: Health Bull (Edinb). 1999 May; 57(3): 198-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811896&dopt=Abstract
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Effect of a single dose of diazepam on balance measures in older people. Author(s): Cutson TM, Gray SL, Hughes MA, Carson SW, Hanlon JT. Source: Journal of the American Geriatrics Society. 1997 April; 45(4): 435-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9100711&dopt=Abstract
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Effect of activated charcoal alone or given after gastric lavage in reducing the absorption of diazepam, ibuprofen and citalopram. Author(s): Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Source: British Journal of Clinical Pharmacology. 1999 August; 48(2): 148-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417490&dopt=Abstract
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Effect of diazepam on EEG power and coherent activity: sex differences. Author(s): Romano-Torres M, Borja-Lascurain E, Chao-Rebolledo C, del-Rio-Portilla Y, Corsi-Cabrera M. Source: Psychoneuroendocrinology. 2002 October; 27(7): 821-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183217&dopt=Abstract
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Effect of diazepam on plasma gamma-aminobutyric acid in sons of alcoholic fathers. Author(s): Cowley DS, Roy-Byrne PP, Greenblatt DJ, Kramer GL, Petty F. Source: Alcoholism, Clinical and Experimental Research. 1996 April; 20(2): 343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8730228&dopt=Abstract
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Effect of diazepam sedation on arterial oxygen saturation during esophagogastroduodenoscopy: a placebo-controlled study. Author(s): Gombar KK, Dhall JC, Suri RP, Singh B, Gombar S. Source: Indian J Gastroenterol. 1996 April; 15(2): 40-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8935931&dopt=Abstract
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Effect of oral diazepam on anal continence after low anterior resection: a preliminary study. Author(s): Maeda K, Maruta M, Sato H, Masumori K, Matsumoto M. Source: Techniques in Coloproctology. 2002 April; 6(1): 15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077635&dopt=Abstract
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Effect of sertraline on the pharmacokinetics and protein binding of diazepam in healthy volunteers. Author(s): Gardner MJ, Baris BA, Wilner KD, Preskorn SH. Source: Clinical Pharmacokinetics. 1997; 32 Suppl 1: 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9068935&dopt=Abstract
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Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects. Author(s): Qin XP, Xie HG, Wang W, He N, Huang SL, Xu ZH, Ou-Yang DS, Wang YJ, Zhou HH. Source: Clinical Pharmacology and Therapeutics. 1999 December; 66(6): 642-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613621&dopt=Abstract
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Effects of clonidine and diazepam on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man. Author(s): Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 23742. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769816&dopt=Abstract
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Effects of clonidine and diazepam on the acoustic startle response and on its inhibition by 'prepulses' in man. Author(s): Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 1997; 11(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9097890&dopt=Abstract
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Effects of clorazepate, diazepam, and oxazepam on a laboratory measurement of aggression in men. Author(s): Weisman AM, Berman ME, Taylor SP. Source: International Clinical Psychopharmacology. 1998 July; 13(4): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9727729&dopt=Abstract
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Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Author(s): Kosuge K, Jun Y, Watanabe H, Kimura M, Nishimoto M, Ishizaki T, Ohashi K. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 October; 29(10): 1284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560871&dopt=Abstract
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Effects of diazepam, baclofen and thiopental on the silent period evoked by transcranial magnetic stimulation in humans. Author(s): Inghilleri M, Berardelli A, Marchetti P, Manfredi M. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 1996 June; 109(3): 467-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8817277&dopt=Abstract
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Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro. Author(s): Heine J, Jaeger K, Weingaertner N, Scheinichen D, Marx G, Piepenbrock S. Source: Acta Anaesthesiologica Scandinavica. 2001 February; 45(2): 213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167168&dopt=Abstract
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Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. Author(s): Fisgin T, Gurer Y, Tezic T, Senbil N, Zorlu P, Okuyaz C, Akgun D. Source: Journal of Child Neurology. 2002 February; 17(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952072&dopt=Abstract
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Effects of nitrous oxide on diazepam sedation of young children. Author(s): Houpt MI, Kupietzky A, Tofsky NS, Koenigsberg SR. Source: Pediatr Dent. 1996 May-June; 18(3): 236-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8784916&dopt=Abstract
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Effects of oral diazepam on intravenous access in same day surgery patients. Author(s): Wittenberg MI, Lark TL, Butler CL, Handy RM, Schwanky HD, Tait AR, Tremper KK. Source: Journal of Clinical Anesthesia. 1998 February; 10(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9526931&dopt=Abstract
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Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia. Author(s): Robbins TW, Semple J, Kumar R, Truman MI, Shorter J, Ferraro A, Fox B, McKay G, Matthews K. Source: Psychopharmacology. 1997 November; 134(1): 95-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9399372&dopt=Abstract
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Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers. Author(s): Dixon R, Hughes AM, Nairn K, Sellers M, Kemp JV, Yates RA. Source: Cephalalgia : an International Journal of Headache. 1998 September; 18(7): 46875. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793699&dopt=Abstract
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Effects of the tranquillizer diazepam and the stimulant methylphenidate on alertness and memory. Author(s): Unrug A, Coenen A, van Luijtelaar G. Source: Neuropsychobiology. 1997; 36(1): 42-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9211444&dopt=Abstract
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Efficacy and safety of premedication with oral ketamine for day-case adenoidectomy compared with rectal diazepam/diclofenac and EMLA. Author(s): Filatov SM, Baer GA, Rorarius MG, Oikkonen M. Source: Acta Anaesthesiologica Scandinavica. 2000 January; 44(1): 118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669283&dopt=Abstract
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Eight inhibitory monoclonal antibodies define the role of individual P-450s in human liver microsomal diazepam, 7-ethoxycoumarin, and imipramine metabolism. Author(s): Yang TJ, Krausz KW, Sai Y, Gonzalez FJ, Gelboin HV. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1999 January; 27(1): 102-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9884317&dopt=Abstract
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Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers. Author(s): Lindhardt K, Gizurarson S, Stefansson SB, Olafsson DR, Bechgaard E. Source: British Journal of Clinical Pharmacology. 2001 November; 52(5): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736860&dopt=Abstract
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Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy. Author(s): Avallone R, Zeneroli ML, Venturini I, Corsi L, Schreier P, Kleinschnitz M, Ferrarese C, Farina F, Baraldi C, Pecora N, Frigo M, Baraldi M. Source: Gut. 1998 June; 42(6): 861-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9691927&dopt=Abstract
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Endogenous diazepam concentrations in the serum of patients with liver neoplasms. Author(s): Kopanski Z, Sliwinska M, Piekoszewski W, Habiniak J, Wojewoda T, Wojewoda A, Schlegel-Zawadzka M, Sibiga W. Source: Folia Histochem Cytobiol. 2001; 39 Suppl 2: 124-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820570&dopt=Abstract
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Establishment of a diazepam preference in human volunteers following a differential-conditioning history of placebo versus diazepam choice. Author(s): Alessi SM, Roll JM, Reilly MP, Johanson CE. Source: Experimental and Clinical Psychopharmacology. 2002 May; 10(2): 77-83; Discussion 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022801&dopt=Abstract
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Evaluation of treatment of hyperemesis gravidarum using parenteral fluid with or without diazepam. A randomized study. Author(s): Ditto A, Morgante G, la Marca A, De Leo V. Source: Gynecologic and Obstetric Investigation. 1999; 48(4): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10592423&dopt=Abstract
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Event-related potentials in a passive and active auditory condition: effects of diazepam and buspirone on slow wave positivity. Author(s): Unrug A, van Luijtelaar EL, Coles MG, Coenen AM. Source: Biological Psychology. 1997 August 22; 46(2): 101-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288408&dopt=Abstract
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Examining of changes in continuous GMK cell cultures treated with hydrocortisonum hemisuccinatum, propranolol and diazepam. Author(s): Mohamed BA. Source: Ann Univ Mariae Curie Sklodowska [med]. 1996; 51: 81-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9467252&dopt=Abstract
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Flumazenil reversal of conscious sedation induced with intravenous fentanyl and diazepam. Author(s): Finder RL, Moore PA, Close JM. Source: Anesthesia Progress. 1995; 42(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8934956&dopt=Abstract
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Flumazenil reversal of psychomotor impairment due to midazolam or diazepam for conscious sedation for upper endoscopy. Author(s): Kankaria A, Lewis JH, Ginsberg G, Gallagher J, al-Kawas FH, Nguyen CC, Fleischer DE, Benjamin SB. Source: Gastrointestinal Endoscopy. 1996 October; 44(4): 416-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8905360&dopt=Abstract
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Four amino acid exchanges convert a diazepam-insensitive, inverse agonist-preferring GABAA receptor into a diazepam-preferring GABAA receptor. Author(s): Wieland HA, Luddens H. Source: Journal of Medicinal Chemistry. 1994 December 23; 37(26): 4576-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7799410&dopt=Abstract
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Frequency domain source localization shows state-dependent diazepam effects in 47channel EEG. Author(s): Michel CM, Pascual-Marqui RD, Strik WK, Koenig T, Lehmann D. Source: Journal of Neural Transmission. General Section. 1995; 99(1-3): 157-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8579802&dopt=Abstract
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Gamma-hydroxybutyric acid and diazepam antagonize a rapid increase in GABA(A) receptors alpha(4) subunit mRNA abundance induced by ethanol withdrawal in cerebellar granule cells. Author(s): Follesa P, Mancuso L, Biggio F, Mostallino MC, Manca A, Mascia MP, Busonero F, Talani G, Sanna E, Biggio G. Source: Molecular Pharmacology. 2003 April; 63(4): 896-907. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644591&dopt=Abstract
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Gepirone and diazepam in generalized anxiety disorder: a placebo-controlled trial. Author(s): Rickels K, Schweizer E, DeMartinis N, Mandos L, Mercer C. Source: Journal of Clinical Psychopharmacology. 1997 August; 17(4): 272-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9241006&dopt=Abstract
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Haemodynamic effects of high-dose vecuronium compared with pancuronium in beta-blocked patients with coronary artery disease during fentanyl-diazepam-nitrous oxide anaesthesia. Author(s): Husby P, Gramstad L, Rosland JH, Vamnes JS, Segadal L. Source: Acta Anaesthesiologica Scandinavica. 1996 January; 40(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8904256&dopt=Abstract
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Hair analysis for nordiazepam and oxazepam by gas chromatography--negative-ion chemical ionization mass spectrometry. Author(s): Kintz P, Cirimele V, Vayssette F, Mangin P. Source: Journal of Chromatography. B, Biomedical Applications. 1996 March 3; 677(2): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8704927&dopt=Abstract
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Heat loss, sleepiness, and impaired performance after diazepam administration in humans. Author(s): Echizenya M, Mishima K, Satoh K, Kusanagi H, Sekine A, Ohkubo T, Shimizu T, Hishikawa Y. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 June; 28(6): 1198-206. Epub 2003 April 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700718&dopt=Abstract
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High-performance liquid chromatographic determination of diazepam in plasma of children with severe malaria. Author(s): Muchoh SN, Ogutu BR, Newton CR, Kokwar GO. Source: J Chromatogr B Biomed Sci Appl. 2001 September 25; 761(2): 255-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587356&dopt=Abstract
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Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19 and the 3A subfamily. Author(s): Ono S, Hatanaka T, Miyazawa S, Tsutsui M, Aoyama T, Gonzalez FJ, Satoh T. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1996 November; 26(11): 1155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8948091&dopt=Abstract
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Human methadone self-administration: effects of diazepam pretreatment. Author(s): Spiga R, Huang DB, Meisch RA, Grabowski J. Source: Experimental and Clinical Psychopharmacology. 2001 February; 9(1): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519634&dopt=Abstract
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Human, rat and crocodile liver microsomal monooxygenase activities measured using diazepam and nifedipine: effects of CYP3A inhibitors and relationship to immunochemically detected CYP3A apoprotein. Author(s): Reilly PE, Mason SR, Read MA. Source: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999 February; 122(2): 197-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10190045&dopt=Abstract
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Hypersensitivity to diazepam. Author(s): Asero R. Source: Allergy. 2002 December; 57(12): 1209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464054&dopt=Abstract
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Identification of diazepam-binding Inhibitor/Acyl-CoA-binding protein as a sterol regulatory element-binding protein-responsive gene. Author(s): Swinnen JV, Alen P, Heyns W, Verhoeven G. Source: The Journal of Biological Chemistry. 1998 August 7; 273(32): 19938-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9685328&dopt=Abstract
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Immediate effect of intravenous diazepam in neuroleptic-induced acute akathisia: an open-label study. Author(s): Hirose S, Ashby CR. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 524-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088165&dopt=Abstract
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Immunomodulating effects of tofizopam (Grandaxin) and diazepam in vitro. Author(s): Kalashnikov SV, Kalashnikova EA, Kokarovtseva SN. Source: Mediators of Inflammation. 2002 February; 11(1): 53-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926595&dopt=Abstract
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In vitro effects of diazepam on human ciliary function. Author(s): Johnston M, Watts S, Drake-Lee A. Source: Acta Oto-Laryngologica. 1997 November; 117(6): 856-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9442827&dopt=Abstract
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Increased expression of diazepam binding inhibitor in human brain tumors. Author(s): Alho H, Kolmer M, Harjuntausta T, Helen P. Source: Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research. 1995 March; 6(3): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794798&dopt=Abstract
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Increased expression of peripheral benzodiazepine receptors and diazepam binding inhibitor in human tumors sited in the liver. Author(s): Venturini I, Alho H, Podkletnova I, Corsi L, Rybnikova E, Pellicci R, Baraldi M, Pelto-Huikko M, Helen P, Zeneroli ML. Source: Life Sciences. 1999; 65(21): 2223-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576594&dopt=Abstract
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Influence of age, temperature, sex, height and diazepam on vibration perception. Author(s): Meh D, Denislic M. Source: Journal of the Neurological Sciences. 1995 December; 134(1-2): 136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8747856&dopt=Abstract
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Influence of diazepam and buspirone on human heart rate and the evoked cardiac response under varying cognitive load. Author(s): Unrug A, Bener J, Barry RJ, van Luijtelaar EL, Coenen AM, Kaiser J. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 1997 February; 25(2): 177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9101342&dopt=Abstract
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Influence of premedication with diazepam or morphine on the induction dose of eltanolone. Author(s): Czuchwicki A, Plummer JL, Love DR, Owen H, Ilsley AH. Source: Acta Anaesthesiologica Scandinavica. 1998 May; 42(5): 527-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9605367&dopt=Abstract
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Influence of sympathetic activity, temperature, ischemia and diazepam on thermal and vibration thresholds. Author(s): Meh D, Denislic M. Source: Pflugers Archiv : European Journal of Physiology. 1996; 431(6 Suppl 2): R305-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8739386&dopt=Abstract
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Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam. Author(s): Luurila H, Olkkola KT, Neuvonen PJ. Source: Pharmacology & Toxicology. 1996 February; 78(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8822046&dopt=Abstract
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Interaction between grapefruit juice and diazepam in humans. Author(s): Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A. Source: Eur J Drug Metab Pharmacokinet. 1998 January-March; 23(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9625273&dopt=Abstract
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Interethnic difference in omeprazole's inhibition of diazepam metabolism. Author(s): Caraco Y, Tateishi T, Wood AJ. Source: Clinical Pharmacology and Therapeutics. 1995 July; 58(1): 62-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7628184&dopt=Abstract
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Intracavernous application of diazepam: an alternative route of the seizure treatment-an experimental study in rabbits. Author(s): Dundaroz R, DeGim T, Sizlan A, Yasar M, Denli M, Gokcay E. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 April; 44(2): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896875&dopt=Abstract
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Intranasal administration of diazepam aiming at the treatment of acute seizures: clinical trials in healthy volunteers. Author(s): Gizurarson S, Gudbrandsson FK, Jonsson H, Bechgaard E. Source: Biological & Pharmaceutical Bulletin. 1999 April; 22(4): 425-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328567&dopt=Abstract
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Intranasal bioavailability of diazepam in sheep correlated to rabbit and man. Author(s): Lindhardt K, Olafsson DR, Gizurarson S, Bechgaard E. Source: International Journal of Pharmaceutics. 2002 January 1; 231(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719015&dopt=Abstract
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Intranasal midazolam for treating febrile seizures in children. Buccal midazolam for childhood seizures at home preferred to rectal diazepam. Author(s): Wassner E, Morris B, Fernando L, Rao M, Whitehouse WP. Source: Bmj (Clinical Research Ed.). 2001 January 13; 322(7278): 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203721&dopt=Abstract
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Intravenous diazepam for dissociative disorder: memory lost and found. Author(s): Ballew L, Morgan Y, Lippmann S. Source: Psychosomatics. 2003 July-August; 44(4): 346-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832603&dopt=Abstract
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Intravenous sedation for retrobulbar injection and eye surgery: diazepam and/or propofol? Author(s): Hampl KF, Marsch SC, Erb T, Drewe J, Schneider MC. Source: Acta Anaesthesiologica Scandinavica. 1996 January; 40(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8904260&dopt=Abstract
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In-vivo study of diazepam transfer across the first trimester human placenta. Author(s): Jauniaux E, Jurkovic D, Lees C, Campbell S, Gulbis B. Source: Human Reproduction (Oxford, England). 1996 April; 11(4): 889-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8671346&dopt=Abstract
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Is daily single dosage of diazepam as effective as chlordiazepoxide in divided doses in alcohol withdrawal--a pilot study. Author(s): Jauhar P, Anderson J. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2000 March-April; 35(2): 212-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10787400&dopt=Abstract
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Ketamine anesthesia with or without diazepam premedication for bone marrow punctures in children with acute lymphoblastic leukemia. Author(s): Tamminga RY, Noordhoek M, Kroon J, Faber-Nijholt R. Source: Pediatric Hematology and Oncology. 2000 July-August; 17(5): 383-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914048&dopt=Abstract
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Lack of pharmacokinetic interaction of pantoprazole with diazepam in man. Author(s): Gugler R, Hartmann M, Rudi J, Brod I, Huber R, Steinijans VW, Bliesath H, Wurst W, Klotz U. Source: British Journal of Clinical Pharmacology. 1996 August; 42(2): 249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8864328&dopt=Abstract
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Long-term intravenous and oral flumazenil treatment of acute diazepam overdose in an older patient. Author(s): Weinbroum A, Rudick V, Sorkine P, Fleishon R, Geller E. Source: Journal of the American Geriatrics Society. 1996 June; 44(6): 737-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8642175&dopt=Abstract
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Lorazepam and diazepam differently impair divided attention. Author(s): Jalava KM, Mattila MJ, Tarssanen M, Vanakoski J. Source: Pharmacology, Biochemistry, and Behavior. 1995 June-July; 51(2-3): 189-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7667327&dopt=Abstract
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Lorazepam and diazepam impair true, but not false, recognition in healthy volunteers. Author(s): Huron C, Servais C, Danion JM. Source: Psychopharmacology. 2001 May; 155(2): 204-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401011&dopt=Abstract
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Lorazepam but not diazepam impairs identification of pictures on the basis of specific contour fragments. Author(s): Wagemans J, Notebaert W, Boucart M. Source: Psychopharmacology. 1998 August; 138(3-4): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725755&dopt=Abstract
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Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Author(s): Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E. Source: Developmental Medicine and Child Neurology. 1995 August; 37(8): 682-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7672465&dopt=Abstract
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Maculopathy associated with diazepam. Author(s): Manners TD, Clarke MP. Source: Eye (London, England). 1995; 9 ( Pt 5): 660-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8543099&dopt=Abstract
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Magnesium sulphate versus diazepam for eclampsia. Author(s): Duley L, Henderson-Smart D. Source: Cochrane Database Syst Rev. 2000; (2): Cd000127. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796145&dopt=Abstract
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Magnesium sulphate versus diazepam in the management of eclampsia. Author(s): Shamsuddin L, Rouf S, Khan JH, Tamanna S, Hussain AZ, Samsuddin AK. Source: Bangladesh Med Res Counc Bull. 1998 August; 24(2): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9926482&dopt=Abstract
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Managing diazepam abuse in an AIDS-related psychiatric clinic with a high percentage of substance abusers. Author(s): Freedman JB, O'Dowd MA, McKegney FP, Kaplan IJ, Bernstein G, Biderman DJ, Gomez MF. Source: Psychosomatics. 1996 January-February; 37(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8600494&dopt=Abstract
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Massive dose of diazepam poisoning. Author(s): James M, Vijayalakshmi G, Das DG. Source: J Assoc Physicians India. 1998 November; 46(11): 972-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229229&dopt=Abstract
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Mechanism-based inhibition of rat liver microsomal diazepam C3-hydroxylase by mifepristone associated with loss of spectrally detectable cytochrome P450. Author(s): Reilly PE, Gomi RJ, Mason SR. Source: Chemico-Biological Interactions. 1999 March 1; 118(1): 39-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227577&dopt=Abstract
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Methodological considerations for the evaluation of EEG mapping data: a practical example based on a placebo/diazepam crossover trial. Author(s): Jahnig P, Jobert M. Source: Neuropsychobiology. 1995; 31(1): 31-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7708179&dopt=Abstract
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Microstate segmentation of spontaneous multichannel EEG map series under diazepam and sulpiride. Author(s): Kinoshita T, Strik WK, Michel CM, Yagyu T, Saito M, Lehmann D. Source: Pharmacopsychiatry. 1995 March; 28(2): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7624386&dopt=Abstract
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Midazolam versus diazepam in lipid emulsion as conscious sedation for colonoscopy with or without reversal of sedation with flumazenil. Author(s): Macken E, Gevers AM, Hendrickx A, Rutgeerts P. Source: Gastrointestinal Endoscopy. 1998 January; 47(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9468424&dopt=Abstract
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Modifications of diazepam binding inhibitor and peripheral benzodiazepine receptors in the lymphocytes of epileptic patients. Author(s): Ferrarese C, Perego M, Marzorati C, Bianchi G, Frigo M, Pecora N, Riva R, Moretti G, Frattola L. Source: Italian Journal of Neurological Sciences. 1996 April; 17(2): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8797068&dopt=Abstract
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Molecular cloning and chromosomal localization of a pseudogene related to the human acyl-CoA binding protein/diazepam binding inhibitor. Author(s): Gersuk VH, Rose TM, Todaro GJ. Source: Genomics. 1995 January 20; 25(2): 469-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7789980&dopt=Abstract
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Molecular cloning and expression of a novel human cDNA related to the diazepam binding inhibitor. Author(s): Suk K, Kim YH, Hwang DY, Ihm SH, Yoo HJ, Lee MS. Source: Biochimica Et Biophysica Acta. 1999 May 31; 1454(1): 126-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10354522&dopt=Abstract
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Molecular modulation of recombinant rat alpha1beta2gamma2 GABA(A) receptor channels by diazepam. Author(s): Krampfl K, Lepier A, Jahn K, Franke C, Bufler J. Source: Neuroscience Letters. 1998 November 13; 256(3): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9855360&dopt=Abstract
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Multisite kinetic models for CYP3A4: simultaneous activation and inhibition of diazepam and testosterone metabolism. Author(s): Kenworthy KE, Clarke SE, Andrews J, Houston JB. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 December; 29(12): 1644-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717184&dopt=Abstract
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Mutagenic activity of diazepam evaluated by in vivo cytogenetic tests. Author(s): Leal Garza CH, Valenciano Cedillo GG, Rojas Alvarado MA, Cortes Gutierrez EI. Source: Archives of Medical Research. 1998 Winter; 29(4): 285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9887544&dopt=Abstract
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Naltrexone effects on diazepam intoxication and pharmacokinetics in humans. Author(s): Swift R, Davidson D, Rosen S, Fitz E, Camara P. Source: Psychopharmacology. 1998 February; 135(3): 256-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498728&dopt=Abstract
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Neonatal flumazenil therapy reverses maternal diazepam. Author(s): Dixon JC, Speidel BD, Dixon JJ. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 February; 87(2): 225-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9512213&dopt=Abstract
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Nonconvulsive status epilepticus complicating neuroleptic malignant syndrome improved by intravenous diazepam. Author(s): Yoshino A, Yoshimasu H. Source: Journal of Clinical Psychopharmacology. 2000 June; 20(3): 389-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10831032&dopt=Abstract
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Omphalocele-exstrophy-imperforate-anus-spina bifida (OEIS) complex in a male prenatally exposed to diazepam. Author(s): Lizcano-Gil LA, Garcia-Cruz D, Sanchez-Corona J. Source: Archives of Medical Research. 1995 Spring; 26(1): 95-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7711456&dopt=Abstract
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Open trial study of a combined antidepressant (amitryptiline, perphenazine, diazepam) versus fluoxetine or imipramine in ambulatory depressed patients. Author(s): Diaz A, Fouilloux C, Ortiz S. Source: Proc West Pharmacol Soc. 2002; 45: 154-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434564&dopt=Abstract
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Optimisation and validation of a capillary electrophoresis method for the simultaneous determination of diazepam and otilonium bromide. Author(s): Furlanetto S, Orlandini S, Massolini G, Faucci MT, La Porta E, Pinzauti S. Source: The Analyst. 2001 October; 126(10): 1700-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693609&dopt=Abstract
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Oral midazolam compared with diazepam-droperidol and trimeprazine as premedicants in children. Author(s): Patel D, Meakin G. Source: Paediatric Anaesthesia. 1997; 7(4): 287-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9243685&dopt=Abstract
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Oral midazolam versus meperidine, atropine, and diazepam: a comparison of premedicants in pediatric outpatients. Author(s): Pywell CA, Hung YJ, Nagelhout J. Source: Aana Journal. 1995 April; 63(2): 124-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7740908&dopt=Abstract
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Paradoxic response to diazepam in complex partial status epilepticus. Author(s): Al Tahan A. Source: Archives of Medical Research. 2000 January-February; 31(1): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10767490&dopt=Abstract
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Paradoxical reactions to diazepam. Author(s): Smith VM. Source: Gastrointestinal Endoscopy. 1995 February; 41(2): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794361&dopt=Abstract
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Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and diazepam. Author(s): Troy SM, Lucki I, Peirgies AA, Parker VD, Klockowski PM, Chiang ST. Source: Journal of Clinical Pharmacology. 1995 April; 35(4): 410-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7650232&dopt=Abstract
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Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol. Author(s): van Steveninck AL, Gieschke R, Schoemaker RC, Roncari G, Tuk B, Pieters MS, Breimer DD, Cohen AF. Source: British Journal of Clinical Pharmacology. 1996 June; 41(6): 565-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8799523&dopt=Abstract
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Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions. Author(s): Ogutu BR, Newton CR, Crawley J, Muchohi SN, Otieno GO, Edwards G, Marsh K, Kokwaro GO. Source: British Journal of Clinical Pharmacology. 2002 January; 53(1): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849195&dopt=Abstract
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Pharmacological properties of recombinant “diazepam-insensitive” GABAA receptors. Author(s): Gunnersen D, Kaufman CM, Skolnick P. Source: Neuropharmacology. 1996; 35(9-10): 1307-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014146&dopt=Abstract
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Pharmacology of recombinant gamma-aminobutyric acidA receptors rendered diazepam-insensitive by point-mutated alpha-subunits. Author(s): Benson JA, Low K, Keist R, Mohler H, Rudolph U. Source: Febs Letters. 1998 July 24; 431(3): 400-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9714551&dopt=Abstract
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Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme. Author(s): Oudard S, Carpentier A, Banu E, Fauchon F, Celerier D, Poupon MF, Dutrillaux B, Andrieu JM, Delattre JY. Source: Journal of Neuro-Oncology. 2003 May; 63(1): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814259&dopt=Abstract
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Phenytoin-diazepam interaction. Author(s): Murphy A, Wilbur K. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 659-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708941&dopt=Abstract
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Pilot investigation of thyrotropin-releasing hormone-induced thyrotropin and prolactin release in anxious patients treated with diazepam. Author(s): Humbert T, Pujalte D, Bottai T, Hue B, Pouget R, Petit P. Source: Clinical Neuropharmacology. 1998 March-April; 21(2): 80-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579292&dopt=Abstract
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Position statement on the use of rectal diazepam in epilepsy. Epilepsy Society of Australia, the Child Neurology Study Group, the Australian Association of Neurologists, and the National Epilepsy Association of Australia. Author(s): Somerville ER, Antony JH. Source: The Medical Journal of Australia. 1995 September 4; 163(5): 268-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7565215&dopt=Abstract
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Possible inhibitory effect of diazepam on the metabolism of zotepine, an antipsychotic drug. Author(s): Kondo T, Tanaka O, Otani K, Mihara K, Tokinaga N, Kaneko S, Chiba K, Ishizaki T. Source: Psychopharmacology. 1996 October; 127(4): 311-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8923565&dopt=Abstract
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Potentiation of lonidamine and diazepam, two agents acting on mitochondria, in human glioblastoma treatment. Author(s): Miccoli L, Poirson-Bichat F, Sureau F, Bras Goncalves R, Bourgeois Y, Dutrillaux B, Poupon MF, Oudard S. Source: Journal of the National Cancer Institute. 1998 September 16; 90(18): 1400-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747871&dopt=Abstract
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Prefer diazepam for initial control of pre-eclamptic fits. Author(s): Fox R, Draycott T. Source: Bmj (Clinical Research Ed.). 1995 November 25; 311(7017): 1433. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8520290&dopt=Abstract
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Preference for diazepam, but not buspirone, in moderate drinkers. Author(s): Evans SM, Griffiths RR, de Wit H. Source: Psychopharmacology. 1996 January; 123(2): 154-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8741938&dopt=Abstract
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Preferences for ethanol and diazepam in anxious individuals: an evaluation of the self-medication hypothesis. Author(s): Chutuape MA, de Wit H. Source: Psychopharmacology. 1995 September; 121(1): 91-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8539345&dopt=Abstract
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Prehospital stability of diazepam and lorazepam. Author(s): Gottwald MD, Akers LC, Liu PK, Orsulak PJ, Corry MD, Bacchetti P, Fields SM, Lowenstein DH, Alldredge BK. Source: The American Journal of Emergency Medicine. 1999 July; 17(4): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10452426&dopt=Abstract
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Premedication with chlordemethyldiazepam and anxiolytic effect of diazepeam in implantology. Author(s): Manani G, Baldinelli L, Cordioli G, Consolati E, Luisetto F, Galzigna L. Source: Anesthesia Progress. 1995; 42(3-4): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8934975&dopt=Abstract
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Preventing febrile seizures in children with oral diazepam: can a controlled trial truly be “double-blind?”. Author(s): Rosman NP, Douglass LM, Paolini JL. Source: The Journal of Pediatrics. 2001 April; 138(4): 548-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295719&dopt=Abstract
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Prevention of urinary retention after general surgery: a controlled trial of carbachol/diazepam versus alfusozine. Author(s): Burger DH, Kappetein AP, Boutkan H, Breslau PJ. Source: Journal of the American College of Surgeons. 1997 September; 185(3): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9291399&dopt=Abstract
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Proactive interference and temporal context encoding after diazepam intake. Author(s): Gorissen ME, Curran HV, Eling PA. Source: Psychopharmacology. 1998 August; 138(3-4): 334-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725756&dopt=Abstract
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Promotes diazepam as safe, effective. Author(s): Hershberg PI. Source: The Journal of Family Practice. 1995 June; 40(6): 538. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7775903&dopt=Abstract
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Propylene glycol toxicity in a patient receiving intravenous diazepam. Author(s): Wilson KC, Reardon C, Farber HW. Source: The New England Journal of Medicine. 2000 September 14; 343(11): 815. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991709&dopt=Abstract
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PVC bags considerably reduce availability of diazepam. Author(s): Mahomed K, Nyamurera T, Tarumbwa A. Source: Cent Afr J Med. 1998 July; 44(7): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10028190&dopt=Abstract
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PVC bags considerably reduce availability of diazepam. Cent Afr J Med 1998;44(7) Author(s): Ball D, Tisocki K. Source: Cent Afr J Med. 1999 April; 45(4): 105. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746393&dopt=Abstract
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Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest. Author(s): Longstreth WT Jr, Fahrenbruch CE, Olsufka M, Walsh TR, Copass MK, Cobb LA. Source: Neurology. 2002 August 27; 59(4): 506-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196641&dopt=Abstract
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Randomized double-blind trial of psychotropic analgesic nitrous oxide compared with diazepam for alcohol withdrawal state. Author(s): Gillman MA, Lichtigfeld FJ. Source: Journal of Substance Abuse Treatment. 2002 April; 22(3): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12039615&dopt=Abstract
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Randomized, double-blind, placebo-controlled trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes. Author(s): Baumann BM, Perrone J, Hornig SE, Shofer FS, Hollander JE. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2000 August; 7(8): 878-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958127&dopt=Abstract
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Rapid and simple chromatographic method for the determination of diazepam and its major metabolites in human plasma and urine. Author(s): Azzam RM, Notarianni LJ, Ali HM. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 304-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653978&dopt=Abstract
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Rectal diazepam gel for treatment of acute repetitive seizures in adults. Author(s): Cereghino JJ, Cloyd JC, Kuzniecky RI; North American Diastat Study Group. Source: Archives of Neurology. 2002 December; 59(12): 1915-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470180&dopt=Abstract
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Rectal diazepam gel for treatment of acute repetitive seizures. The North American Diastat Study Group. Author(s): Kriel RL, Cloyd JC, Pellock JM, Mitchell WG, Cereghino JJ, Rosman NP. Source: Pediatric Neurology. 1999 April; 20(4): 282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328277&dopt=Abstract
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Rectal diazepam: pitfalls of excessive use in refractory epilepsy. Author(s): Brodtkorb E, Aamo T, Henriksen O, Lossius R. Source: Epilepsy Research. 1999 June; 35(2): 123-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372565&dopt=Abstract
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Rectal sedation with diazepam or midazolam during extractions of traumatized primary incisors: a prospective, randomized, double-blind trial in Swedish children aged 1.5-3.5 years. Author(s): Jensen B, Schroder U, Mansson U. Source: Acta Odontologica Scandinavica. 1999 August; 57(4): 190-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10540928&dopt=Abstract
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Reduction of oxazepam to desmethyldiazepam by human intestinal bacteria. Author(s): Okamura T, Sugiura W, Miyazawa M. Source: Biological & Pharmaceutical Bulletin. 1996 April; 19(4): 647-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9132177&dopt=Abstract
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Refractory status epilepticus in children: role of continuous diazepam infusion. Author(s): Singhi S, Banerjee S, Singhi P. Source: Journal of Child Neurology. 1998 January; 13(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9477244&dopt=Abstract
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Relation between bispectral index and plasma catecholamines after oral diazepam premedication. Author(s): Hirota K, Matsunami K, Kudo T, Ishihara H, Matsuki A. Source: European Journal of Anaesthesiology. 1999 August; 16(8): 516-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500939&dopt=Abstract
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Relationship of in vitro data on drug metabolism to in vivo pharmacokinetics and drug interactions: implications for diazepam disposition in humans. Author(s): Schmider J, Greenblatt DJ, von Moltke LL, Shader RI. Source: Journal of Clinical Psychopharmacology. 1996 August; 16(4): 267-72. Erratum In: J Clin Psychopharmacol 1996 October; 16(5): 344. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8835701&dopt=Abstract
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Respiratory depression in children receiving diazepam for acute seizures: a prospective study. Author(s): Norris E, Marzouk O, Nunn A, McIntyre J, Choonara I. Source: Developmental Medicine and Child Neurology. 1999 May; 41(5): 340-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10378761&dopt=Abstract
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Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam. Author(s): Yang TJ, Shou M, Korzekwa KR, Gonzalez FJ, Gelboin HV, Yang SK. Source: Biochemical Pharmacology. 1998 March 15; 55(6): 889-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9586962&dopt=Abstract
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Sedation by physician with diazepam for DC cardioversion of atrial arrhythmias. Author(s): Pugh PJ, Spurrell P, Kamalvand K, Sulke AN. Source: Heart (British Cardiac Society). 2001 November; 86(5): 572-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602558&dopt=Abstract
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Sedation for enteroclysis using oral diazepam. Author(s): Gold B, Smith G. Source: Ajr. American Journal of Roentgenology. 1996 December; 167(6): 1591. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8956606&dopt=Abstract
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Sedation for upper gastrointestinal endoscopy: a comparison of alfentanil-midazolam and meperidine-diazepam. Author(s): Donnelly MB, Scott WA, Daly DS. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1994 December; 41(12): 1161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7867109&dopt=Abstract
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Selective impairment in the recognition of anger induced by diazepam. Author(s): Blair RJ, Curran HV. Source: Psychopharmacology. 1999 December; 147(3): 335-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639695&dopt=Abstract
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Sensitivity of the fear-inhibited light reflex to diazepam. Author(s): Bitsios P, Szabadi E, Bradshaw CM. Source: Psychopharmacology. 1998 January; 135(1): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9489938&dopt=Abstract
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Serum diazepam levels after oral administration in children. Author(s): Visudtibhan A, Chiemchanya S, Visudhiphan P, Kanjanarungsichai A, Kaojarern S, Pichaipat V. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1065-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549777&dopt=Abstract
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Severe and prolonged sedation in five neonates due to persistence of active diazepam metabolites. Author(s): Peinemann F, Daldrup T. Source: European Journal of Pediatrics. 2001 June; 160(6): 378-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421420&dopt=Abstract
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Severe vasculitis after therapy with diazepam. Author(s): Olcina GM, Simonart T. Source: The American Journal of Psychiatry. 1999 June; 156(6): 972-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360151&dopt=Abstract
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Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: a comparison between midazolam, diazepam, and lorazepam. Author(s): Agelink MW, Majewski TB, Andrich J, Mueck-Weymann M. Source: Critical Care Medicine. 2002 May; 30(5): 997-1006. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006794&dopt=Abstract
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Sigmoidal kinetic model for two co-operative substrate-binding sites in a cytochrome P450 3A4 active site: an example of the metabolism of diazepam and its derivatives. Author(s): Shou M, Mei Q, Ettore MW Jr, Dai R, Baillie TA, Rushmore TH. Source: The Biochemical Journal. 1999 June 15; 340 ( Pt 3): 845-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10359672&dopt=Abstract
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Simultaneous modeling of the pharmacokinetics and pharmacodynamics of midazolam and diazepam. Author(s): Mould DR, DeFeo TM, Reele S, Milla G, Limjuco R, Crews T, Choma N, Patel IH. Source: Clinical Pharmacology and Therapeutics. 1995 July; 58(1): 35-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7628181&dopt=Abstract
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Skeletal muscle uptake of fluorine-18-FDG: effect of oral diazepam. Author(s): Barrington SF, Maisey MN. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1996 July; 37(7): 1127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965182&dopt=Abstract
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Solvent-modified solid-phase microextraction for the determination of diazepam in human plasma samples by capillary gas chromatography. Author(s): Krogh M, Grefslie H, Rasmussen KE. Source: J Chromatogr B Biomed Sci Appl. 1997 February 21; 689(2): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9080322&dopt=Abstract
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Stability of diazepam rectal gel in ambulance-like environments. Author(s): Alldredge BK, Venteicher R, Calderwood TS. Source: The American Journal of Emergency Medicine. 2002 March; 20(2): 88-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880869&dopt=Abstract
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Studies on psychomotor performance in healthy volunteers after diazepam, propranolol and alcohol given alone or in combination. Author(s): Khajuria V, Kapoor B, Raina RK. Source: Indian J Physiol Pharmacol. 1995 July; 39(3): 242-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8550117&dopt=Abstract
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Studies on quantitative beta activity in EEG background changes produced by intravenous diazepam in epilepsy. Author(s): Huang ZC, Shen DL. Source: Clin Electroencephalogr. 1997 July; 28(3): 172-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9241472&dopt=Abstract
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Sublingual triazolam versus peroral diazepam as a premedication for general anaesthesia. Author(s): Penttila HJ, Nuutinen LS, Kiviluoma KT, Partanen AM. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1995 October; 42(10): 862-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8706194&dopt=Abstract
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Sufentanil with and without diazepam for coronary artery bypass graft surgery. Author(s): Lina AA, Dauchot PJ, Anton AH. Source: Acta Anaesthesiol Belg. 1996; 47(4): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9093645&dopt=Abstract
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Syndrome of inappropriate secretion of antidiuretic hormone complicating neonatal diazepam withdrawal. Author(s): Nako Y, Tachibana A, Harigaya A, Tomomasa T, Morikawa A. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 April; 89(4): 488-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830465&dopt=Abstract
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Systemic contact dermatitis due to intravenous Valium in a person sensitive to propylene glycol. Author(s): Fisher AA. Source: Cutis; Cutaneous Medicine for the Practitioner. 1995 June; 55(6): 327-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7648882&dopt=Abstract
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The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery. Author(s): Wilner KD, Anziano RJ, Johnson AC, Miceli JJ, Fricke JR, Titus CK. Source: Journal of Clinical Psychopharmacology. 2002 April; 22(2): 206-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910268&dopt=Abstract
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The assessment of residual effects of a single dose of diazepam on visually-defined EEG patterns. Author(s): Sierra JC, Luna-Villegas G, Buela-Casal G, Fernandez-Guardiola A. Source: Journal of Psychopharmacology (Oxford, England). 1997; 11(4): 367-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443527&dopt=Abstract
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The characterization of two diazepam binding inhibitor (DBI) transcripts in humans. Author(s): Kolmer M, Rovio A, Alho H. Source: The Biochemical Journal. 1995 March 1; 306 ( Pt 2): 327-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7534063&dopt=Abstract
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The effect of diazepam and promethazine treatment during pregnancy on the somatic development of human offspring. Author(s): Czeizel AE, Szegal BA, Joffe JM, Racz J. Source: Neurotoxicology and Teratology. 1999 March-April; 21(2): 157-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192276&dopt=Abstract
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The effect of diazepam on motor cortical oscillations and corticomuscular coherence studied in man. Author(s): Baker MR, Baker SN. Source: The Journal of Physiology. 2003 February 1; 546(Pt 3): 931-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563016&dopt=Abstract
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The effect of the antimycotic itraconazole on the pharmacokinetics and pharmacodynamics of diazepam. Author(s): Ahonen J, Olkkola KT, Neuvonen PJ. Source: Fundamental & Clinical Pharmacology. 1996; 10(3): 314-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8836707&dopt=Abstract
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The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia. Author(s): Grace RF. Source: Anaesthesia. 2003 September; 58(9): 904-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911367&dopt=Abstract
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The effects of diazepam (valium) and aggressive disposition on human aggression: an experimental investigation. Author(s): Ben-Porath DD, Taylor SP. Source: Addictive Behaviors. 2002 March-April; 27(2): 167-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817760&dopt=Abstract
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The effects of diazepam on sensory gating in healthy volunteers. Author(s): van Luijtelaar G. Source: Neuroscience Letters. 2003 April 24; 341(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676345&dopt=Abstract
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The effects of diazepam on sleep spindles: a qualitative and quantitative analysis. Author(s): Suetsugi M, Mizuki Y, Ushijima I, Kobayashi T, Watanabe Y. Source: Neuropsychobiology. 2001 January; 43(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150899&dopt=Abstract
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The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype. Author(s): Wan J, Xia H, He N, Lu YQ, Zhou HH. Source: British Journal of Clinical Pharmacology. 1996 October; 42(4): 471-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8904619&dopt=Abstract
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The transcriptional and translational control of diazepam binding inhibitor expression in rat male germ-line cells. Author(s): Kolmer M, Pelto-Huikko M, Parvinen M, Hoog C, Alho H. Source: Dna and Cell Biology. 1997 January; 16(1): 59-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9022045&dopt=Abstract
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The use of diazepam and ketamine for i.v. conscious sedation in outpatient surgery settings. Author(s): Ringler JD. Source: Aorn Journal. 1995 October; 62(4): 638-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8787384&dopt=Abstract
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The utility of diazepam loading in the treatment of alcohol withdrawal among psychiatric inpatients. Author(s): Salloum IM, Cornelius JR, Daley DC, Thase ME. Source: Psychopharmacology Bulletin. 1995; 31(2): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7491383&dopt=Abstract
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Therapeutic trial of diazepam versus placebo in acute chloroquine intoxications of moderate gravity. Author(s): Clemessy JL, Angel G, Borron SW, Ndiaye M, Le Brun F, Julien H, Galliot M, Vicaut E, Baud FJ. Source: Intensive Care Medicine. 1996 December; 22(12): 1400-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986493&dopt=Abstract
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Time course of the effects of diazepam and lorazepam on perceptual priming and explicit memory. Author(s): Legrand F, Vidailhet P, Danion JM, Grange D, Giersch A, Van der Linden M, Imbs JL. Source: Psychopharmacology. 1995 April; 118(4): 475-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7568635&dopt=Abstract
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Time dependent influence of diazepam on the pharmacokinetics of ibuprofen in man. Author(s): Bapuji AT, Rambhau D, Srinivasu P, Rao BR, Apte SS. Source: Drug Metabol Drug Interact. 1999; 15(1): 71-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10707114&dopt=Abstract
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Tizanidine treatment of spasticity: a meta-analysis of controlled, double-blind, comparative studies with baclofen and diazepam. Author(s): Groves L, Shellenberger MK, Davis CS. Source: Adv Ther. 1998 July-August; 15(4): 241-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10186943&dopt=Abstract
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Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Lorazepam or diazepam for generalised convulsions in adults. Author(s): Butler J, Lewis M. Source: Emergency Medicine Journal : Emj. 2001 March; 18(2): 116-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300182&dopt=Abstract
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Trait anxiety and the effect of a single high dose of diazepam in unipolar depression. Author(s): Bruijn JA, Moleman P, van den Broek WW, Mulder PG. Source: Journal of Psychiatric Research. 2001 November-December; 35(6): 331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684140&dopt=Abstract
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Transient syncope and ECG changes associated with the concurrent administration of clozapine and diazepam. Author(s): Tupala E, Niskanen L, Tiihonen J. Source: The Journal of Clinical Psychiatry. 1999 September; 60(9): 619-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10520983&dopt=Abstract
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Traumatic mutism in severe head injury relieved by oral diazepam. Author(s): Caradoc-Davies TH. Source: Disability and Rehabilitation. 1996 September; 18(9): 482-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8877308&dopt=Abstract
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Treating repetitive seizures with a rectal diazepam formulation: a randomized study. The North American Diastat Study Group. Author(s): Cereghino JJ, Mitchell WG, Murphy J, Kriel RL, Rosenfeld WE, Trevathan E. Source: Neurology. 1998 November; 51(5): 1274-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818845&dopt=Abstract
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Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test. Author(s): De Negri M, Baglietto MG, Battaglia FM, Gaggero R, Pessagno A, Recanati L. Source: Brain & Development. 1995 September-October; 17(5): 330-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8579219&dopt=Abstract
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Treatment of out-of-hospital status epilepticus with diazepam rectal gel. Author(s): Fitzgerald BJ, Okos AJ, Miller JW. Source: Seizure : the Journal of the British Epilepsy Association. 2003 January; 12(1): 525. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495650&dopt=Abstract
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Treatment, discontinuation, and psychomotor effects of diazepam in women with generalized anxiety disorder. Author(s): Pourmotabbed T, Mcleod DR, Hoehn-Saric R, Hipsley P, Greenblatt DJ. Source: Journal of Clinical Psychopharmacology. 1996 June; 16(3): 202-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8784650&dopt=Abstract
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Urinary excretion of diazepam metabolites in healthy volunteers and drug users. Author(s): Smith-Kielland A, Skuterud B, Olsen KM, Morland J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2001 May; 61(3): 237-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386610&dopt=Abstract
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Use of rectal diazepam in the community. Author(s): Mackereth S. Source: Developmental Medicine and Child Neurology. 2000 November; 42(11): 785. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104353&dopt=Abstract
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Using diazepam and atropine before strabismus surgery to prevent postoperative nausea and vomiting: a randomized, controlled study. Author(s): Ozcan AA, Gunes Y, Haciyakupoglu G. Source: J Aapos. 2003 June; 7(3): 210-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825062&dopt=Abstract
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Venous sequelae following venipuncture and intravenous diazepam administration. Part One: Etiological factors. Author(s): Weir I, Holmes HI, Young ER. Source: Oral Health. 1996 May; 86(5): 9-13, 15, 17. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8948232&dopt=Abstract
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Warfarin-fluoxetine and diazepam-fluoxetine interaction. Author(s): Dent LA, Orrock MW. Source: Pharmacotherapy. 1997 January-February; 17(1): 170-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9017779&dopt=Abstract
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CHAPTER 2. NUTRITION AND DIAZEPAM Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and diazepam.
Finding Nutrition Studies on Diazepam 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 “diazepam” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “diazepam” (or a synonym): •
A comparison of thiopental, propofol, and diazepam-ketamine anesthesia for evaluation of laryngeal function in dogs premedicated with butorphanolglycopyrrolate. Author(s): Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia 65211, USA. Source: Gross, M E Dodam, J R Pope, E R Jones, B D J-Am-Anim-Hosp-Assoc. 2002 NovDecember; 38(6): 503-6 0587-2871
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A double-blind comparative study of three formulations of diazepam in volunteers. Author(s): Department of Anaesthesia, Wellington Clinical School, New Zealand. Source: Forrest, P Galletly, D C Anaesth-Intensive-Care. 1988 May; 16(2): 158-63 0310057X
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A novel method for measuring the hepatic first-pass effect and metabolic rate of L3,4-dihydroxyphenylalanine (DOPA), diazepam and inulin in rat liver. Author(s): Institute of Whole Body Metabolism, Inba, Chiba, Japan. Source: Nishigaki, J Suzuki, Y Shigematsu, A Biol-Pharm-Bull. 1998 July; 21(7): 735-40 0918-6158
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Brain lipids in rat after chronic diazepam treatment. Author(s): Institute for Medical Research, Beograd, Yugoslavia. Source: Vrbaski, S R Ristic, V I Petrovic, G T Ristic, M S J-Biochem-(Tokyo). 1989 May; 105(5): 705-7 0021-924X
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Comparison of anesthetic and cardiorespiratory effects of diazepam-butorphanolketamine, acepromazine-butorphanol-ketamine, and xylazine-butorphanol-ketamine in ferrets. Author(s): Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA. Source: Ko, J C Smith, T A Kuo, W C Nicklin, C F J-Am-Anim-Hosp-Assoc. 1998 SepOctober; 34(5): 407-16 0587-2871
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Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans. Author(s): Department of Psychiatry, Trafford General Hospital, Davyhulme, Manchester, UK. Source: Hellewell, J S Guimaraes, F S Wang, M Deakin, J F J-Psychopharmacol. 1999; 13(2): 122-7 0269-8811
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Differential effects of agents enhancing purinergic transmission upon the antielectroshock efficacy of carbamazepine, diphenylhydantoin, diazepam, phenobarbital, and valproate in mice. Author(s): Department of Pharmacology, Lublin Medical School, Poland. Source: Czuczwar, S J Szczepanik, B Wamil, A Janusz, W Kleinrok, Z J-Neural-TransmGen-Sect. 1990; 81(2): 153-66 0300-9564
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Discriminative stimulus effects of diazepam, ketamine and their mixture: ethanol substitution patterns. Author(s): Department of Psychiatry, UT Southwestern Medical Center, Dallas 752359070, USA. Source: Harrison, Y E Jenkins, J A Rocha, B A Lytle, D A Jung, M E Oglesby, M W Behav-Pharmacol. 1998 February; 9(1): 31-40 0955-8810
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Does sodium valproate increase clinical effects of diazepam? Double blind study. Author(s): Inst. Organic Chemistry and Biochemistry, Czechoslovak Acad. Sci., Prague. Source: Vinar, O Dvorak, A Vinarova, E Fackova, M Pavlicek, N Tosnerova, T Husovska, G Act-Nerv-Super-(Praha). 1989 June; 31(2): 106-7 0001-7604
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Effect of diazepam and clonazepam on the function of isolated rat platelet and neutrophil. Author(s): Department of Pharmacology and Toxicology, Lublin Medical University, Lublin, Poland. Source: Rajtar, G Zolkowska, D Kleinrok, Z Med-Sci-Monit. 2002 April; 8(4): PI37-44 1234-1010
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Effects of peripheral type benzodiazepine antagonist PK 11195 on the lipid-lowering activity of diazepam in albino rats. Author(s): Department of Pharmacology, University of Medicine and Pharmacy, ClujNapoca, Romania. Source: Cuparencu, B Horak, J Rev-Roum-Physiol. 1991 Jul-December; 28(3-4): 109-11 0035-399X
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Evaluation of sedative and cardiorespiratory effects of diazepam-butorphanol, acepromazine-butorphanol, and xylazine-butorphanol in ferrets. Author(s): Department of Large/Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA. Source: Ko, J C Villarreal, A Kuo, W C Nicklin, C F J-Am-Anim-Hosp-Assoc. 1998 MayJune; 34(3): 242-50 0587-2871
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Evidence for an involvement of the ammonia-decreasing action of L-arginine in suppressing picrotoxin-induced convulsions in rats and its additive action with diazepam. Author(s): Department of Pharmacology and Environmental Toxicology, Dr A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai, India. Source: Vanaja, P JayakuMarch, A R Neurol-Res. 2001 September; 23(6): 622-6 0161-6412
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Factors affecting diazepam availability from intravenous admixture solutions. Author(s): Intensive Care Unit, Universidade Federal do Parana, Brasil. Source: Arruda, W O Brito Filho, D Rosa, S L Fontoura, P S Cardoso, M de A ArqNeuropsiquiatr. 1989 September; 47(3): 291-4 0004-282X
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Ganglioside a/b ratio in different rat brain regions following chronic diazepam treatment. Author(s): Institute of Pathological Physiology, School of Medicine, University of Belgrade, 11000 Belgrade, Yugoslavia. Source: De Luka, S R Protic, S Vrbaski, S R Neurol-Sci. 2002 June; 23(2): 69-74 1590-1874
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Gastric emptying and intestinal transit times of radiopaque markers in cats fed a high-fiber diet with and without low-dose intravenous diazepam. Author(s): The Department of Veterinary Clinical Sciences, Massey University, Palmerston North, New Zealand. Source: Chandler, M L Guilford, W G Lawoko, C R Whittem, T Vet-Radiol-Ultrasound. 1999 Jan-February; 40(1): 3-8 1058-8183
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Inhibition of diazepam on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity. Author(s): College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea. Source: Woo, S H Kim, H S Pharmacol-Res. 2001 December; 44(6): 467-72 1043-6618
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Interactions between angiotensin II, diazepam, clonazepam and di-n-propylacetate in pentylenetetrazol kindling seizures in mice. Author(s): Department of Experimental Pharmacology, Bulgarian Academy of Science, Sofia. Source: Georgiev, V P Lazarova, M B Kambourova, T S Neuropeptides. 1991 April; 18(4): 187-91 0143-4179
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Midazolam versus diazepam in lipid emulsion as conscious sedation for colonoscopy with or without reversal of sedation with flumazenil. Author(s): Department of Medicine, University Hospital of Gasthuisberg, Leuven, Belgium. Source: Macken, E Gevers, A M Hendrickx, A Rutgeerts, P Gastrointest-Endosc. 1998 January; 47(1): 57-61 0016-5107
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Modulation of bistratified cell IPSPs and basket cell IPSPs by pentobarbitone sodium, diazepam and Zn2+: dual recordings in slices of adult rat hippocampus. Author(s): Department of Physiology, Royal Free and University College Medical School London, UK.
[email protected] Source: Pawelzik, H Bannister, A P Deuchars, J Ilia, M Thomson, A M Eur-J-Neurosci. 1999 October; 11(10): 3552-64 0953-816X
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Potentiation by saiboku-to of diazepam-induced decreases in hippocampal and striatal acetylcholine release in rats. Author(s): Kampo & Pharmacognosy Laboratories, Tsumura, Ami-machi, Inashiki-gun, Ibaraki, Japan.
[email protected] Source: Ikarashi, Y Yuzurihara, M Phytomedicine. 2002 December; 9(8): 700-8 0944-7113
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Solubilization of diazepam. Author(s): College of Pharmacy, University of Arizona, Tucson, USA. Source: Alvarez Nunez, F A Yalkowsky, S H PDA-J-Pharm-Sci-Technol. 1998 JanFebruary; 52(1): 33-6 1079-7440
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Synergistic anticonvulsant action of diazepam & clonazepam with amino-oxyacetic acid against isoniazid-induced convulsions in rats. Source: Paul, V Krishnamoorthy, M S Indian-J-Med-Res. 1989 April; 90103-6 0971-5916
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The effect of bergamottin on diazepam plasma levels and P450 enzymes in beagle dogs. Author(s): Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA.
[email protected] Source: Sahi, Jasminder Reyner, Eric L Bauman, Jonathan N Gueneva Boucheva, Kristina Burleigh, James E Thomas, V Hayden Drug-Metab-Dispos. 2002 February; 30(2): 135-40 0090-9556
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The effect of intravenous diazepam on solid phase gastric emptying in normal cats. Source: Steyn, P.F. Twedt, D. Toombs, W. Vet-radiol-ultrasound. Raleigh, NC : American College of Veterinary Radiology. Nov/December 1997. volume 38 (6) page 469-473. 1058-8183
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The pharmacokinetics of intraduodenally administered diazepam in rats as influenced by composition of the central lymph. Author(s): Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Kralove. Source: Lamka, J Jindrova, O Rudisar, L Kohoutek, P Gallova, S Kvetina, J PhysiolBohemoslovolume 1989; 38(5): 441-8 0369-9463
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to diazepam; 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 Clorazepate Dipotassium Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND DIAZEPAM Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to diazepam. 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 diazepam 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 “diazepam” (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 diazepam: •
A comparative study of diazepam and acupuncture in patients with osteoarthritis pain: a placebo controlled study. Author(s): Thomas M, Eriksson SV, Lundeberg T. Source: The American Journal of Chinese Medicine. 1991; 19(2): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1816730&dopt=Abstract
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A comparison of lorazepam and diazepam as oral premedicants for surgery under regional anaesthesia. Author(s): Magbagbeola JA. Source: British Journal of Anaesthesia. 1974 June; 46(6): 449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4156481&dopt=Abstract
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A controlled comparison of relaxation and diazepam in panic disorder. Author(s): Taylor CB, Kenigsberg ML, Robinson JM.
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Source: The Journal of Clinical Psychiatry. 1982 October; 43(10): 423-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6749827&dopt=Abstract •
Anxiolytic-like effects of kava-kava in the elevated plus maze test--a comparison with diazepam. Author(s): Rex A, Morgenstern E, Fink H. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 June; 26(5): 855-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369257&dopt=Abstract
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Artefact recognition and diazepam in electric response audiometry. Author(s): Spreng M. Source: Audiology : Official Organ of the International Society of Audiology. 1973 MayJune; 12(3): 137-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4681823&dopt=Abstract
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Automatic quantification of withdrawal from 5-day diazepam in rats: ultrasonic distress vocalizations and hyperreflexia to acoustic startle stimuli. Author(s): Miczek KA, Vivian JA. Source: Psychopharmacology. 1993; 110(3): 379-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7831436&dopt=Abstract
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Benzodiazepine receptor distribution and diazepam binding in schizophrenia: an exploratory study. Author(s): Schroder J, Bubeck B, Demisch S, Sauer H. Source: Psychiatry Research. 1997 February 7; 68(2-3): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9104759&dopt=Abstract
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Cardiac arrest caused by oral diazepam intoxication. Author(s): Berger R, Green G, Melnick A. Source: Clinical Pediatrics. 1975 September; 14(9): 842-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1157438&dopt=Abstract
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Comparative effects of diazepam and buspirone on subjective feelings, psychological tests and the EEG. Author(s): Bond AJ, Lader MH. Source: Int Pharmacopsychiatry. 1981; 16(4): 212-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6121766&dopt=Abstract
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Comparative psychotropic effects of trazodone, imipramine and diazepam in normal subjects. Author(s): Karniol IG, Dalton J, Lader M.
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Source: Curr Ther Res Clin Exp. 1976 September; 20(3): 337-48. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=822990&dopt=Abstract •
Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses. Author(s): Danjou P, Warot D, Hergueta T, Lacomblez L, Bouhours P, Puech AJ. Source: International Clinical Psychopharmacology. 1992 November; 7(2): 73-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1487624&dopt=Abstract
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Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans. Author(s): Hellewell JS, Guimaraes FS, Wang M, Deakin JF. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(2): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475716&dopt=Abstract
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Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man. Author(s): Bitsios P, Philpott A, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(3): 226-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512076&dopt=Abstract
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Contamination of urine with diazepam and mefenamic acid from an Oriental remedy. Author(s): Floren AE, Fitter W. Source: J Occup Med. 1991 November; 33(11): 1168-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1765859&dopt=Abstract
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Continuum of sedation, activation and hypnosis or hallucinosis: a comparison of low dose effects of pentobarbital, diazepam or gamma-hydroxybutyrate in the cat. Author(s): Winters WD, Kott KS. Source: Neuropharmacology. 1979 November; 18(11): 877-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=575917&dopt=Abstract
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Continuum of sedation, excitation and hypnosis induced by diazepam in the cat. Author(s): Kott K, Winters WD. Source: Proc West Pharmacol Soc. 1976; 19: 222-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=995990&dopt=Abstract
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Convulsions induced by hyperbaric oxygen: inhibition by phenobarbital, diazepam and baclofen. Author(s): Lembeck F, Beubler E.
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Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1977 March 14; 297(1): 4751. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=870832&dopt=Abstract •
Cross-substitution of diazepam for barbital results in only a low incidence of audiogenic seizures upon withdrawal in dependent rats. Author(s): Reigel CE, Bourn WM. Source: Proc West Pharmacol Soc. 1994; 37: 137-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7984646&dopt=Abstract
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Developmental alterations in maturing rats caused by chronic prenatal and postnatal diazepam treatments. Author(s): Shibuya T, Watanabe Y, Hill HF, Salafsky B. Source: Japanese Journal of Pharmacology. 1986 January; 40(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3007829&dopt=Abstract
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Diazepam effects on the cerebral responses to tonic pain: a SPET study. Author(s): Di Piero V, Ferracuti S, Sabatini U, Tombari D, Di Legge S, Pantano P, Cruccu G, Lenzi GL. Source: Psychopharmacology. 2001 November; 158(3): 252-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713614&dopt=Abstract
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Diazepam effects on the P3 event-related potential. Author(s): Ray PG, Meador KJ, Loring DW. Source: Journal of Clinical Psychopharmacology. 1992 December; 12(6): 415-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1335460&dopt=Abstract
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Diazepam enhances etoposide-induced cytotoxicity in U-87 MG human glioma cell line. Author(s): Lavicka J, Sarissky M, Mirossay A, Sulla I, Mojzis J, Mirossay L. Source: Fundamental & Clinical Pharmacology. 2001 June; 15(3): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468031&dopt=Abstract
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Diazepam hypnosis for orthipaedic manipulations. Author(s): Gunther SF, Usnr LM. Source: The Journal of Trauma. 1975 April; 15(4): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1127753&dopt=Abstract
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Diazepam receptor characterization: specific binding of a benzodiazepine to macromolecules in various areas of rat brain. Author(s): Bosmann HB, Case KR, DiStefano P.
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Source: Febs Letters. 1977 October 15; 82(2): 368-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=410665&dopt=Abstract •
Diazepam withdrawal: effects of diazepam and gepirone on acoustic startle-induced 22 kHz ultrasonic vocalizations. Author(s): Vivian JA, Farrell WJ, Sapperstein SB, Miczek KA. Source: Psychopharmacology. 1994 February; 114(1): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7846191&dopt=Abstract
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Diazepam: effect on multiple electroacupuncture-induced changes in regional GABA of mammalian central nervous system. Author(s): Chakrabarti S, Ganguly A, Poddar MK. Source: Methods Find Exp Clin Pharmacol. 1991 April; 13(3): 165-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2051841&dopt=Abstract
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Diazepam-binding inhibitor33-50 elicits Ca2+ oscillation and CCK secretion in STC-1 cells via L-type Ca2+ channels. Author(s): Yoshida H, Tsunoda Y, Owyang C. Source: The American Journal of Physiology. 1999 March; 276(3 Pt 1): G694-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070046&dopt=Abstract
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Different sensitivity of pain-related chemosensory potentials evoked by stimulation with CO2, tooth pulp event-related potentials, and acoustic event-related potentials to the tranquilizer diazepam. Author(s): Thurauf N, Ditterich W, Kobal G. Source: British Journal of Clinical Pharmacology. 1994 December; 38(6): 545-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7888293&dopt=Abstract
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Diffusion of [2-14C]diazepam across isolated hairless mouse stratum corneum/epidermal tissues. Author(s): Koch RL, Palicharla P, Groves MJ. Source: The Journal of Investigative Dermatology. 1988 March; 90(3): 317-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3126246&dopt=Abstract
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Dissociation between anxiolytic and hypomnestic effects for combined extracts of zingiber officinale and ginkgo biloba, as opposed to diazepam. Author(s): Hasenohrl RU, Topic B, Frisch C, Hacker R, Mattern CM, Huston JP. Source: Pharmacology, Biochemistry, and Behavior. 1998 February; 59(2): 527-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9477004&dopt=Abstract
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Double-blind evaluation of diazepam, sodium pentobarbital, and placebo as adjunctive premedicants prior to discography. Author(s): Feffer HL.
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Source: Clinical Orthopaedics and Related Research. 1974 May; 100(0): 242-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4599160&dopt=Abstract •
Effect of diazepam on electroacupuncture-induced changes in regional gammaaminobutyric acid of the rat central nervous system. Author(s): Chakrabarti S, Poddar MK. Source: Neuroscience Research. 1989 October; 7(1): 24-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2812569&dopt=Abstract
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Effect of diazepam, apomorphine and haloperidol on the audiogenic immobility reaction and on the open field behavior. Author(s): Hard E, Engel J, Larsson K, Musi B. Source: Psychopharmacology. 1985; 85(1): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3920692&dopt=Abstract
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Effect of electroacupuncture on the long-term diazepam-induced changes in regional GABA of mammalian central nervous system. Author(s): Chakrabarti S, Poddar MK. Source: Methods Find Exp Clin Pharmacol. 1992 March; 14(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1598023&dopt=Abstract
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Effect of melperone, chlorpromazine, haloperidol, and diazepam on experimental anxiety in normal subjects. Author(s): Molander L. Source: Psychopharmacology. 1982; 77(2): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6126901&dopt=Abstract
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Effect of midazolam and diazepam premedication on central nervous system and cardiovascular toxicity of bupivacaine in pigs. Author(s): Bernards CM, Carpenter RL, Rupp SM, Brown DL, Morse BV, Morell RC, Thompson GE. Source: Anesthesiology. 1989 February; 70(2): 318-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2913866&dopt=Abstract
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Effect of Panax ginseng and diazepam on brain 5-hydroxytryptamine and its modification by diclofenac in rat. Author(s): Bhattcharyya D, Sur TK. Source: Indian J Physiol Pharmacol. 1999 October; 43(4): 505-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10776470&dopt=Abstract
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Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. Author(s): Andreatini R, Leite JR.
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Source: European Journal of Pharmacology. 1994 August 1; 260(2-3): 233-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7988648&dopt=Abstract •
Effects of (-)-baclofen, clonazepam, and diazepam on tone exposure-induced hyperexcitability of the inferior colliculus in the rat: possible therapeutic implications for pharmacological management of tinnitus and hyperacusis. Author(s): Szczepaniak WS, Moller AR. Source: Hearing Research. 1996 August; 97(1-2): 46-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8844185&dopt=Abstract
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Effects of clonidine and diazepam on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man. Author(s): Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 23742. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769816&dopt=Abstract
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Effects of clonidine and diazepam on the acoustic startle response and on its inhibition by 'prepulses' in man. Author(s): Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Source: Journal of Psychopharmacology (Oxford, England). 1997; 11(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9097890&dopt=Abstract
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Effects of diazepam on auditory evoked potentials of rats elicited in a ten-tone paradigm. Author(s): Jongsma ML, van Rijn CM, van Schaijk WJ, Coenen AM. Source: Neuropsychobiology. 2000; 42(3): 158-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11015034&dopt=Abstract
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Effects of diazepam on dorsal root potentials induced by cortical paroxysmal activity. Author(s): Menetrey D, Decaud-Gasarabwe J, Besson JM. Source: European Journal of Pharmacology. 1973 November; 24(2): 158-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4765741&dopt=Abstract
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Effects of diazepam on fentanyl-induced epileptoid EEG activity and increase of multineuronal firing in limbic and mesencephalic brain structures. Author(s): Cervantes M, Antonio-Ocampo A, Ruelas R, Contreras-Gomez A, ChavezCarrillo I. Source: Archives of Medical Research. 1996 Winter; 27(4): 495-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8987184&dopt=Abstract
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Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-L-
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glutamine supplementation. Author(s): Muhling J, Sablotzki A, Fuchs M, Krull M, Dehne MG, Weiss S, Gonter J, Quandt D, Hempelmann G. Source: The Journal of Nutritional Biochemistry. 2001 January; 12(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179861&dopt=Abstract •
Effects of diazepam-infrasounds combination on locomotor activity and avoidance behaviour of rats. Author(s): Spyraki C, Papadopoulou Z, Zis B, Varonos D. Source: Pharmacology, Biochemistry, and Behavior. 1980 May; 12(5): 767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7393971&dopt=Abstract
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Effects of frontalis EMG biofeedback and diazepam in the treatment of tension headache. Author(s): Paiva T, Nunes JS, Moreira A, Santos J, Teixeira J, Barbosa A. Source: Headache. 1982 September; 22(5): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7141868&dopt=Abstract
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Effects of propranolol, atenolol, and chlordesmethyldiazepam on response to mental stress in patients with recent myocardial infarction. Author(s): Mazzuero G, Galdangelo F, Zotti AM, Bertolotti G, Tavazzi L. Source: Clin Cardiol. 1987 June; 10(6): 293-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2885116&dopt=Abstract
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Effects of subacutely administered saiboku-to, an oriental herbal medicine, on pharmacodynamics and pharmacokinetics of diazepam in rodents. Author(s): Yuzurihara M, Ikarashi Y, Ishihara K, Kushida H, Ishige A, Sasaki H, Maruyama Y. Source: Eur J Drug Metab Pharmacokinet. 2000 April-June; 25(2): 127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112094&dopt=Abstract
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Effects of systemic and intra-amygdaloid diazepam on long-term habituation of acoustic startle in rats. Author(s): Young BJ, Helmstetter FJ, Rabchenuk SA, Leaton RN. Source: Pharmacology, Biochemistry, and Behavior. 1991 August; 39(4): 903-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1763110&dopt=Abstract
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Effects on EMG feedback, diazepam and their combination on chronic anxiety. Author(s): Lavallee YJ, Lamontagne Y, Pinard G, Annable L, Tetrault L. Source: Journal of Psychosomatic Research. 1977; 21(1): 65-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=323471&dopt=Abstract
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Effects on memory following a single oral dose of diazepam. Author(s): Rodrigo G, Lusiardo M. Source: Psychopharmacology. 1988; 95(2): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3137608&dopt=Abstract
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Evidence for a diazepam-binding inhibitor (DBI) benzodiazepine receptor-like mechanism in ecdysteroidogenesis by the insect prothoracic gland. Author(s): Snyder MJ, Van Antwerpen R. Source: Cell and Tissue Research. 1998 October; 294(1): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9724466&dopt=Abstract
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Frequency domain source localization shows state-dependent diazepam effects in 47channel EEG. Author(s): Michel CM, Pascual-Marqui RD, Strik WK, Koenig T, Lehmann D. Source: Journal of Neural Transmission. General Section. 1995; 99(1-3): 157-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8579802&dopt=Abstract
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Gastric emptying and intestinal transit times of radiopaque markers in cats fed a high-fiber diet with and without low-dose intravenous diazepam. Author(s): Chandler ML, Guilford WG, Lawoko CR, Whittem T. Source: Vet Radiol Ultrasound. 1999 January-February; 40(1): 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10023988&dopt=Abstract
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Honokiol, a putative anxiolytic agent extracted from magnolia bark, has no diazepamlike side-effects in mice. Author(s): Kuribara H, Stavinoha WB, Maruyama Y. Source: The Journal of Pharmacy and Pharmacology. 1999 January; 51(1): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10197425&dopt=Abstract
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Hypnotic susceptibility and personality: the consequences of diazepam and the sex of the subjects. Author(s): Gibson HB, Corcoran ME, Curran JD. Source: The British Journal of Psychology. 1977 February; 68(1): 51-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=856373&dopt=Abstract
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In vitro effect of diazepam and prednisolone on leukemic cells from acute lymphoid leukemia cases. Author(s): Sasaki R, Takaku F, Miura Y. Source: Nippon Ketsueki Gakkai Zasshi. 1984 September; 47(6): 1287-92. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6595932&dopt=Abstract
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Influence of diazepam and buspirone on human heart rate and the evoked cardiac response under varying cognitive load. Author(s): Unrug A, Bener J, Barry RJ, van Luijtelaar EL, Coenen AM, Kaiser J. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 1997 February; 25(2): 177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9101342&dopt=Abstract
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Inhibition of [methyl-3H]diazepam binding to rat brain membranes in vitro by dinatin and skrofulein. Author(s): Shen XL, Nielsen M, Witt MR, Sterner O, Bergendorff O, Khayyal M. Source: Zhongguo Yao Li Xue Bao. 1994 September; 15(5): 385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7717057&dopt=Abstract
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Interaction of diazepam and naloxone on acupuncture induced pain relief. Author(s): Eriksson SV, Lundeberg T, Lundeberg S. Source: The American Journal of Chinese Medicine. 1991; 19(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1654741&dopt=Abstract
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Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica. Author(s): Ishihara K, Kushida H, Yuzurihara M, Wakui Y, Yanagisawa T, Kamei H, Ohmori S, Kitada M. Source: The Journal of Pharmacy and Pharmacology. 2000 August; 52(8): 1023-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007075&dopt=Abstract
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Interactions of Ginkgo biloba extract (EGb 761), diazepam and ethyl beta-carboline-3carboxylate on social behavior of the rat. Author(s): Chermat R, Brochet D, DeFeudis FV, Drieu K. Source: Pharmacology, Biochemistry, and Behavior. 1997 February; 56(2): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9050093&dopt=Abstract
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Intrathecal diazepam suppresses nociceptive reflexes and potentiates electroacupuncture effects in pentobarbital-anesthetized rats. Author(s): Pomeranz B, Nguyen P. Source: Neuroscience Letters. 1987 June 26; 77(3): 316-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3614765&dopt=Abstract
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Letter: Cardiac arrest with diazepam. Author(s): Sherman PM. Source: J Oral Surg. 1974 August; 32(8): 567. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4601841&dopt=Abstract
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Lorazepam and diazepam differently impair divided attention. Author(s): Jalava KM, Mattila MJ, Tarssanen M, Vanakoski J. Source: Pharmacology, Biochemistry, and Behavior. 1995 June-July; 51(2-3): 189-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7667327&dopt=Abstract
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Memory under diazepam-morphine neuroleptanesthesia in male surgical patients. Author(s): Eisenberg L, Taub HA, Burana A. Source: Anesthesia and Analgesia. 1974 July-August; 53(4): 488-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4858243&dopt=Abstract
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Pediatric premedication with diazepam or hydroxyzine: oral versus intramuscular route. Author(s): Root B, Loveland JP. Source: Anesthesia and Analgesia. 1973 September-October; 52(5): 717-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4738192&dopt=Abstract
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Phenytoin-diazepam interaction. Author(s): Murphy A, Wilbur K. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 659-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708941&dopt=Abstract
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Physostigmine reversal of diazepam-induced hypnosis. A study in human volunteers. Author(s): Avant GR, Speeg KV Jr, Freemon FR, Schenker S, Berman ML. Source: Annals of Internal Medicine. 1979 July; 91(1): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=380427&dopt=Abstract
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Potentiation by saiboku-to of diazepam-induced decreases in hippocampal and striatal acetylcholine release in rats. Author(s): Ikarashi Y, Yuzurihara M. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 December; 9(8): 700-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587689&dopt=Abstract
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Rapid arrest of seizures with an inhalation aerosol containing diazepam. Author(s): Xi LY, Zheng WM, Zhen SM, Xian NS. Source: Epilepsia. 1994 March-April; 35(2): 356-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8156957&dopt=Abstract
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Reaction time to acoustic or visual stimuli after administration of camazepam and diazepam in man. Author(s): Tallone G, Ghirardi P, Bianchi MC, Ravaccia F, Bruni G, Loreti P.
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Source: Arzneimittel-Forschung. 1980; 30(6): 1021-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6106497&dopt=Abstract •
Reduction of diazepam dose and complications by hypnosis and an opioid analgesic (a study of 409 consecutive dental patients). Author(s): Litchfield NB. Source: Dent Anaesth Sedat. 1982 April; 11(1): 5-17. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6127241&dopt=Abstract
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Reversal of diazepam withdrawal induced hyperactivity in mice by BR 16-A (Mentat), a herbal preparation. Author(s): Kulkarni SK, Sharma A. Source: Indian J Exp Biol. 1994 December; 32(12): 886-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7896322&dopt=Abstract
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Reversibility of diazepam overdose by physostigmine. Author(s): Havasi G, Gintautas J, Warren PR, Havasi I, Thomas ET, Racz GB. Source: Proc West Pharmacol Soc. 1981; 24: 109-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7255429&dopt=Abstract
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Sedation for local analgesia. Distraction and diazepam. Author(s): Scott DL. Source: Anaesthesia. 1975 July; 30(4): 471-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1147188&dopt=Abstract
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Sedative, anticonvulsant and behaviour modifying effects of Centranthus longiflorus ssp. longiflorus: a study of comparison to diazepam. Author(s): Buyukokuroglu ME, Demirezer LO, Guvenalp Z. Source: Pharmazie. 2002 August; 57(8): 559-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227198&dopt=Abstract
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Serum protein binding of phenytoin, diazepam and propranolol in age-related decrease in renal function. Author(s): Tiula E, Elfving S. Source: Ann Clin Res. 1987; 19(3): 163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3674731&dopt=Abstract
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Six weeks of diazepam treatment in normal women: effects on psychomotor performance and psychophysiology. Author(s): McLeod DR, Hoehn-Saric R, Labib AS, Greenblatt DJ.
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Source: Journal of Clinical Psychopharmacology. 1988 April; 8(2): 83-99. Erratum In: J Clin Psychopharmacol 1988 October; 8(5): 310. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3372718&dopt=Abstract •
Skin conductance responses to auditory stimuli and anticipatory responses before venepuncture in patients premedicated with diazepam or morphine. Author(s): Geddes SM, Gray WM, Millar K, Asbury AJ. Source: British Journal of Anaesthesia. 1993 October; 71(4): 512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8260299&dopt=Abstract
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Some behavioral effects of chlorodesmethyldiazepam and lorazepam. Author(s): Kostowski W, Plaznik A, Pucilowski O, Trzaskowska E, Lipinska T. Source: Pol J Pharmacol Pharm. 1981; 33(6): 597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6127668&dopt=Abstract
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Sound vibration, a non-invasive stress: antagonism by diazepam. Author(s): Eisenberg RM. Source: Psychopharmacology. 1993; 110(4): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7870918&dopt=Abstract
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Stimulation of food intake in horses by diazepam and promazine. Author(s): Brown RF, Houpt KA, Schryver HF. Source: Pharmacology, Biochemistry, and Behavior. 1976 October; 5(4): 495-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1005496&dopt=Abstract
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Suanzaorentang versus diazepam: a controlled double-blind study in anxiety. Author(s): Chen HC, Hsieh MT, Shibuya TK. Source: Int J Clin Pharmacol Ther Toxicol. 1986 December; 24(12): 646-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2880811&dopt=Abstract
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The anxiolytic action of mGlu2/3 receptor agonist, LY354740, in the fear-potentiated startle model in rats is mechanistically distinct from diazepam. Author(s): Tizzano JP, Griffey KI, Schoepp DD. Source: Pharmacology, Biochemistry, and Behavior. 2002 September; 73(2): 367-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117591&dopt=Abstract
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The CCK-B antagonist LY288513 blocks diazepam-withdrawal-induced increases in auditory startle response. Author(s): Rasmussen K, Helton DR, Berger JE, Scearce E. Source: Annals of the New York Academy of Sciences. 1994 March 23; 713: 374-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8185192&dopt=Abstract
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The CCK-B antagonist LY288513 blocks effects of diazepam withdrawal on auditory startle. Author(s): Rasmussen K, Helton DR, Berger JE, Scearce E. Source: Neuroreport. 1993 November 18; 5(2): 154-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8111002&dopt=Abstract
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The differential effects of midazolam and diazepam on intracellular Ca2+ transients and contraction in adult rat ventricular myocytes. Author(s): Kanaya N, Murray PA, Damron DS. Source: Anesthesia and Analgesia. 2002 December; 95(6): 1637-44, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456430&dopt=Abstract
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The effects of chlordesmethyldiazepam on behavioral performance and subjective judgment in normal subjects. Author(s): Zimmermann-Tansella C, Tansella M, Lader M. Source: Journal of Clinical Pharmacology. 1976 October; 16(10 Pt 1): 481-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=977791&dopt=Abstract
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The effects of diazepam on sensory gating in healthy volunteers. Author(s): van Luijtelaar G. Source: Neuroscience Letters. 2003 April 24; 341(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676345&dopt=Abstract
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The interaction of diazepam with vecuronium: a clinical study. Author(s): Yuan HB, Yang MW, Chan KH, Lee TY. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1994 October; 54(4): 259-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7982137&dopt=Abstract
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The long-term effects of diazepam and pentylenetetrazol on the potentiated startle response. Author(s): Hijzen TH, Woudenberg F, Slangen JL. Source: Pharmacology, Biochemistry, and Behavior. 1990 May; 36(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2349267&dopt=Abstract
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The use of ketamine plus diazepam anaesthesia to increase the radiosensitivity of a C3H mouse mammary adenocarcinoma in hyperbaric oxygen. Author(s): Tozer GM, Penhaligon M, Nias AH. Source: The British Journal of Radiology. 1984 January; 57(673): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6704651&dopt=Abstract
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Time dependent influence of diazepam on the pharmacokinetics of ibuprofen in man. Author(s): Bapuji AT, Rambhau D, Srinivasu P, Rao BR, Apte SS.
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Source: Drug Metabol Drug Interact. 1999; 15(1): 71-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10707114&dopt=Abstract •
Tolerance to anticonvulsant effects of clobazam, diazepam, and clonazepam in genetically epilepsy prone rats. Author(s): De Sarro GB, Rotiroti D, Gratteri S, Sinopoli S, Juliano M, De Sarro A. Source: Adv Biochem Psychopharmacol. 1992; 47: 249-54. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1354917&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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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 diazepam; 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 Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Anxiety Source: Healthnotes, Inc.; www.healthnotes.com
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Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Epilepsy Source: Healthnotes, Inc.; www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Ménière's Disease Source: Healthnotes, Inc.; www.healthnotes.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Roseola Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Vertigo Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Benzodiazepines Source: Healthnotes, Inc.; www.healthnotes.com Gaba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10027,00.html Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Illicium Alternative names: Star Anise; Illicium verum (Hook, F.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Kava Source: Prima Communications, Inc.www.personalhealthzone.com Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valerian Alternative names: Valeriana officinalis Source: Integrative Medicine Communications; www.drkoop.com Valerian Source: Prima Communications, Inc.www.personalhealthzone.com Valeriana Alternative names: Valerian; Valeriana officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valeriana Officinalis Source: Integrative Medicine Communications; www.drkoop.com Viburnum Alternative names: Cramp Bark, Highbush Cranberry; Viburnum sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Yohimbe Source: Prima Communications, Inc.www.personalhealthzone.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON DIAZEPAM Overview In this chapter, we will give you a bibliography on recent dissertations relating to diazepam. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “diazepam” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on diazepam, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Diazepam ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to diazepam. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Comparison of Progressive Relaxation, Diazepam, and Placebo Drug in the Reduction of Anxiety, and As Adjuncts in the Treatment of Small Animal Phobics by Flooding by John, Rodney; Phd from Concordia University (canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK49629
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Diazepam Tolerance Effects on Vestibular Function Tests Following Repeated Oral Doses by Blau, Patricia Anne; Phd from The University of Texas at Dallas, 2002, 136 pages http://wwwlib.umi.com/dissertations/fullcit/3076661
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Effects on Human Saccadic Eye Movements of Diazepam, Pentobarbital and Dextroamphetamine by Frecker, Richard C; Phd from University of Toronto (canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK22748
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Executive Functions, Diazepam and Aggression by Pickle, Jody Lynn; Phd from Kent State University, 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3068691
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Reinforcing Properties of Diazepam under Anxiogenic Conditions in Individuals with Social Anxiety by Helmus, Todd Christian; Phd from Wayne State University, 2002, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3071790
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The Effect of Insulin, Blood Glucose Levels and Diazepam Following Transient Forebrain Ischemia in the Rat by Voll, Christopher Laurence; Phd from University of Calgary (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54346
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The Effects of Diazepam on Decision Processes and Memory Access by Coambs, Robert B; Phd from University of Toronto (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39779
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON DIAZEPAM 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 “diazepam” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on diazepam, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Diazepam By performing a patent search focusing on diazepam, 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 diazepam: •
Analgesic, anti-inflammatory and skeletal muscle relaxant compositions Inventor(s): Niazi; Sarfaraz K. (20 Riverside Dr., Deerfield, IL 60015) Assignee(s): none reported Patent Number: 6,235,314 Date filed: August 8, 2000 Abstract: Disclosed is a local skeletal muscle relaxant and a non-steroidal antiinflammatory drug in a topical composition for topical application to a patient for relief of pain. More particularly and in its preferred form, the invention involves a combination of diazepam and diclofenac in a composition for topical application to the skin of a patient as a colorless transparent gel. Excerpt(s): The present invention relates generally to a novel pharmaceutical composition matter comprising a non-steroidal anti-inflammatory drug (NSAID) in combination with a skeletal muscle relaxant, and more particularly to a topical ointment comprising a mixture of diazepam and an NSAID. The oral ingestion of certain medications such as NSAIDs and diazepam (Valium.RTM.) is well known. The analgesic and anti-inflammatory properties of NSAIDs are also well known, as is the use of diazepam to treat symptoms of acute alcohol withdrawals, control epilepsy and to relieve muscle spasms as well as short term relief of mild to moderate anxiety. Further, studies have investigated the effectiveness of the transdermal delivery of diazepam and NSAIDs individually. It would appear that the effectiveness of the transdermal delivery depends largely on the vehicle for delivery of the drug, emulsions appearing more effective than creams. It is therefore an object of the subject invention to provide a topical composition for relief of pain in an affected body part. Web site: http://www.delphion.com/details?pn=US06235314__
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Anesthetic and sedative composition Inventor(s): Burnap; Raymond W. (1528 Canada Blvd., Glendale, CA 91208) Assignee(s): none reported Patent Number: 4,017,619 Date filed: September 29, 1975 Abstract: An anesthetic and sedative composition comprising a mixture of ketamine hydrochloride and diazepam is disclosed. The ratio of ketamine hydrochloride to diazepam is 10:1. As administered in anesthetic or sedative doses patients exhibit no deleterious reduction in respiration, blood pressure or heart action and patients are unable to recall any unpleasant psychological experiences associated with the administration of the composition. Excerpt(s): This invention relates to an anesthetic and sedative composition. Many compositions are available for sedating patients or, in larger dosages, for inducing surgical anethesia in patients. These materials are used above or in combination with other agents, such as nitrous oxide, to induce narcosis and to raise the patients pain threshold so that the patient can withstand surgical procedures. Likewise in smaller
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doses, these materials can reduce anxiety and generally sedate the patient. For example the following compounds are in general use as sedative and anesthetic agents: thiopental sodium, 5-allyl-1-methyl-5-(1-methyl-2-pentynyl) barbituric acid sodium salt (brevitol), 2-bromo-2-chloro-1,1,1-trifloroethane (halothane), and the like. Most anesthetic and sedative agents, in addition to their beneficial effects, also lower certain body functions, such as respiration, blood pressure and heart action. Lowered body functions may sometimes lead to complications, particularly in older patients and in patients suffering from cardiac and vascular diseases and diseases of the kidneys and liver. Likewise, reduction in blood pressure may also lead to circulatory insufficiency during the surgical procedures which, unless alleviated, may do serious harm even to patients who have previously exhibited no signs of heart, kidney or liver disfunction. Web site: http://www.delphion.com/details?pn=US04017619__ •
Antiinflammatory compositions and methods Inventor(s): Crawford; Thomas C. (Ledyard, CT), Keely; Stanley L. (Ledyard, CT), Larson; David L. (East Lyme, CT), Lombardino; Joseph G. (Niantic, CT), Maciejko; James J. (Mystic, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 4,579,846 Date filed: January 28, 1985 Abstract: An improved antiinflammatory composition and method of treating inflammation which employs a combination of antiinflammatory piroxicam, or a pharmaceutically acceptable salt thereof, with analgesic acetaminophen, antidepressant doxepin, bronchodilator pirbuterol, minor tranquilizer diazepam, or antihypertensive trimazosin. Excerpt(s): The present invention is concerned with an improved antiinflammatory composition and method of treating inflammation which employs antiinflammatory piroxicam, or a pharmaceutically acceptable salt thereof (particularly the ethanolamine salt) in combination with analgesic acetaminophen, antidepressant doxepin, bronchodilator pirbuterol, minor tranquilizer diazepam, or antihypertensive trimazosin or a related compound. The generic names used here and elsewhere herein are from the USAN and the USP Dictionary of Drug Names, 1961-1981, Griffiths et al., ed., U.S. Pharmacopeial Convention Inc., Rockville, Md., 1984, have subsequently been assigned and published as official USAN names, and/or appear in the Merck Index 10th Edition. Gastrointestinal irritation, including ulcers, is a side effect commonly associated, to one degree or another, with antiinflammatory agents. In many cases, individuals requiring such antiinflammatory treatment are precluded from enjoying the benefits thereof because of their susceptibility to such side effects. The present combination of piroxicam with one or another of the medicinal agents defined above permits desirable antiinflammatory therapy while preventing or ameliorating said gastrointestinal irritation or ulcers. Acetaminophen has been previously reported to reduce the ulcerogenicity of aspirin [Sugers et al., J. Pharm. Pharmacol. 30, 84 (1978); ibid. 31, 840 (1979); and Adv. Prost. Thromb. Res. 8, 1547 (1980)], or of acidifed aspirin [Konturek et al., Gut 23, 536 (1982)]. However, indomethacin reversed the protective effect of acetaminophen when given with acidified aspirin (loc. cit.). In later studies, it was reported that acetaminophen reduced the ulcerogenicity of indomethacin and aspirin, but not of phenylbutazone or glafenine, and of ibuprofen only at the highest dose (800 mg/kg) of the latter compound [van Kolfschoten et al., Agents Actions 12, 247 (1982);
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Toxicology Applied Pharm. 69, 37 (1983)]. Acetaminophen in combination with ketoprofen and other particular antiinflammatory agents has been reported to provide an analgesic effect which is greater than a simple additive effect (U.S. Pat. Nos. 4,233,313 to 4,233,317; 4,234,601; 4,207,340; and 4,242,353). While we are aware of no literature reports concerning the combination of acetaminophen with piroxicam or any other oxicam for any purpose, we have been advised that a piroxicam-acetaminophen combination has been recently marketed in Argentina. Web site: http://www.delphion.com/details?pn=US04579846__ •
Benzodiazepine radioimmunoassay using I125-label Inventor(s): Davis; Raymond Vincent (North Caldwell, NJ), Fryer; Rodney Ian (North Caldwell, NJ) Assignee(s): Hoffmann-La Roche, Inc. (Nutley, NJ) Patent Number: 4,083,948 Date filed: April 4, 1977 Abstract: An improved radioimmunoassay for benzodiazepines such as diazepam, chlordiazepoxide, oxazepam, demoxepam and metabolites thereof is disclosed. Such immunoassay employs novel.sup.125 I-labelled 4'-hydroxy derivatives of these compounds as tracer. Excerpt(s): The development of immunoassy provides a powerful method for the measurement of drug levels in biological fluids. The extensive clinical use and continued development of benzodiazepines as a class of drugs makes it desirable that immunoassays be developed for these compounds. Several such immunoassays directed to benzodiazepines have been developed and reported in the literature. Thus Peskar and Spector described a radioimmunoassay procedure useful in detecting nanogram amounts of diazepam or N-desmethyldiazepam in plasma samples in J. Pharmacol. Exp. Ther. 186, 167 (1973). This assay utilized.sup.14 C-diazepam as the tracer. Antibodies were elicited using either 5- [3-(4-aminophenylazo)-4-hydroxyphenyl] -7-chloro-1,3dihydro-1-methyl-2H-1,4-benzodiazepin-2-one or 7-amino-5-(2-chlorophenyl)-3H-1,4benzodiazepin-2-(1H)-one as haptens which were subsequently coupled to bovine serum albumin (BSA) to form the desired immunogens. Subsequently, Dixon et al. reported in J. Pharm. Sci. 64, 937 (1975) of a radioimmunoassay for chlordiazepoxide in plasma. Once again the tracer compound was a.sup.14 C-labelled compound. The immunogen was derived by coupling the reactive acyl azide of 7-chloro-5(4hydrazinocarbonylmethoxyphenyl)-2-methylamino-3H-1,4-benzodia zepine 4-oxide to BSA. Web site: http://www.delphion.com/details?pn=US04083948__
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Brain derivable polypeptide factors and antibodies thereto Inventor(s): Marquardt; Hans (Mercer Island, WA), Shoyab; Mohammed (Seattle, WA), Todaro; George J. (Seattle, WA) Assignee(s): Oncogen () Patent Number: 4,963,485 Date filed: January 27, 1986
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Abstract: Novel polypeptides, polynucleotide sequences, DNA constructs and compositions are provided for the preparation and use of polypeptides associated with naturally occurring polypeptides found in brains. The low molecular weight polypeptides either are growth inhibitors for neoplastic cells without inhibiting normal cells or affect GABA-ergic transmission. The polypeptides find use in inhibiting neoplastic growth, modulating diazepam receptor response, and detecting receptors for the polypeptides. Antibodies are provided in conjunction with the polypeptides, which may be used together or separately for detecting the presence of the polypeptides. Excerpt(s): Cellular growth and differentiation appear to be initiated, promoted, maintained and regulated by a multiplicity of stimulatory, inhibitory and synergistic hormones and factors. The alteration and/or breakdown of the cellular homeostasis mechanism seems to be a basic cause of growth related diseases including neoplasia. There is a considerable interest in the isolation, characterization and mechanism of action of growth modulatory factors (stimulators and inhibitors) because of their potential use in the diaqnosis, prognosis and therapy of various diseases, such as cancer, as well as in understanding the basic mechanisms of mitosis, particularly as it may affect cancer. Besides growth and differentiation, many bodily responses are regulated by proteins, where the proteins may serve as ligands or receptors. Further investigation of the regulation of brain function and response to external and internal stimuli has resulted in the isolation of a myriad of compounds which are involved in the regulation of responses to such stimuli as pain, mood, or the like. Benzodiazepines (BZD), commonly used as anxiolytics, anticonvulsants, muscle-relaxants and sedatives, are believed to exert their pharmacological effects based on the potentiation of the.gamma.aminobutyric acid (GABA)-mediated inhibitory neurotransmission. The first step in the modulation of GABA-ergic transmission by BZD appears to be binding to specific high affinity and saturable binding sites in &.he central nervous system, where the binding sites are believed to be a component of a "supramolecular complex." The need to understand this system, as well as being able to modulate or control the system is dependent on knowing the naturally occurring ligand and the manner in which it functions. Web site: http://www.delphion.com/details?pn=US04963485__ •
Central cholecystokinin antagonists having pharmaceutical activity Inventor(s): Horwell; David C. (Foxton, GB2), Hughes; John (Swaffman Prior, GB2), Woodruff; Geoff N. (Dassels, GB2) Assignee(s): Merck Sharp and Dohme Limited (Hoddesdon, GB2) Patent Number: 5,550,126 Date filed: January 30, 1995 Abstract: Pharmaceutical compositions and methods of using CCK-ligands D,Lglutamic acid and D,L-aspartic acid as antipsychotic, antianxiety, and agents useful in treatment or prevention of withdrawal symptoms caused by withdrawal of chronic or long term use of diazepam, alcohol, cocaine or nicotine and antianxiety agents are described. Excerpt(s): Agents acting at central cholecystokinin (CCK) receptors induce satiety (Schick, Yaksh and Go, Regulatory Peptides 14:277-291, 1986. They are also expected to act as anlagesics (Hill, Hughes and Pittaway, Neuropharmacology 26:289-300, 1987, and as anticonvulsants (MacVicar, Kerrin and Davison, Brain Research, 406:130-135, 1987.
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Reduced levels of CCK-peptides have been found in the brains of schizophrenic patients compared with controls (Roberts, Ferrier, Lee, Crow, Johnstone, Owens, BacareseHamilton, McGregor, O'Shaughnessey, Polak and Bloom. Brain Research 288, 199-211, 1983). It has been proposed that changes in the activity of CCK neurones projecting to the nucleus accumbens may play a role in schizophrenic processes by influencing dopaminergic function (Totterdell and Smith, Neuroscience 19, 181-192, 1986). This is consistent with numerous reports that CCK peptides modulate dopaminergic function in the basal ganglia and particularly the nucleus accumbens (Weiss, Tanzer, and Ettenberg, Pharmacology, Biochemistry and Behaviour 30, 309-317, 1988; Schneider, Allpert and Iverson, Peptides 4, 749-753, 1983). It may therefore be expected that agents modifying CCK receptor activity may have therapeutic value in conditions associated with disturbed function of central dopaminergic function such as schizophrenia and Parkinson's disease. The cholecystokinin peptides are widely distributed in various organs of the body including the gastrointestinal tract, endocrine glands, and the nerves of the peripheral and central nervous systems. Various biologically active forms have been identified including a 33-amino acid hormone and various carboxy-terminus fragments of this peptide (e.g., the octapeptide CCK26-33 and the tetrapeptide CCK3033). (G. J. Dockray, Br. Med. Bull., 38 (No. 3):253-258, 1982). Web site: http://www.delphion.com/details?pn=US05550126__ •
Cholecystokinin antagonists, their preparation and therapeutic use Inventor(s): Holmes; Ann (Dexter, MI), Horwell; David C. (Cambridge, GB2), Kleinschroth; Jurgen (Denzlingen, DE), Padia; Janak K. (Ann Arbor, MI), Rees; David C. (Cambridge, GB2), Richardson; Reginald S. (Haverhill, GB2), Roark; William H. (Ann Arbor, MI), Roberts; Edward (Wood Ditton, GB2), Roth; Bruce D. (Ann Arbor, MI), Trivedi; Bharat K. (Farmington Hills, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 5,593,967 Date filed: April 1, 1993 Abstract: Novel cholecystokinin antagonists useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with use of nicotine, diazepam, alcohol, cocaine, coffee, or opioids. The compounds of the invention are also useful in treating and/or preventing panic. Also disclosed are pharmaceutical compositions and methods of treatment using the antagonists as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds in diagnostic compositions. Excerpt(s): Agents acting at central cholecystokinin (CCK) receptors may induce satiety (Schick, Yaksh, and Go, Regulatory Peptides 14:277-291, 1986). They are also expected to act as analgesics (Hill, Hughes, and Pittaway, Neuropharmacology 26:289-300, 1987), and as anticonvulsants (MacVicar, Kerrin, and Davison, Brain Research 406:130-135, 1987). Reduced levels of CCK-peptides have been found in the brains of schizophrenic patients compared with controls (Roberts, Ferrier, Lee, Crow, Johnstone, Owens, Bacarese-Hamilton, McGregor, O'Shaughnessey, Polak, and Bloom, Brain Research 288:199-211, 1983). It has been proposed that changes in the activity of CCK neurones projecting to the nucleus accumbens may play a role in schizophrenic processes by
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influencing dopaminergic function (Totterdell and Smith, Neuroscience 19:181-192, 1986). This is consistent with numerous reports that CCK peptides modulate dopaminergic function in the basal ganglia and particularly the nucleus accumbens (Weiss, Tanzer, and Ettenberg, Pharmacology, Biochemistry and Behaviour 30:309-317, 1988; Schneider, Allpert, and Iversen, Peptides 4:749-753, 1983). It may therefore be expected that agents modifying CCK receptor activity may have therapeutic value in conditions associated with disturbed function of central dopaminergic function such as schizophrenia and Parkinson's disease. The CCK peptides are widely distributed in various organs of the body including the gastrointestinal tract, endocrine glands, and the nerves of the peripheral and central nervous systems. Various biologically active forms have been identified including a 33-amino acid hormone and various carboxylterminus fragments of this peptide (e.g., the octapeptide CCK26-33 and the tetrapeptide CCK30-33). (G. J. Dockray, Br. Med. Bull. 38(3):253-258, 1982). Web site: http://www.delphion.com/details?pn=US05593967__ •
Combination of.beta.-adrenoceptor antagonists and anxiolytic agents Inventor(s): Voith; Katherine (Dorval, CA) Assignee(s): Ayerst, McKenna & Harrison, Inc. (Montreal, CA) Patent Number: 4,468,391 Date filed: June 25, 1982 Abstract: A.beta.-adrenoceptor antagonist, which does not penetrate or penetrates poorly the brain, is combined with subtherapeutic doses of an anxiolytic agent, such as diazepam, to give a method, and pharmaceutical or veterinary composition, for treating anxiety, stress or aggressivity without deleterious side effects associated with the central nervous system. Excerpt(s): This invention concerns a method for treating pathological states of anxiety, stress and aggressivity, and to a pharmaceutical or veterinary composition therefor. The active principle for the method and composition is an improved combination of a.beta.adrenoceptor (.beta.-AA) with an anxiolytic agent, which provides an enhanced therapeutic effect without enhancing side effects. Side effects, associated with the central nervous system (CNS), are often encountered by patients receiving one of the presently available anxiolytic agents such as diazepam and meprobamate. Sedation and impairment of motoricity are among the most serious side effects of this type. Consequently, these drugs must be used with caution by patients having activities requiring close attention or by operators of complex machinery. I have found that by combining an anxiolytic agent with a.beta.-AA which does not penetrate or penetrates poorly the central nervous system, it is possible to provide a treatment for anxiety which is more complete than that which would be expected by the mere addition of effects and, simultaneously and unexpectedly, avoids the above noted side effects of the presently available regimens. Web site: http://www.delphion.com/details?pn=US04468391__
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Diazepam enzyme conjugates Inventor(s): Rubenstein; Kenneth E. (Menlo Park, CA), Ullman; Edwin F. (Atherton, CA) Assignee(s): Syva Company (Palo Alto, CA) Patent Number: 4,046,636 Date filed: May 24, 1976 Abstract: Novel compositions are provided for the determination of one or a group of organic materials (hereinafter referred to as "ligands"), where the compositions have a ligand or ligand counterfeit bonded to an enzyme, the conjugate referred to as "enzymebound-ligand." Specifically, the ligands are benzdiazocycloheptane drugs, which are conjugated to an enzyme, so that upon binding of a receptor, usually an antibody, the activity of the enzyme changes. Determinations of the benzdiazocycloheptane drugs in a physiological fluid are performed by combining the enzyme conjugate, the physiological fluid and receptor under conditions whereby the amount of receptor bound to the conjugate is related to the amount of the benzdiazocycloheptane drug present in the sample. By metering the enzyme activity of the assay mixture and comparing the result to known standards, the amount of benzdiazocycloheptane drug present in the sample may be determined. Excerpt(s): There is a continually pressing need for rapid, accurate qualitative and quantitative determinations of biologically active substances at extremely low concentrations. The purpose of the determination can be extremely varied. Today, there is a wide need for determining the presence of drugs or narcotics in body fluids, such as saliva, blood or urine. In addition, in medical diagnosis, it is frequently important to know the presence of various substances which are synthesized naturally by the body or ingested. These include hormones, both steroidal and polypeptides, prostaglandins, toxins, as well as other materials which may be involved in body functions. Frequently, one is concerned with extremely small amounts and occasionally, with very small differences in concentrations. To meet these needs, a number of ways have been devised for analyzing for trace amounts of materials. A common method is to use thin layer chromatography (TLC). By determining the flow factors and using specific reagents, the presence of certain materials can be detected; in many instances, the particular material can be isolated and identified quantitatively, for example, by mass spectroscopy or gas phase chromatography. However, thin layer chromatography has a number of deficiencies in being slow, requiring a high degree of proficiency in its being carried out, being subject to a wide range of interfering materials, and suffering from severe fluctuations in reliability. Therefore, the absence of satisfactory alternatives has resulted in intensive research efforts to determine improved methods of separation and identification. An alternative to thin layer chromatography has been radioimmunoassay. Here, antibodies are employed for specific haptens or antigens. A radioactive analog employing a radioactive atom of high flux is used and bound to the antigen. By mixing an antibody with solutions of the hapten or antigen and the radioactive hapten or antigen analog, the radioactive analog will be prevented from binding to the antibody in an amount directly related to the concentration of the hapten or antigen in the solution. By then separating the free radioactive analog from the antibody bound radioactive analog and determining the radioactivity of the separate components, one can determine the amount of hapten or antigen in the original solution. Web site: http://www.delphion.com/details?pn=US04046636__
Patents 107
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Drug therapy for alcohol abusers Inventor(s): Radecki; Thomas E. (1600 Lincoln, Decatur, IL 62521) Assignee(s): none reported Patent Number: 5,140,032 Date filed: October 1, 1990 Abstract: A novel composition and/or method for the treatment of alcoholism, wherein the composition comprises a therapeutically effective dosage of disulfiram and a drug that affects the neurological system in a manner similar to alcohol, preferably a habitforming or addictive drug. The method comprises administering a composition to alcoholics that combines therapeutically effective dosages of disulfiram and a habitforming or addictive drug into a single composition. Preferably, the habit-forming or addictive medication is an anti-anxiety drug and is a member of the benzodiazepine family. Most preferably, the habit-forming, anti-anxiety drug is diazepam. Excerpt(s): The present invention relates to a method and composition for the treatment of alcoholism. More specifically, the present invention relates to a method that utilizes a composition comprised of two medications to treat alcohol abuse and improve patient compliance with treatment programs. The typical treatment of alcoholism has sometimes involved the use of drug therapy. Disulfiram, also known as Antabuse, has been widely used since the early 1950's in the treatment of alcoholism. Disulfiram causes a strong adverse reaction in a person within five to fifteen minutes after the person has consumed alcohol. Side-effects are believed to be minimal, and life-threatening reactions with or without alcohol are very rare. Unfortunately, disulfiram therapy has resulted in only modest success in treating alcoholism. In a recent large scale, multi-center study by the Veterans Administration (VA), the one-year abstinence rate for patients on disulfiram (18%) was no better than for the control group (20%), but disulfiram patients had significantly more days of sobriety. Typically, patients cease taking the disulfiram and discontinue treatment, resulting in a relapse in alcohol abuse. One drug that is commonly used for alcohol detoxification, but not for therapy, is diazepam, a member of the benzodiazepine family of somewhat habit-forming, anti-anxiety medications. Diazepam appears to decrease cravings for alcohol. A significant disadvantage, however, with using diazepam is that alcoholics, after only a short period of time, frequently relapse into drinking while continuing to take diazepam. Further treatment of the alcohol abuse is subsequently discontinued. Web site: http://www.delphion.com/details?pn=US05140032__
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Human DBI/ACBP-like protein Inventor(s): Au-Young; Janice (Berkeley, CA), Goli; Surya K. (Sunnyvale, CA), Hillman; Jennifer L. (San Jose, CA) Assignee(s): Incyte Pharmaceuticals, Inc. (Palo Alto, CA) Patent Number: 5,734,038 Date filed: August 16, 1996 Abstract: The present invention provides polynucleotides which identify and encode a novel human Diazepam binding inhibitor/acyl-CoA binding protein (DBI/ACBP)-like protein (DBIH). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding DBIH. The invention also
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provides for the use of substantially purified DBIH for drug delivery as well as for the production of recombinant proteins for the treatment of diseases associated with the expression of DBIH. Additionally, the invention provides for the use of antisense molecules to DBIH in the treatment of diseases associated with the expression of DBIH. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotides which hybridize with naturally occurring sequences encoding DBIH and antibodies which specifically bind to the protein. Excerpt(s): The present invention relates to nucleic acid and amino acid sequences of a novel human DBI/ACBP-like protein and to the use of these sequences in the diagnosis, study, prevention and treatment of disease. Diazepam binding inhibitor/acyl-CoA binding protein (DBI/ACBP)-like protein is a 10 kdal protein found in species ranging from yeast to mammals. It is expressed in a variety of organs and tissues. Originally, DBI was purified from rat brain based on its ability to displace diazepam from type A gamma-aminobutyrate (GABA.sub.A) receptors (Guidotti et al (1983) Proc Nat Acad Sci U.S.A. 80:3531-3535). An acyl-Coenzyme A (acyl-CoA) binding protein (ACBP) subsequently purified from liver was found to be identical to DBI (Mikkelsen J. et al (1987) Biochem J 245:857-861). The protein was known as endozepine, DBI, or ACBP, but it is now generally referred to as DBI/ACBP. DBI/ACBP, and polypeptides derived from it, have been implicated in multiple biological processes, such as 1) GABA.sub.A /benzodiazepam receptor modulation, 2) acyl-CoA metabolism, 3) steroidogenesis, and 4)insulin secretion (reviewed in Knudsen J. et al (1993) Mol Cell Biochem 123:129-138). The three-dimensional solution structure of bovine DBI/ACBP with and without bound acyl-CoA ligands has been solved by NMR (Andersen K. V. and Poulsen F. M. (1992) J Mol Biol 226:1131-41; Kragelund et al (1993) J Mol Biol 230:1260-1277). DBI/ACBP consists of four alpha helices (A1 through A4) arranged in a left-handed anti-parallel bundle, with parallel helices A1 and A4 anti-parallel to helices A2 and A3. Helix A2 interacts with each of the other three helices in a structure reminiscent of a bowl. The inner surface of the bowl has a patch of non-polar and uncharged residues at the interface between helices A2 and A3. The rims of the bowl have mainly polar and charged groups which are contributed by the hydrophilic residues of the amphipathic helices. The ligand binding site is located on the inner surface of the bowl, and it binds the aliphatic acyl chain of the fatty acyl-CoA ligand in a non-polar arrangement created partly by the protein and partly by the pantetheine and the adenosine-3'-phosphate of CoA. The pantetheine and CoA moieties likewise form a highly polar and charged surface, so that the surface together with the polar and charged rims of the protein bowl ensure the solubility of the entire complex (Kragelund et al, supra). Web site: http://www.delphion.com/details?pn=US05734038__ •
Immunoassay for N-desmethyldiazepam Inventor(s): Dixon; William R. (Dumont, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,191,738 Date filed: April 7, 1978 Abstract: Highly specific antibodies to N-desmethyldiazepam are obtained by using as an immunogen 4'-hydrazinocarbonylmethoxy-N-desmethyldiazepam coupled to an immunogenic carrier material such as bovine serum albumin. These antibodies can be employed in immunoassays for N-desmethyldiazepam which is a major metabolite of three important psychoactive drugs diazepam, chlordiazepoxide and clorazepate.
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Excerpt(s): U.S. Pat. No. 4,046,636 disclosed enzyme conjugates of benzodiazepines useful in a homogeneous enzyme immunoassay for benzodiazepines such as oxazepam, and diazepam and chloridazepoxide. In Example 8 of this patent there is disclosed the preparation of a conjugate from N-desmethyldiazepam and bovine gamma globulin through a 3'-carboxypropyl linking group attached to the 1-position of the benzodiazepine nucleus. This material is used as an immunogen to elicit antibodies which cross-react strongly with oxazepam, diazepam and chlordiazepoxide, as well as the metabolite N-desmethyldiazepam. U.S. Pat. Application Ser. No. 784,101 filed Apr. 4, 1977 discloses a radioimmunoassay for benzodiazepines such as diazepam, chlordiazepoxide, oxazepam, and metabolites thereof. The assay employs both known and novel antibodies. Novel antibodies are elicited using the diazonium salt of the 5-(4aminophenyl)benzodiazepine hapten coupled to the immunogenic carrier material as the immunogen. The radioligands employed in this assay are novel.sup.125 I-labelled 4'hydroxy derivatives of the compounds to be detected. Peskar and Spector described a radioimmunoassay procedure useful in detecting nanogram amounts of diazepam or Ndesmethyldiazepam in plasma samples in J. Pharmacol Exp. Ther. 186, 167 (1973). This assay utilized.sup.14 C-diazepam as the tracer. Antibodies were elicited using either 5[3-(4-aminophenylazo)-4-hydroxy-phenyl]-7-chloro-1,3-dihydro-1-methyl-2H -1,4benzodiazepin-2-one or 7-amino-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one as haptens which were subsequently coupled to bovine serum albumin (BSA) to form the desired immunogens. Web site: http://www.delphion.com/details?pn=US04191738__ •
Ketazocine anesthetic method of use Inventor(s): Farah; Alfred E. (Schodack, NY) Assignee(s): Sterling Drug Inc. (New York, NY) Patent Number: 4,217,354 Date filed: February 12, 1979 Abstract: The method of producing anesthesia in a mammal comprising administering intravenously to the mammal an anesthetically effective amount of a pharmaceutically acceptable salt of racemic ketazocine or levo-ketazocine with or without diazepam premedication and the method of producing analgesia in a human which comprises administering intramuscularly to the human an anesthetically effective amount of at least 1 mg. of a pharmaceutically acceptable salt of racemic ketazocine or levoketazocine are disclosed. Excerpt(s): This invention relates to a method of producing anesthesia in a mammal using ketazocine. The general anesthetics are classified as inhalation anesthetics and intravenous anesthetics (ibid., chap. 18, pp. 285-299). Adjuncts to anesthesia, which are not themselves anesthetics, (ibid., chap. 19, pp. 300-324) including diazepam (ibid., p. 302) are frequently used with the general anesthetics. The commonly used intravenous anesthetics are the barbiturates, for example, thiopental sodium, and a nonbarbiturate, ketamine hydrochloride, which are seldom used alone but are generally used in combination with the inhalation anesthetics. Moreover, the barbiturates have little if any analgesic activity and ketamine hydrochloride has undesirable cerebrospinal fluid pressor, central nervous system excitatory, and hallucinatory and other psychic effects. There is therefore a need for an intravenous anesthetic which is self-sufficient as an anesthetic, which has good analgesic properties unlike the barbiturates and which does not have the undesirable effects of ketamine hydrochloride. In a method aspect the
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invention is the method of producing anesthesia in a mammal which comprises administering intravenously to the mammal an anesthetically effective amount of a pharmaceutically acceptable salt of racemic ketazocine or levoketazocine. Web site: http://www.delphion.com/details?pn=US04217354__ •
Method and system for administering a dissociative, unconscious type of anesthesia Inventor(s): Hamacher; Edward N. (Ste. 660, Southcenter Medical Bldg., West 105, 8th Ave., Spokane, WA) Assignee(s): none reported Patent Number: 4,246,894 Date filed: May 24, 1979 Abstract: A method and system of administering a dissociative unconscious type of anesthesia are disclosed. The method and system are designed for use in office surgical units and outpatient facilities. Administration by a nurse or a physician without anesthesia training can be done with minimum danger to the patient and minimum recovery time. The method and system utilizes the intravenous titration method of administration of a combination of drugs by which the patient is placed in a dissociative, unconscious state and maintained in this state until completion of the procedure, at which time the effect of the drugs is reversed by other drugs as desired. The intravenous anesthesia is supported by infiltration of a local anesthetic, such as Xylocaine. The combination of drugs include the basal hypnotic diazepam (Valium), a dissociated unconsciousness and general analgesia phencyclidine (Ketamine) and the narcotic analgesic Nisentil. The effects of the anesthetic can be reversed by the person administering the anesthesia as soon as their desired purpose has been accomplished. Excerpt(s): This invention relates to an anesthesia method and system for inducing a dissociative, unconscious state of anesthesia in patients. Most surgical procedures today, including those carried out in office surgical units or outpatient facilities make use of the traditional anesthetics such as sodium pentathol and/or barbiturates. Many patients react adversely to the administration of sodium pentathol and during recovery become extremely nauseated. This not only causes distress to the patient but can create postoperative complications adversely affecting the patient. This is particularly true in plastic, reconstructive and cosmetic surgery where delicate portions of the facial muscles and bone structure are involved. Another problem with conventional anesthetic procedures in general use is that they must be administered by a trained anethesiologist. This makes the medical procedure decidedly more expensive to the patient. What has been needed, but not available, is an anesthesia system which is sufficiently safe that it can be administered in an office or outpatient clinic by a nurse or physician without anesthesia training. Also, what has been needed is an anesthetic system where the patient can be given commands and respond during the surgical procedure and where, once the patient recovers, only slight effects of nausea are encountered. Web site: http://www.delphion.com/details?pn=US04246894__
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Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (GABA) agonists Inventor(s): Ruiz; Guadalupe (Corona, CA), WoldeMussie; Elizabeth (Laguna Niguel, CA) Assignee(s): Allergan Sales, Inc. (Irvine, CA) Patent Number: 6,077,839 Date filed: March 19, 1992 Abstract: Ophthalmic compositions and a method are disclosed for treating glaucoma and/or ocular hypertension in the mammalian eye by topically administering to the mammalian eye the ophthalmic composition of the invention which contains as the active ingredient one or more gamma aminobutyric acid agonist compounds. Examples of gamma aminobutyric acid agonists utilized in the ophthalmic composition and method of treatment are: gamma aminobutyric acid (GABA), 5-(aminomethyl)-3(2H)isoxazolone (muscimol), 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and a pharmaceutically acceptable salt of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, piperidine-4-sulfonic acid and a pharmaceutically acceptable salt of piperidine-4sulfonic acid, 3-(2H)-isothiazolone, 5-(aminomethyl) (thiomuscimol), 7-chloro-1,3dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (diazepam), 7-chloro-1-[2(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-b enzodiazaepin-2-one (flurazepam) and a pharmaceutically acceptable salt of 7-chloro-1-[2(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro and 7-chloro-N-methyl-5-phenyl3H-1,4-benzodiazepin-2-amine 4-oxide (chlordiazepoxide) and a pharmaceutically acceptable salt of 7-chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide. Excerpt(s): The present invention is directed to pharmaceutical compositions, and primarily to topically applied ophthalmic compositions comprising as the active ingredient one or more gamma amino butyric acid agonist compounds. The pharmaceutical compositions are useful for reducing intraocular pressure in animals of the mammalian species. In another aspect, the present invention is directed to administering such formulations and compositions to animals of the mammalian species (including humans) for reducing intraocular pressure in the eye. Glaucoma is an optical neuropathy associated with elevated intraocular pressures which are too high for normal function of the eye, and results in irreversible loss of visual function. It is estimated in medical science that glaucoma afflicts approximately 2 per cent of the population over the age of forty years, and is therefore a serious health problem. Ocular hypertension, i.e. the condition of elevated intraocular pressure, which has not yet caused irreversible damage, is believed to represent the earliest phase of glaucoma. Many therapeutic agents have been devised and discovered in the prior art for the treatment or amelioration of glaucoma and of the condition of increased intraocular pressure which precedes glaucoma. Gamma amino butyric acid (H.sub.2 N(CH.sub.2).sub.3 COOH, GABA) is a natural metabolite, a break-down product of glutamine and a major inhibitory neurotransmitter. Its chemical structure can be described as an aliphatic carboxylic acid which carries an amino function on the terminal carbon of the aliphatic chain. Web site: http://www.delphion.com/details?pn=US06077839__
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Method for treating addiction to a drug of abuse employing an ACE inhibitor Inventor(s): Horovitz; Zola P. (Princeton, NJ), Sudilovsky; Abraham (Lawrenceville, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (Princeton, NJ) Patent Number: 5,093,129 Date filed: January 30, 1989 Abstract: A method is provided for treating addiction to a drug of abuse such as nicotine, cocaine or diazepam, by inhibiting appetitie or desire for such drug by administering an ACE inhibitor, such as captopril, fosinopril, zofenopril or SQ 29,852, alone or in combination with a calcium channel blocker such as diltiazem or nifedipine, over a prolonged period of treatment. Excerpt(s): The present invention relates to a method for treating addiction to a drug of abuse, such as nicotine, cocaine or diazepam, by administering an ACE inhibitor, such as captopril, SQ 29,852, zofenopril, fosinopril, enalapril or lisinopril, alone or in combination with a calcium channel blocker, such as diltiazem, nifedipine or verapamil. U.S. Pat. Nos. 4,046,889 and 4,105,776 to Ondetti et al discloses proline derivatives, including captopril, which are angiotensin converting enzyme (ACE) inhibitors useful for treating hypertension. U.S. Pat. No. 4,337,201 to Petrillo discloses phosphinylalkanoyl substituted prolines, including fosinopril, which are ACE inhibitors useful for treating hypertension. Web site: http://www.delphion.com/details?pn=US05093129__
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Method of thawing cryopreserved cells Inventor(s): Borland; Kermit M. (Shrewsbury, MA), Cain; Shawn P. (North Chelmsford, MA), Chandler; Barbara A. (Lexington, MA), Mullon; Claudy J-P. (Framingham, MA) Assignee(s): W.R. Grace & Co.-Conn. (Lexington, MA) Patent Number: 5,895,745 Date filed: September 25, 1996 Abstract: The invention features a method of processing cryopreserved cells by thawing and equilibrating the cells at warm temperatures (e.g., between 30.degree. C. and 43.degree. C). Either the cell suspension in the cryoprotective medium is thawed to a temperature between 35.degree. C. and 43.degree. C. or the cryoprotective medium is equilibrated with a culture medium at a temperature between 35.degree. C. and 43.degree. C., or both steps are carried out at the warm temperatures. By thawing and equilibrating the cryopreserved cells at warm temperatures, the viability, (especially after 3 hours of culture), and metabolic activity (i.e., diazepam metabolism) of the cells can be improved over traditional cold cell processing (i.e., at temperatures of between 2.degree. C. and 8.degree. C.). Excerpt(s): The invention relates to a method of processing cryopreserved cells. Cells can be preserved in a preservation medium (e.g., cryopreserved) so that they can be recovered alive for later use. For example, mammalian cells such as ova, spermatozoa, hepatocytes, and the like can be successfully cryopreserved. Cryopreservation techniques have been developed and improved over the last decade, however, the thawed cells are typically maintained at low temperatures (i.e., around 4.degree. C.) throughout processing until the cells are needed at full metabolic activity levels. Maintaining and manipulating thawed cells as cold cell suspensions allowed the cells to
Patents 113
be manipulated and transported to the site of action without risking loss of activity. The invention features a method of processing cryopreserved cells by thawing and equilibrating the cells at warm temperatures (e.g., between 30.degree. C. and 43.degree. C.). Most preferably, either the cell suspension in the cryoprotective medium is thawed to a temperature between 35.degree. C. and 43.degree. C. or the cryoprotective medium is equilibrated by adding a culture medium to dilute the cell suspension at a temperature between 35.degree. C. and 43.degree. C., or both steps are carried out at the warm temperatures. By thawing and equilibrating the cryopreserved cells at warm temperatures, the viability (especially after 3 hours of culture in an incubator), and metabolic activity (e.g., diazepam metabolism) of the cells can be improved over traditional cold cell processing (i.e., at temperatures of about 2.degree. C. to 8.degree. C.). Web site: http://www.delphion.com/details?pn=US05895745__ •
Nerve gas antidote Inventor(s): Bleyer; Holm (Trelleborger Weg 16, 0-200 Greifswald, DE), Sommer; Armin (Thomas-Mann-Strasse 8, 0-8122 Radebeul, DE) Assignee(s): none reported Patent Number: 5,298,504 Date filed: May 13, 1992 Abstract: A prophylactic pretreatment for nerve gas and pesticide poisons which can be administered orally and which comprises the following agents, in combination:a. Pyridostigmine (pyridostigmine bromide) or physostigmineb. Diazepam or clonazepamc. G 3063, Arpenal, Sycotrol (pipetabanate hydrochloride), caramiphen (caramiphene hydrochloride) or benactyzine (benactyzine hydrochloride).These agents may be administered in the form of a capsule which contains, for example, tablets, one a normal release dosage form and one or two in a slow release dosage form. Excerpt(s): The present invention relates to an oral prophylactic useful for minimizing injury from nerve gas poisons and related compounds such as organophosphorus pesticides. Nerve gas poisons are organic esters of substituted phosphoric acids. They inhibit cholinesterase enzymes and therefore are classified as anticholinesterase agents. Three active agents include Tabun (ethyl phosphorodimethylamidocyanidate-((CH.sub.3).sub.2 N)P(O)(CN)OC.sub.2 H.sub.5 --GA), Sarin (isopropyl methylphosphonofluoridate--CH.sub.3 P(O)(F)OCH(CH.sub.3).sub.2 --GB) and Soman (pinocolyl methylphosphonofluoridate--CH.sub.3 P(O)(F)OCH(CH.sub.3)C(CH.sub.3).sub.3 --GD). These compounds are highly volatile and easily disseminated in vapor form. They are readily absorbed through the lungs and eyes, and also the skin and intestinal tract without producing any irritation or other sensation. They are sufficiently potent that even brief exposure may be fatal. Depending on the concentration of the poison, death may occur in as little as one minute, or it may be delayed for 1-2 hours. Another category of such agents is the V agents, which are more potent, including VX. Web site: http://www.delphion.com/details?pn=US05298504__
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Pre-filled injection device comprising a barrel wherein a liquid diazepam formulation is accommodated Inventor(s): van den Heuvel; Johan G. (Amsterdam, NL) Assignee(s): Duphar International Research B.V. () Patent Number: 5,383,864 Date filed: December 14, 1992 Abstract: The invention relates to a pre-filled injection device, comprising (i) a barrel which is open at each end in which, before using the device, a liquid diazepam formulation is accommodated in a sealed manner and which comprises at least one rubber sealing member to seal the said formulation, and (ii) an injection needle or a needle connection at the front end of the barrel, said sealing member being manufactured at least substantially from bromobutyl rubber. Excerpt(s): The invention relates to a pre-filled injection device, comprising (i) a barrel which is open at each end and in which, before using the device, a liquid diazepam formulation is accommodated in a sealed manner and which comprises at least one rubber sealing member to seal the said formulation, and (ii) an injection needle or a needle connection means at the front end of the barrel. As is well-known, diazepam has good pharmacotherapeutic properties and is hence generally used as a sedative, as a hypnotic and as a muscle relaxant. Useful formulations for the parenteral administration of diazepam have meanwhile also become available. These liquid formulations comprise, in addition to diazepam and water, auxiliary substances in the form of organic solvents and/or formulation agents. As a result of this a solution or emulsion of diazepam which is suitable for parenteral administration can be obtained by a correct choice and dosing of the auxiliary substances. Such liquid diazepam formulations are often stored for considerable periods of time. As a result of this, suitable reservoirs are required in which the liquid can be accommodated in a sealed manner. Such reservoirs which usually are manufactured from glass or from a suitable synthetic material which is compatible with the diazepam formulation, are preferably sealingly closed by means of rubber sealing members. Web site: http://www.delphion.com/details?pn=US05383864__
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Process for preparing 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide and intermediates therefor Inventor(s): Barth; Wayne E. (East Lyme, CT), Nakanishi; Susumu (Niantic, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 3,998,883 Date filed: October 28, 1975 Abstract: A novel process is described for the preparation of 6-chloro-2-chloromethyl-4phenylquinazoline-3-oxide, a key intermediate in the synthesis of the known useful psychotherapeutic agents: chlorodiazepoxide and diazepam. This intermediate is prepared by the cyclization of 2-(1'-chloroimino-2'-chloromethyl)-5chlorobenzophenone, itself a new compound. This compound in turn is prepared by the chloroacetylation of 2-amino-5-chlorobenzophenone to 2-chloroacetamido-5chlorobenzophenone, another novel compound, and subsequent iminochloride formation.
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Excerpt(s): The 1,4-benzodiazepine 4-oxides: 7-chloro-2-methylamino-5-phenyl-3H-1,4benzodiazepine 4-oxide (chlorodiazepoxide) and 7-chloro-1,3-dihydro-1-methyl-5phenyl-2H-1,4-benzodiazepin-2-one (diazepam); have found wide clinical acceptance in the treatment of psychoneurotic states manifested by tension, anxiety, apprehension, fatigue, depression, agitation and acute alcohol withdrawal. The preparation of these compounds and intermediates therefor are described, for example, in U.S. Pat. Nos. 2,893,992; 3,311,612; 3,446,806; 3,340,253; 3,102,116; 3,109,843 and 3,136,815. This invention is concerned with a process for preparing 6-chloro-2-chloro-methyl-4phenylquinazoline, a key intermediate in the synthesis of the known useful psychotherapeutic agents: chlorodiazepoxide and diazepam. This intermediate is prepared by the cyclization of 2(1'-chloroimino-2'-chloromethyl)-5-chlorobenzophenone which in turn is prepared by the chloroacetylation of 2-amino-5-chlorobenzophenone to 2-chloroacetamido-5-chlorobenzophenone and subsequent iminochloride formation. A known process for the preparation of 7-chloro-2-methylamino-5-phenyl-3H-1,4benzodiazepine 4-oxide (chlorodiazepoxide) and 7-chloro-1,3-dihydro-1-methyl-5phenyl-2H-1,4-benzodiazepin-2-one (diazepam) involves the use of the important intermediate, 6-chloro-2-chloromethyl-4-phenylquinazoline-3-oxide. This compound, described in U.S. Pat. No. 2,893,992, is prepared by converting 2-amino-5chlorobenzophenone to the oxime (.alpha. and.beta.-oxime mixture) which is then treated with a mixture of hydrochloric and acetic acids to give the desired compound. This may be contacted with methylamine to yield chlorodiazepoxide or in a series of steps to give diazepam. Web site: http://www.delphion.com/details?pn=US03998883__ •
Radioreceptor assay for benzodiazepines in plasma and other biological specimens Inventor(s): Paul; Steven M. (Silver Spring, MD), Skolnick; Phil (Bethesda, MD) Assignee(s): United States of America (Washington, DC) Patent Number: 4,239,744 Date filed: October 10, 1978 Abstract: A rapid and sensitive radioreceptor assay for measuring benzodiazepines in plasma and other biological specimens is described. This method is based on the competition between [.sup.3 H] diazepam or tritiated flunitrazepam and pharmacologically active benzodiazepines present in plasma, for binding sites on rat brain synaptosomal membranes. No interference is obtained with drug-free plasma or plasma samples containing high concentrations of other commonly used drugs. High correlations (r=0.98; p<0.001) were obtained between the "diazepam equivalents" measured in plasma using the radioreceptor assay and the levels of diazepam and Ndemethyl diazepam obtained by gas-liquid chromatography. The radioreceptor assay is rapid, sensitive, specific, and requires no sophisticated equipment or methodology. It should therefore prove useful in monitoring blood benzodiazepine levels for both therapeutic and toxicologic purposes. Excerpt(s): This invention relates to radioreceptor assays of drugs and, in particular, to a rapid and sensitive radioreceptor assay for benzodiazepines in blood plasma and other biological specimens. The benzodiazepines, which include diazepam, flurazepam, and chloridiazepoxide, comprise the most widely prescribed class of compounds in current therapeutic use (D. J. Greenblatt and R. I. Shader: Benzodiazepines in Clinical Practice 1974). Like many other drugs, the benzodiazepines show a wide range of blood levels among different individuals on a standard dose (ibid, Greenblatt et al). Further, there is
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some evidence indicating a relationship between the therapeutic and/or side effects of these drugs and their blood level (ibid, Greenblatt et al). These observations suggest that the clinical utility of these agents may be enhanced by blood level monitoring. Such monitoring is currently performed by gas-liquid chromatography, often coupled with electroncapture detection (GLC/EC) [J. A. Zingales: Diazepam metabolism during chronic medication, unbound fraction in plasma, erythrocytes and urine. J. Chromatogr. 75:55-78 (1975); D. M. Hailey: Chromatography of the 1,4-benzodiazepines. J. Chromatogr. 98: 527-568,1974; and M. Linnoila and F. Dorrity: Rapid gas chromatographic assay of serum diazepam, N-desmethyldiazepam, and Ndesalkylfurazepam. Acta pharmacol. et. toxicol. 41: 458-464, 1977]. These methods, while sufficiently sensitive, have not achieved routine clinical use because of the sophisticated equipment required and the need for sample extraction prior to analysis. In addition, the extensive metabolism of benzodiazepines to a number of pharmacologically active metabolites has made monitoring of the parent drug alone or any one active metabolite of questionable significance, while measuring all metabolites is often too impractical for routine clinical use. The recent identification of high affinity, stereospecific, binding sites for [.sup.3 H] diazepam in the mammalian central nervous system [C. Braestrup, A. Albrechtsen and R. F. Squires: High densities of benzodiazepine receptors in human cortical areas: Nature 269: 702-704, (1977), and H. Mohler and T. Okada: Benzodiazepine receptor: demonstration in the central nervous system. Science 198: 849-851, (1977)], affords an alternative method for measuring plasma benzodiazepines which is simple, rapid, and requires little equipment beyond that which is already available in most clinical laboratories. These binding sites are specific for benzodiazepines (ibid, Braestrup et al and Mohler et al), and the inhibition of binding by other benzodiazepines is highly correlated with clinical potency (ibid, Braestrup et al and Mohler et al). Thus, the radioreceptor technique permits the simultaneous measurement of all of the benzodiazepine compounds which bind the receptor, and thus, provides a total estimate of all pharmacologically active forms of the drug--a distinct advantage over existing chromatographic techniques. Web site: http://www.delphion.com/details?pn=US04239744__ •
Radioreceptor assay for benzodiazepines in saliva Inventor(s): Rosenblatt; Jack E. (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 4,431,742 Date filed: March 30, 1981 Abstract: A radioreceptor assay for benzodiazepines in saliva which comprises measuring the diminution of attachment of a known quantity of radio labeled benzodiazepine to a receptor carrier in the presence of an unknown quantity of unlabeled benzodiazepine in a known amount of human saliva. Benzodiazepines are selected from the following oft-utilized drugs which are also representative types of benzodiazepine; namely, diazepam (Valium), chlordiazepoxide (Librium), nitrazepam (Benzalin), oxazepam (Serax), flurazepam (Dalmane), and clorazepate.Competitive receptors suitable for the present benzodiazepine radioreceptor assay are from fresh rat frontal cortex. Utilizable receptors are whole brain cortex, human cortex, and striatum. Excerpt(s): The benzodiazepines are the most commonly used prescription drugs in this country. They are commonly used to treat anxiety and insomnia and are increasingly
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being used to treat alcohol withdrawal symptoms and epileptic seizures. Routine monitoring of benzodiazepine concentrations would be desirable for many reasons. Patient dose requirements vary widely due to the wide range of blood levels reported following the same dose. Because benzodiazepine side effects, such as lethality when mixed with alcohol, and the risk of physiological and psychological dependence are apparently does related, patients should be maintained on the lowest effective therapeutic dose. Although threshold levels must be attained for therapeutic efficacy, excessive levels may cause clinical worsening. U.S. Pat. No. 4,083,948 Davis et al. (Hoffmann-LaRoche) is a radioimmunoassay for benzodiazepines using preferably.sup.125 I-labeled 4'-hydroxy derivatives of these compounds as tracers. U.S. Pat. No. 4,119,709 Holub is a diagnostic test based on competitive binding where there is a difference for the radioactive labeled form of the substance between liquid and solid phases. Web site: http://www.delphion.com/details?pn=US04431742__ •
Sustained release pharmaceutical capsules Inventor(s): Sheth; Prabhakar R. (Pearl River, NY), Tossounian; Jacques L. (Pine Brook, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,126,672 Date filed: September 19, 1977 Abstract: Sustained release pharmaceutical capsules suitable for oral administration and particularly suitable for sustained release therapy with certain benzodiazepines, e.g. chlordiazepoxide and diazepam, are disclosed. The formulation contained in the disclosed capsules is hydrodynamically balanced to be buoyant in gastric fluid thereby remaining buoyant in the gastric fluid until substantially all of the medicament therein has been released. Excerpt(s): The convenience of administering a single dose of medication which releases active ingredient over an extended period of time as opposed to the administration of a number of single doses at regular intervals has long been recognized in the pharmaceutical art. The advantage to the patient and clinician in having consistent and uniform blood levels of medication over an extended period of time are likewise recognized. In most sustained release preparations known to the pharmaceutical art, medicinal agents are either coated with varying thicknesses of some type of relatively insoluble material or are imbedded into a rigid lattice of resinous material. In such preparations, the object is to continuously provide drug for absorption into the blood stream to replace the amount eliminated while the dosage form is passing through the gastrointestinal tract of the patient. The conventional approaches to sustained release formulation briefly outlined above can be disadvantageous in that certain classes of active ingredients are not suited to absorption during passage through the gastrointestinal tract due to their physiochemical properties and/or favorable sites of absorption. For example, most acidic medicaments are principally absorbed from the stomach whereas most basic medicaments are absorbed primarily from the intestines. Most medicaments will undergo varying degrees of change in solubility by passage from the acutely acidic conditions of the stomach to the neutral to alkaline conditions of the intestines. For example, ferrous salts are more soluble in the stomach than in the intestines. Finally, there are medicaments, e.g. antacids, which are intended to act in the stomach and therefore lose most beneficial properties when they pass into the intestines.
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It is readily apparent in view of the above considerations that a large number of medicaments are not amenable to conventional sustained release formulations which are not retained in the stomach and which release medicament in the intestines. It is equally apparent that a sustained release formulation which is retained in the stomach and which slowly releases medicament over an extended period of time would be eminently suited to such medicaments. Such a sustained release formulation is provided by the present invention. Web site: http://www.delphion.com/details?pn=US04126672__ •
Treatment of colic and teething Inventor(s): Thornfeldt; Carl R. (1054 NW. 2nd Ave., Ontario, OR 97914), Thornfeldt; Robert E. (1021 SW. 5th Ave., Ontario, OR 97914) Assignee(s): none reported Patent Number: 4,889,850 Date filed: December 28, 1988 Abstract: Teething and colic are alleviated in infants and toddlers by the administration of a combination of an antihistamine and a benzodiazepine having sedative hypnotic activity. An exemplary antihistamine is hydroxyzine pamoate, and an exemplary benzodiazepine is diazepam. Excerpt(s): This invention relates to the treatment of colic and teething, two conditions that afflict a significant portion of babies and young children. Colic is a symptom complex characterized by paroxysms of presumably severe abdominal pain and crying with irritability and fussing in an otherwise healthy infant. These episodes usually occur during the first one and one-half to nine months of life and afflict up to 40% of infants. There are a number of known and presumed causes of this condition including milk allergy, under feeding, over feeding, high carbohydrate diet, ineffective burping, excessively large holes in the nipple, excess air sucked in, changes in handling, feeding, and sleeping routines, stimulus overload, anxious parents, and gastrointestinal smooth muscle cramping. To be effective, therapeutic drugs must do more than merely relieve pain, since pain plays a minor role if any in colic. Teething is another symptom complex occurring in nearly all infants and toddlers to some degree at three to eighteen months of age. Teething is characterized by pain, tenderness, edema, excess salivation, irritability and insomnia. These symptoms result from migration and eventual eruption of deciduous teeth through the oral mucosa. Web site: http://www.delphion.com/details?pn=US04889850__
Patent Applications on Diazepam 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 diazepam:
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This has been a common practice outside the United States prior to December 2000.
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Delivery of diazepam through an inhalation route Inventor(s): Rabinowitz, Joshua D.; (Mountain View, CA), Zaffaroni, Alejandro C.; (Atherton, CA) Correspondence: Richard R. Eckman; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030091511 Date filed: May 15, 2002 Abstract: The present invention relates to the delivery of diazepam through an inhalation route. Specifically, it relates to aerosols containing diazepam that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of diazepam. In a method aspect of the present invention, diazepam is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of diazepam, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering diazepam through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of diazepam; and, b) a device that forms a diazepam containing aerosol from the composition, for inhalation by the mammal. Excerpt(s): This application claims priority to U.S. provisional application Ser. No. 60/345,882 entitled "Delivery of Diazepam Through an Inhalation Route," filed Nov. 9, 2001, Rabinowitz, the entire disclosure of which is hereby incorporated by reference. The present invention relates to the delivery of diazepam through an inhalation route. Specifically, it relates to aerosols containing diazepam that are used in inhalation therapy. VALIUM.RTM. is a composition currently marketed for the management of anxiety disorders and the relief of anxiety symptoms. It is administered both orally and by injection. The active ingredient in VALIUM.RTM. is diazepam, which is typically provided in doses of 2 mg to 20 mg. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel human DBI/ACBP-like protein Inventor(s): Au-Young, Janice; (Berkeley, CA), Goli, Surya K.; (Sunnyvale, CA), Hillman, Jennifer L.; (San Jose, CA) Correspondence: Incyte Genomics, INC.; Patent Department; 3160 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20020068825 Date filed: May 14, 2001 Abstract: The present invention provides polynucleotides which identify and encode a novel human Diazepam binding inhibitor/acyl-CoA binding protein (DBI/ACBP)-like protein (DBIH). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding DBIH. The invention also provides for the use of substantially purified DBIH for drug delivery as well as for the production of recombinant proteins for the treatment of diseases associated with the expression of DBIH. Additionally, the invention provides for the use of antisense
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molecules to DBIH in the treatment of diseases associated with the expression of DBIH. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotides which hybridize with naturally occurring sequences encoding DBIH and antibodies which specifically bind to the protein. Excerpt(s): This application is a continuation application of U.S. application Ser. No. 08/937,823 filed Sep. 25, 1997, which is a divisional of U.S. application Ser. No. 08/700,626, filed Aug. 16, 1996, now U.S. Pat. No. 5,734,038, issued Mar. 31, 1998, entitled NOVEL HUMAN DBI/ACBP-LIKE PROTEIN, all of which applications and patents are hereby incorporated herein by reference. The present invention relates to nucleic acid and amino acid sequences of a novel human DBI/ACBP-like protein and to the use of these sequences in the diagnosis, study, prevention and treatment of disease. Diazepam binding inhibitor/acyl-CoA binding protein (DBI/ACBP)-like protein is a 10 kdal protein found in species ranging from yeast to mammals. It is expressed in a variety of organs and tissues. Originally, DBI was purified from rat brain based on its ability to displace diazepam from type A gamma-aminobutyrate (GAB.sub.A) receptors (Guidotti et al. (1983) Proc. Natl. Acad. Sci. USA 80:3531-3535). An acyl-Coenzyme A (acyl-CoA) binding protein (ACBP) subsequently purified from liver was found to be identical to DBI (Mikkelsen, J. et al. (1987) Biochem. J. 245:857-861). The protein was known as endozepine, DBI, or ACBP, but it is now generally referred to as DBI/ACBP. DBI/ACBP, and polypeptides derived from it, have been implicated in multiple biological processes, such as 1) GABA.sub.A/benzodiazepam receptor modulation, 2) acyl-CoA metabolism, 3) steroidogenesis, and 4) insulin secretion (reviewed in Knudsen J et al (1993) Mol Cell Biochem 123:129-138). 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 diazepam, 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 “diazepam” (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 diazepam. You can also use this procedure to view pending patent applications concerning diazepam. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON DIAZEPAM Overview This chapter provides bibliographic book references relating to diazepam. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on diazepam include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “diazepam” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “diazepam” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “diazepam” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Beyond Valium: The Brave New World of Psycochemistry by Seymour Rosenblatt; ISBN: 0399125779; http://www.amazon.com/exec/obidos/ASIN/0399125779/icongroupinterna
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Chlordiazepoxide and diazepam: a report on the supply of chlordiazepoxide and diazepam; ISBN: 0102197733; http://www.amazon.com/exec/obidos/ASIN/0102197733/icongroupinterna
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Good Chemistry: The Life and Legacy of Valium Inventor Leo Sternbach by Alex Baenninger, Alex Baenninger; ISBN: 0071426175; http://www.amazon.com/exec/obidos/ASIN/0071426175/icongroupinterna
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Stopping Valium and Ativan, Centrax, Dalmane, Librium, Paxipam, Restoril, Serax, Tranxene, Xanax by Eve Bargman; ISBN: 0937188123; http://www.amazon.com/exec/obidos/ASIN/0937188123/icongroupinterna
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Stopping Valium: And Ativan, Centrax, Dalmane, Librium, Paxipam, Restoril, Serax, Tranxene, Xanax by Eve and Bargmann, et al; ISBN: 0446375829; http://www.amazon.com/exec/obidos/ASIN/0446375829/icongroupinterna
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Valium & Other Downers (Junior Drug Awareness) by Cindy Dyson, et al (2000); ISBN: 0791052060; http://www.amazon.com/exec/obidos/ASIN/0791052060/icongroupinterna
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Valium and Other Tranquilizers (Encyclopedia of Psychoactive Drugs. Series 1) by Solomon H. Snyder (Editor), Gail Winger; ISBN: 0877547599; http://www.amazon.com/exec/obidos/ASIN/0877547599/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “diazepam” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
1st International Symposium on "Rectal Diazepam for Acute Therapy": June 4th, 1982, Frankfurt Author: Breimer, Douwe D.,; Year: 1989; München: Zuckschwerdt, c1983; ISBN: 3886030520
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Developmental immunotoxicity of diazepam in prenatally treated weanling Wistar rats Author: Loveren, Hendrik van,; Year: 1964; Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu, [1999]
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Diazepam attenuates long-term behavioral incapacitation in Rhesus monkeys exposed to nerve agents Author: Larsen, Thomas.; Year: 1995; Aberdeen Proving Ground, MD (21010-5425): U.S. Army Medical Research, Institute of Chemical Defense, [1995]
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Diazepam in anaesthesia; report of the proceedings of a symposium held at the Royal Society of Medicine, London, on 30 June, 1967, sponsored by Roche Products Limited. Edited by Peter F. Knight and C. G. Burgess. Author: Burgess, C. G.; Year: 1973; Bristol, Wright, 1968
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Estimate of the lowest dose of diazepam required to treat soman-induced convulsions in rhesus monkeys pretreated with pyridostigmine and treated with atropine, pralidoxime chloride and diazepam Author: Von Bredow, Jurgen D.; Year: 1990; Aberdeen Proving Ground, MD: U.S. Army Medical Research Institute of Chemical Defense, [1992]
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Extension of the OECD 414 rat teratogenicity protocol by increasing the duration of treatment and introduction of parameters of immunotoxicity: an exploratory study
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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using diazepam as a model compound Author: Waal, E. J. de.; Year: 1998; Bilthoven: National Institute of Public Health and the Environment, [1998] •
Optimal blood sampling times for diazepam pharmacokinetics in rhesus monkeys Author: Corcoran, Kevin D.; Year: 1992; Fort Detrick, Md.: US Army Medical Research and Development Command, [1989]
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Stopping Valium and Ativan, Centrax, Dalmane, Librium, Paxipam, Restoril, Serax, Tranxene, Xanax Author: Bargmann, Eve.; Year: 1983; Washington, D.C.: The Group, c1982; ISBN: 093788123
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Symposium on Diazepam ("Valium") held at Cambridge, June 1964. Edited by P. Hume Kendall. Author: Kendall, P. Hume (Patrick Hume); Year: 1981; London, Baillière, Tindall and Cassell [1964]
Chapters on Diazepam In order to find chapters that specifically relate to diazepam, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and diazepam 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 “diazepam” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on diazepam: •
Oral Medications Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 81-112. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail:
[email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on oral medications used to treat IC is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. Oral medications, used alone or in combination with other medications, will improve symptoms in most patients with IC. Patients may still have some symptoms while on oral medications, but they may be improved to the point where they wish to wait before undergoing more invasive therapy. Most of the medications used cause few significant side effects. The author notes that most of the medications discussed in this chapter have been used for many years but for other purposes. Medications and dosages may need to be changed due to side effects or poor responses. The author first discusses medications thought to coat the bladder's surface, including pentosan polysulfate sodium (Elmiron), chondroitin sulfate, and glucosamine. The author then discusses the use of antidepressants (primarily to reduce pain), including amitriptyline (Elavil); selective serotonin reuptake inhibitors (SSRIs); antihistamines, including hydroxyzine (Atarax, Vistaril); cromolyn sodium (Gastrocrom); cimetidine (Tagamet); antiseizure
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medications, including gabapentin (Neurontin), and carbamazepine (Tegretol); nonsteroidal antiinflammatory drugs (NSAIDs); immunosuppressants, including steroids; muscle relaxants, notably diazepam (Valium); narcotic therapy; urinary anesthetics, including phenazopyridine hydrochloride (Pyridium), atropine sulfate, benzoic acid, hyoscyamine, methenamine, methylene blue, and phenyl salicylate (Urised); anticholinergic therapy; L arginine; calcium channel blockers, including nifedipine (Procardia); and alpha blockers. The author reviews the use of each of these drugs, along with the hypothesis about why they may be of use in IC. •
Drugs Used for Vertigo and Vomiting Source: in Bennett, D.R., ed. Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, Division of Toxicology. 1994. p. 439-464. Contact: Available from American Medical Association. Division of Drugs and Toxicology, 515 North State Street, Chicago, IL 64610. (312) 464-500. ISBN: 0899706029. PRICE: $78.00 for AMA members, $98.00 for nonmembers. Summary: This chapter discusses drugs that are effective in combating vertigo or nausea and vomiting. The vertigo section includes a description of vertigo; its causes; subjective vertigo; drug-induced vertigo; and Meniere's disease. The section also includes a discussion of drug selection for antivertigo drugs. Drugs discussed include scopolamine; antihistaminic drugs; antianxiety agents and antidepressants; diazepam (Valium); droperidol (Innovar); and fentanyl citrate (Sublimaze). The chapter concludes with the chemical formation, and a discussion of uses, adverse reactions and precautions, and dosage and preparations for each of the pharmaceuticals discussed. 1 table. 101 references.
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Drugs Meant to Block Symptoms Temporarily Source: in Haybach, P.J. Meniere's Disease: What You Need to Know. Portland, OR: Vestibular Disorders Association. 1998. p. 163-170. Contact: Available from Vestibular Disorders Association. P.O. Box 4467, Portland, OR 97208-4467. (800) 837-8428. E-mail:
[email protected]. Website: www.vestibular.org. PRICE: $24.95 plus shipping and handling. ISBN: 0963261118. Summary: This chapter is from a book that provides information for people who have or suspect they have Meniere's disease and want to know more about its diagnosis and treatment, as well as strategies for coping with its effects. Written in nontechnical language, the chapter discusses the use of drugs meant to block symptoms temporarily. The author groups these drugs into three categories: motion sickness drugs, drugs used for nausea and vomiting, and anti-anxiety anti-vertigo drugs. For each category, the author briefly reviews the drugs included, limitations as to who can use the drugs, possible side effects, and strategies for safe and effective drug use. Drugs covered include meclizine (Antivert), dimenhydrinate (Dramamine), diphenhydramine (Benadryl), scopolamine, promethazine (Phenergan), prochlorperazine (Compazine), trimethobenzamide (Tigan), diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin). 10 references.
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Dental Phobias Source: in Enoch, D.; Jagger, R. Psychiatric Disorders in Dental Practice. Newton, MA: Butterworth-Heinemann. 1994. p. 73-76.
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Contact: Available from Butterworth-Heinemann. 313 Washington Street, Newton, MA 02158-1626. (800) 366-2665 or (617) 928-2500; Fax (617) 933-6333. PRICE: $35.00 plus shipping and handling. ISBN: 0723610061. Summary: This chapter on dental phobias is from a book on the psychiatric disorders most commonly encountered by the dentist. Topics covered include a classification system for dental fears, and the treatment of phobias and people with dental phobias. The authors stress that the majority of patients with dental phobias can be dealt with by the general practitioner using a sympathetic approach that may be equated with supportive psychotherapy. The practitioner may supplement this with short-term preoperative anxiolytics such as diazepam. The authors briefly consider the impact of patients with phobia on the dental practice. 1 table. 7 references.
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CHAPTER 7. MULTIMEDIA ON DIAZEPAM Overview In this chapter, we show you how to keep current on multimedia sources of information on diazepam. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Bibliography: Multimedia on Diazepam The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in diazepam (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on diazepam: •
A Technique of intravenous dissociation for office surgery using valium and ketamine [videorecording]: breast augmentation and abdominoplasty: tranquility in the office operating room Source: Educational Foundation, American Society of Plastic and Reconstructiv; Year: 1980; Format: Videorecording; [Chicago]: The Foundation, 1980
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CHAPTER 8. PERIODICALS AND NEWS ON DIAZEPAM Overview In this chapter, we suggest a number of news sources and present various periodicals that cover diazepam.
News Services and Press Releases One of the simplest ways of tracking press releases on diazepam 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 “diazepam” (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 diazepam. 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 “diazepam” (or synonyms). The following was recently listed in this archive for diazepam: •
FDA says diazepam auto-injector ANDAs can be approved Source: Reuters Industry Breifing Date: December 27, 2002
•
Rectal diazepam gel safely aborts acute repetitive seizures Source: Reuters Industry Breifing Date: December 24, 2002
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•
Roche stops selling Valium in UK Source: Reuters Industry Breifing Date: January 30, 2002
•
Company stops selling Valium in UK Source: Reuters Health eLine Date: January 30, 2002
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Rectal diazepam decreases emergency treatment of children with seizures Source: Reuters Industry Breifing Date: December 18, 2000
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Rectal diazepam gel safe and effective for treatment of acute repetitive seizures in children Source: Reuters Medical News Date: May 20, 1999
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At-home administration of rectal diazepam gel effective for acute repetitive seizures Source: Reuters Medical News Date: June 25, 1998
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Diazepam gel treats seizures at home Source: Reuters Health eLine Date: June 24, 1998
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Diazepam Inhibits HIV-1 Expression In Human Brain Cells Source: Reuters Medical News Date: November 10, 1997
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Elan Diazepam Rectal Gel For Epilepsy Gets FDA Approval Source: Reuters Medical News Date: August 01, 1997
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Diazepam May Increase Risk Of Falling In The Elderly Source: Reuters Medical News Date: April 17, 1997
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FDA Advisory Committee Recommends New Formulation Of Diazepam For Home Use Source: Reuters Medical News Date: November 18, 1996 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.
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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 “diazepam” (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 “diazepam” (or synonyms). If you know the name of a company that is relevant to diazepam, 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 “diazepam” (or synonyms).
Academic Periodicals covering Diazepam Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to diazepam. In addition to these sources, you can search for articles covering diazepam 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
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periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for diazepam. 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 diazepam. 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 diazepam: Benzodiazepines •
Systemic - U.S. Brands: Alprazolam Intensol; Ativan; Dalmane; Diastat; Diazepam Intensol; Dizac; Doral; Halcion; Klonopin; Librium; Lorazepam Intensol; Paxipam; ProSom; Restoril; Serax; Tranxene T-Tab; Tranxene-SD; Tranxene-SD Half Strength; Valium; Xanax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202084.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to diazepam by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “diazepam” (or synonyms) into the search box, and click “Submit Query.” When you receive your results,
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note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for diazepam: •
Diazepam viscous solution for rectal administration http://www.rarediseases.org/nord/search/nodd_full?code=489
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “diazepam” (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 19283 83 677 14 0 20057
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “diazepam” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Diazepam In the following section, we will discuss databases and references which relate to the Genome Project and diazepam. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “diazepam” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for diazepam: •
Diazepam Binding Inhibitor Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?125950 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “diazepam” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “diazepam” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on diazepam 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 diazepam. 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 diazepam. 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 “diazepam”:
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•
Other guides Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html Panic Disorder http://www.nlm.nih.gov/medlineplus/panicdisorder.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.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 diazepam. 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: •
Interaction of Prescription Drugs With Commonly-Abused Drugs Among Dialysis Patients Source: American Kidney Fund Newsletter for Health Professionals. 7(1): [p. 9-14]. 1990. Summary: This article consists of a comprehensive chart detailing the effects of commonly abused drugs on dialysis patients. This chart is intended as a reference guide, and pulls together information heretofore unavailable in a single place. For each of fifteen drugs, the common name, generic name, class of drug, actions, indictions, methods of abuse, side effects, signs and symptoms of overdose, interactions, capability of dialyzing (if known), addictive potential, and signs and symptoms of withdrawal are provided. The fifteen drugs covered are: heroin; morphine; Demerol; codeine; Talwin; Quaalude; Nembutal; Seconal; phenobarbital; Restoril (temaepam); alium (diazepam); Dalmane (flurazepam); crank and ice (amphetamine, methamphetamine); cocaine; and crack (cocaine).
•
Drugs and Tinnitus Source: London, England: Royal National Institute for Deaf People. 1998. 6 p. Contact: Available from RNID Helpline. P.O. Box 16464, London EC1Y 8TT, United Kingdom. 0870 60 50 123. Fax 0171-296 8199. E-mail:
[email protected]. Website: www.rnid.org.uk. Also available from RNID Tinnitus Helpline. Castle Cavendish
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Works, Norton Street, Radford, Nottingham NG7 5PN, United Kingdom. 0345 090210. Fax 0115-978 5012. E-mail:
[email protected]. PRICE: Single copy free. Summary: This fact sheet from the Royal National Institute for Deaf People (RNID) discusses the relationship between drugs and tinnitus (ringing or noises in the ears). The fact sheet reports on a brief survey of four categories of drugs for tinnitus, drugs for the effects of tinnitus, drugs to relieve other conditions that may be causing the tinnitus, and drugs that might cause or aggravate tinnitus. These include lignocaine, carbamazepine, clonazepam, tocainide, flecainide, mexiletine, frusemide, phenytoin sodium, vigabatrin, nimodipine, alprazolam, betahistine, tranquilizers, diazepam, antidepressants, diuretics, antihypertensives, decongestants and antihistamines, zinc sulfate, sodium fluoride, aspirin, quinine, loop diuretics, aminoglycoside antibiotics, and neomycin. The fact sheet emphasizes the importance of working closely with health care providers before changing any medications. The fact sheet concludes with information on the RNID Tinnitus Helpline (in Nottingham, UK), which is also accessible online at
[email protected]. The RNID website is at www.rnid.org.uk. •
Motor Neuron Disease Source: New Fairfield, CT: National Organization for Rare Disorders. 1994. [4 p.]. Contact: National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518; TDD (203) 746-6927; (800) 999-NORD. PRICE: Free for 1st request, $4.00 per copy thereafter. Summary: This fact sheet summarizes information on motor neuron diseases (MND's), including a brief definition and synonyms for the disease, symptom progression, possible causes, the population affected, standard and investigational therapies, and related disorders. MND is a group of serious disorders characterized by progressive degeneration of motor neurons (neurons combined to form nerves that control the behavior of muscles). Symptoms are characterized by muscle weakness, atrophy, and normal intellectual functioning. There are several forms of MND, including amyotrophic lateral sclerosis (Lou Gehrig's disease), primary lateral sclerosis, WerdnigHoffmann disease, and Kugelberg-Welander syndrome. The exact etiology of MND is unknown. In general, all forms of the disease are rare, affecting different populations. Standard therapies include the use of drugs symptoms such as baclofen, quinine, and diazepam to control muscle; various respiratory aids; devices to help the patient continue daily living activities; and genetic counseling for patients and families with a hereditary form of MND. This fact sheet includes a list of resources on MND. The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to diazepam. 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.
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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
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 diazepam. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with diazepam. 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 diazepam. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “diazepam” (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
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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 “diazepam”. 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 “diazepam” (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 “diazepam” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.25
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
25
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
•
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/
•
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/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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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
•
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/
•
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/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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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
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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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
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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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/
•
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
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
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
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
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/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on diazepam: •
Basic Guidelines for Diazepam Diazepam overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002629.htm
•
Signs & Symptoms for Diazepam Bluish colored lips and fingernails Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Blurred vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm
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Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Double vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Incoordination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Ringing in the ears Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003043.htm Stomach upset Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Stupor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Weariness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm •
Diagnostics and Tests for Diazepam Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm
Online Glossaries 161
•
Background Topics for Diazepam Labored breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Unconscious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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DIAZEPAM DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acepromazine: A phenothiazine that is used in the treatment of psychoses. [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] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [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] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acyl: Chemical signal used by bacteria to communicate. [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
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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] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] 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] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH]
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Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] Alcohol Drinking: Behaviors associated with the ingesting of alcoholic beverages, including social drinking. [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] Alfentanil: A short-acting opioid anesthetic and analgesic derivative of fentanyl. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] 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,
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magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [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 Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
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] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [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] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [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] Ampulla: A sac-like enlargement of a canal or duct. [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]
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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] 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] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [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-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
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Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign 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] Antidiuretic: Suppressing the rate of urine formation. [EU] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antihypertensive: An agent that reduces high blood pressure. [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] Antimycotic: Suppressing the growth of fungi. [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,
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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] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [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] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH]
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Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [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] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiometry: The testing of the acuity of the sense of hearing to determine the thresholds of the lowest intensity levels at which an individual can hear a set of tones. The frequencies between 125 and 8000 Hz are used to test air conduction thresholds, and the frequencies between 250 and 4000 Hz are used to test bone conduction thresholds. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autogenic: A type of succession when the developing vegetation itself is the cause for the succession. [NIH] Autonomic: Self-controlling; functionally independent. [EU]
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Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Barbital: A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benactyzine: A centrally acting muscarinic antagonist. Benactyzine has been used in the treatment of depression and is used in research to investigate the role of cholinergic systems on behavior. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH]
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Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Betahistine: N-Methyl-2-pyridineethanamine. A physiological histamine analog vasodilator agent that also acts as a histamine H1 receptor agonist. It is used in Meniere's disease and in vascular headaches but may exacerbate bronchial asthma and peptic ulcers. [NIH] Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [NIH] Bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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]
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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] Body Regions: Anatomical areas of the body. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Conduction: Sound transmission through the bones of the skull to the inner ear. [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] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [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]
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Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell
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membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] 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] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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 Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH]
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Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] 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 hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawl. [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] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH]
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Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]
Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other
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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] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [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] Clopenthixol: A thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the
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action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [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]
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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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] 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] Conscious Sedation: An alternative to general anesthesia in patients for whom general anesthesia is refused or considered inadvisable. It involves the administering of an antianxiety drug (minor tranquilizer) and an analgesic or local anesthetic. This renders the patient free of anxiety and pain while allowing the patient to remain in verbal contact with the physician or dentist. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]
Continence: The ability to hold in a bowel movement or urine. [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]
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Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
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] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as
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antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack. [NIH] Cryoprotective: Any substance added to a living tissue for improving its survival during frozen preservation. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] 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]
Cystitis: Inflammation of the urinary bladder. [EU] 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] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in
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that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] 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] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
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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. 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] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] 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] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] 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 Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of
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the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimenhydrinate: A drug combination that contains diphenhydramine and theophylline. It is used for treating vertigo, motion sickness, and nausea associated with pregnancy. It is not effective in the treatment of nausea associated with cancer chemotherapy. [NIH] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] 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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the
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back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] 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] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH]
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Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] 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] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU]
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Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may
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result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagogastroduodenoscopy: Exam of the upper digestive tract using an endoscope. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical 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] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etomidate: Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic. [NIH]
Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH]
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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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Nerve Diseases: Diseases of the facial nerve or nuclei. Pontine disorders may affect the facial nuclei or nerve fascicle. The nerve may be involved intracranially, along its course through the petrous portion of the temporal bone, or along its extracranial course. Clinical manifestations include facial muscle weakness, loss of taste from the anterior tongue, hyperacusis, and decreased lacrimation. [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH]
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Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Ferrets: Semidomesticated variety of European polecat much used for hunting rodents and/or rabbits and as a laboratory animal. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] 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 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] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH] Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. [NIH] Flunitrazepam: Benzodiazepine with pharmacologic actions similar to those of diazepam. The United States Government has banned the importation of this drug. Steps are being taken to reclassify this substance as a Schedule 1 drug with no accepted medical use. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH]
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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] Flurazepam: A benzodiazepine derivative used mainly as a hypnotic. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-hydroxybutyrate: Anxiolytic. [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] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [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]
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Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Dosage: The number of copies of a given gene present in a cell or nucleus. An increase in gene dosage can result in the formation of higher levels of gene product, provided that the gene is not subject to autogenous regulation. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Glafenine: An anthranilic acid derivative with analgesic properties used for the relief of all types of pain. [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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
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Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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] Glycopyrrolate: A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth
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of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [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] 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] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Head Movements: Voluntary or involuntary motion of head that may be relative to or independent of body; includes animals and humans. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH]
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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] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Heterotropic: Of organisms that cannot live without an external source of organic food. [NIH] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH]
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Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [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] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hyperacusis: An abnormally disproportionate increase in the sensation of loudness in response to auditory stimuli of normal volume. Cochlear diseases; vestibulocochlear nerve diseases; facial nerve diseases; stapes surgery; and other disorders may be associated with this condition. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperemesis: Excessive vomiting. [EU] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU]
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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] 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] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune function: Production and action of cells that fight disease or infection. [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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience
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with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubator: Consists of a transparent plastic cubicle, electrical heating equipment, safety and warning devices, and oxygen and air filtering and regulating apparatus; an enclosed transparent boxlike apparatus for housing prematurely born babies under optimum conditions. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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]
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Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] 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] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] 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] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intravenous Anesthetics: The systemic administration of an anesthetic drug via an injection into the vein. [NIH]
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Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isopropyl: A gene mutation inducer. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [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] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU]
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Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] 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] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [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]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number
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3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] 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] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU]
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Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Meclizine: A histamine H1 antagonist used in the treatment of motion sickness, vertigo, and nausea during pregnancy and radiation sickness. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Mefenamic Acid: A non-steroidal anti-inflammatory agent with analgesic, antiinflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase. [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] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH]
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Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] 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 Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methohexital: An intravenous anesthetic with a short duration of action that may be used for induction of anesthesia. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [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] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH]
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Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] 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] Mitotic: Cell resulting from mitosis. [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]
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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] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [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 Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Neurons: Neurons which activate muscle cells. [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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU]
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Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutism: Inability or refusal to speak. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH]
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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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [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] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular 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] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH]
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Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrophil: A type of white blood cell. [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] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic 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] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic. [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] 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] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [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] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a
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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] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [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] Orofacial: Of or relating to the mouth and face. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU]
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Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] 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] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. [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]
Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancuronium: A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than curare but has less effect on the circulatory system and on histamine release. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack
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include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Pantetheine: An intermediate in the pathway of coenzyme A formation in mammalian liver and some microorganisms. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentosan polysulfate: A drug used to relieve pain or discomfort associated with chronic inflammation of the bladder. It is also being evaluated for its protective effects on the gastrointestinal tract in people undergoing radiation therapy. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the
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principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Peroral: Performed through or administered through the mouth. [EU] Perphenazine: An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] 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] Phenazopyridine: A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity. [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] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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]
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Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphoric Acids: Inorganic derivatives of phosphoric acid (H3PO4). Inorganic salts are known as phosphates and organic esters are phosphoric acid esters. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GABA-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Piroxicam:
4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide
1,1-
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dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH]
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Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Portal Pressure: The venous pressure measured in the portal vein. [NIH] Post partum: After childbirth, or after delivery. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government
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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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] 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] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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
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fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promazine: A phenothiazine with actions similar to chlorpromazine but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic. [NIH] Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [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] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [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] Protective Agents: Synthetic or natural substances which are given to prevent a disease or
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disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein 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] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [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] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychological Tests: Standardized tests designed to measure abilities, as in intelligence, aptitude, and achievement tests, or to evaluate personality traits. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychomotor Performance: The coordination of a sensory or ideational (cognitive) process and a motor activity. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]
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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 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 Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Punctures: Incision of tissues for injection of medication or for other diagnostic or therapeutic procedures. Punctures of the skin, for example may be used for diagnostic drainage; of blood vessels for diagnostic imaging procedures. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyridostigmine Bromide: A cholinesterase inhibitor with a slightly longer duration of action than neostigmine. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita,
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because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] 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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor
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cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [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] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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 Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retrobulbar: Behind the pons. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH]
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Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritanserin: A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rolipram: A phosphodiesterase inhibitor with antidepressant properties. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saccharin: Flavoring agent and non-nutritive sweetener. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [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]
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Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] 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] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH]
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Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [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
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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] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Soman: An organophosphorus compound that inhibits cholinesterase. It causes seizures and has been used as a chemical warfare agent. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Sonogram: A computer picture of areas inside the body created by bouncing sound waves off organs and other tissues. Also called ultrasonogram or ultrasound. [NIH] 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] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH]
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Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] 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] 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] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU]
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Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
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] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [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] Symphysis: A secondary cartilaginous joint. [NIH] 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] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin
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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 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] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [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]
Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart
Dictionary 231
and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tiapride: Benzamide derivative with dopamine antagonist actions similar to sulpiride. It has been used as an antipsychotic and in the treatment of various movement disorders. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tocainide: An antiarrhythmic agent which exerts a potential- and frequency-dependent block of sodium channels. [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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH]
232 Diazepam
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] Toxicologic: Pertaining to toxicology. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Traction: The act of pulling. [NIH] Tranquillizer: A drug with a calming, soothing effect. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection of the prostate: Surgical procedure to remove tissue from the prostate using an instrument inserted through the urethra. Also called TURP. [NIH] Transvaginal ultrasound: A procedure used to examine the vagina, uterus, fallopian tubes, and bladder. An instrument is inserted into the vagina, and sound waves bounce off organs inside the pelvic area. These sound waves create echoes, which a computer uses to create a picture called a sonogram. Also called TVS. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some
Dictionary 233
Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
234 Diazepam
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Headaches: A group of disorders characterized by recurrent headaches associated with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the
Dictionary 235
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] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [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]
236 Diazepam
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] Xylazine: An adrenergic alpha-agonist used as a sedative, analgesic, and muscle relaxant in veterinary medicine. [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]
237
INDEX A Abdomen, 163, 173, 203, 212, 228, 235 Abdominal, 118, 163, 179, 212, 213 Abdominal Pain, 118, 163 Acatalasia, 163, 175 Acceptor, 163, 212, 232 Acepromazine, 74, 75, 163 Acetaldehyde, 163, 185 Acetaminophen, 101, 163 Acetic Acids, 115, 163 Acetylcholine, 76, 89, 163, 177 Acoustic, 47, 80, 83, 85, 86, 89, 163, 235 Acrylonitrile, 163, 224 Acuity, 163, 170 Acute lymphoblastic leukemia, 55, 163 Acute lymphocytic leukemia, 163 Acyl, 28, 52, 58, 102, 107, 108, 119, 120, 163 Adaptation, 163, 176, 216 Adenine, 164 Adenocarcinoma, 31, 92, 164, 196 Adenosine, 108, 164, 215, 231 Adenovirus, 11, 164 Adenylate Cyclase, 164, 192 Adjuvant, 40, 164 Adolescence, 5, 35, 164 Adrenal Cortex, 164, 181, 182, 218, 223 Adrenergic, 164, 166, 167, 169, 170, 185, 186, 188, 219, 221, 229, 236 Adverse Effect, 9, 11, 164, 169, 178, 201, 226 Aerobic, 164, 206 Aerosol, 89, 119, 164, 210, 229 Afferent, 164, 190, 218 Affinity, 7, 45, 103, 116, 164, 178, 202, 226 Agonist, 7, 10, 16, 25, 50, 91, 111, 164, 169, 171, 172, 173, 174, 185, 198, 207, 208, 210, 236 Agoraphobia, 164, 198, 213, 215 Airway, 165, 173 Akathisia, 52, 165, 169 Albumin, 165, 216 Albuminuria, 165, 218 Alcohol Drinking, 7, 165 Aldehyde Dehydrogenase, 165, 185 Alertness, 33, 48, 165 Alfentanil, 31, 65, 165 Algorithms, 165, 172 Alimentary, 165, 200, 213, 214
Alkaline, 117, 165, 166, 173, 212, 214 Alkaloid, 165, 170, 172, 178, 207, 210, 221, 225, 230 Alleles, 165, 196 Allergen, 165, 225 Allylamine, 165, 166 Alpha-1, 14, 165, 166 Alternative medicine, 131, 165 Alveoli, 166, 234 Amebiasis, 166, 206 Ameliorating, 101, 166 Amine, 111, 166, 196 Amino Acid Motifs, 166, 180 Amino Acid Sequence, 108, 120, 166, 168, 180, 193 Amino Acids, 166, 169, 180, 189, 190, 193, 209, 214, 217, 220, 224, 232, 233 Amitriptyline, 123, 166 Ammonia, 75, 166, 194, 229, 233 Amnesia, 27, 45, 166 Amnestic, 166, 192, 206 Amphetamine, 5, 15, 148, 166, 184 Ampulla, 166, 188, 190 Amygdala, 6, 20, 21, 27, 166, 171, 202, 230 Anaesthesia, 32, 34, 37, 51, 59, 65, 67, 69, 74, 79, 90, 91, 92, 122, 166, 199 Anal, 46, 167, 191 Analog, 106, 167, 172 Analogous, 167, 232 Anatomical, 6, 12, 167, 170, 173, 199, 225 Anemia, 145, 167, 204 Anesthesia, 29, 38, 48, 50, 55, 62, 74, 89, 92, 109, 110, 165, 167, 180, 182, 187, 201, 205, 206, 218 Anesthetics, 109, 110, 124, 167, 171, 188, 194 Aneuploidy, 40, 167 Angina, 167, 210, 219 Angina Pectoris, 167, 219 Anginal, 167, 210 Animal model, 6, 12, 18, 20, 167 Anions, 165, 167, 201, 226, 229 Antagonism, 8, 91, 167, 178, 184, 186, 231 Antiallergic, 167, 182, 219 Anti-Anxiety Agents, 167, 218 Antiarrhythmic, 167, 206, 231 Antibacterial, 167, 201, 227 Antibiotic, 167, 168, 189, 209, 213, 218, 227
238 Diazepam
Antibiotic Prophylaxis, 168, 218 Antibodies, 102, 103, 106, 108, 109, 120, 168, 195, 198, 203, 207, 216 Antibody, 106, 164, 168, 179, 182, 195, 196, 198, 199, 204, 207, 222, 225, 227 Anticholinergic, 9, 124, 166, 168, 176, 186, 215 Anticoagulant, 168, 220, 236 Anticonvulsant, 25, 60, 76, 90, 93, 168, 174, 176, 178, 203, 205, 206, 210, 234 Antidepressant, 59, 101, 166, 168, 177, 192, 198, 224, 234 Antidiuretic, 68, 168 Antidote, 113, 168, 191, 215 Antiemetic, 168, 169, 176, 185, 197, 205, 219 Antiepileptic, 22, 168 Antifungal, 168, 201 Antigen, 106, 164, 168, 179, 196, 197, 198, 199, 204, 222, 225 Antihistamine, 118, 168 Antihypertensive, 101, 168, 192 Anti-inflammatory, 6, 100, 163, 168, 170, 182, 184, 194, 198, 199, 201, 204, 216, 224 Anti-Inflammatory Agents, 168, 170, 182 Antimetabolite, 168, 184 Antimycotic, 69, 168 Antipsychotic, 12, 61, 68, 103, 168, 176, 178, 209, 214, 219, 231 Antipyretic, 163, 169, 184, 201, 204, 221 Antispasmodic, 169, 194, 211, 225 Antitussive, 169, 185, 211 Antiviral, 6, 169, 184 Anus, 59, 167, 169, 173, 200, 222 Anxiety Disorders, 6, 21, 25, 119, 169, 213 Anxiolytic, 6, 9, 20, 21, 22, 25, 62, 68, 80, 83, 87, 91, 105, 169, 173, 176, 192, 206 Aorta, 169, 181, 235 Apathy, 169, 209 Apomorphine, 84, 169 Aptitude, 169, 220 Aqueous, 169, 171, 187, 197 Arachidonic Acid, 169, 219 Arginine, 75, 124, 169 Arrhythmia, 167, 169, 191, 235 Arterial, 34, 46, 165, 169, 174, 181, 197, 210, 220, 230 Arteries, 169, 172, 173, 181, 206, 208, 221 Arterioles, 169, 173, 174, 206 Articular, 37, 169, 212 Aspartate, 169, 201, 214 Aspartic, 103, 169, 190
Aspartic Acid, 103, 169 Aspergillosis, 169, 201 Asphyxia, 170, 210 Aspirin, 101, 149, 170 Assay, 4, 102, 106, 109, 115, 116, 170, 198, 222 Astrocytoma, 170, 193 Asymptomatic, 163, 166, 170, 191 Ataxia, 144, 145, 170, 198, 230 Atenolol, 86, 170 Atmospheric Pressure, 170, 197 Atrial, 65, 170, 181, 191, 233, 236 Atrial Fibrillation, 170, 236 Atrioventricular, 170, 181 Atrium, 170, 181, 233, 235 Atrophy, 144, 149, 170 Atropine, 29, 59, 72, 122, 124, 170, 171, 225 Atypical, 12, 170, 178, 210 Audiometry, 80, 170 Auditory, 47, 50, 85, 91, 92, 170, 189, 197, 218 Autacoids, 170, 199 Autogenic, 13, 170 Autonomic, 66, 163, 169, 170, 171, 210 Autoradiography, 7, 171 Axons, 171, 184, 200, 218, 221 B Babesiosis, 171, 221 Baclofen, 18, 47, 70, 81, 85, 149, 171 Bacteria, 64, 163, 167, 168, 171, 183, 187, 190, 206, 227, 232, 234 Bactericidal, 171, 189 Bacteriostatic, 171, 189 Barbital, 82, 171 Barbiturate, 26, 171 Basal Ganglia, 13, 104, 105, 169, 170, 171, 177, 193, 202, 211 Basal Ganglia Diseases, 170, 171, 177 Base, 19, 164, 171, 183, 193, 201, 214, 217, 221, 230 Belladonna, 170, 171 Benactyzine, 113, 171 Benign, 171, 195, 209 Benzene, 171, 172 Benzoic Acid, 124, 172 Betahistine, 149, 172 Bicuculline, 16, 172 Bifida, 172 Bile, 172, 192, 197, 203, 228 Binding Sites, 66, 103, 115, 116, 172 Bioavailability, 54, 172
Index 239
Biochemical, 23, 33, 65, 66, 68, 165, 168, 172, 194, 212, 225 Biosynthesis, 28, 169, 172, 192, 233 Biotechnology, 26, 28, 122, 131, 141, 143, 144, 145, 172 Bladder, 123, 172, 182, 199, 209, 213, 219, 232, 233, 234 Blastocyst, 172, 216 Blastomycosis, 172, 201 Blood Coagulation, 172, 173 Blood Platelets, 172, 225 Blood pressure, 18, 100, 101, 168, 172, 174, 176, 197, 198, 207, 210, 221, 227 Blood-Brain Barrier, 6, 173, 209, 215 Body Fluids, 106, 173, 227 Body Regions, 173, 179 Bolus, 71, 173 Bolus infusion, 173 Bone Conduction, 170, 173 Bone Marrow, 55, 163, 171, 173, 198, 203 Bowel, 167, 173, 180 Bowel Movement, 173, 180 Bradykinin, 173, 216 Branch, 157, 173, 187, 193, 203, 213, 227, 231 Breakdown, 103, 173, 184, 192 Bronchial, 172, 173, 196, 219, 231 Bronchodilator, 101, 173 Bupivacaine, 84, 173, 202 Buspirone, 6, 33, 36, 38, 50, 53, 61, 74, 80, 81, 88, 173 Butorphanol, 74, 75, 173 Butyric Acid, 13, 24, 26, 111, 173 C Calcium, 19, 43, 44, 112, 124, 173, 174, 179, 185, 210, 226, 235 Calcium channel blocker, 112, 124, 174, 235 Calcium Channel Blockers, 124, 174 Capillary, 59, 67, 173, 174, 235 Capsules, 117, 174 Captopril, 112, 174 Carbachol, 62, 174 Carbamazepine, 33, 35, 74, 124, 149, 174 Carbohydrate, 118, 174, 181, 194, 217 Carbon Dioxide, 174, 183, 191, 192, 216, 223 Carboxy, 104, 174 Carcinogen, 174, 206 Carcinogenic, 171, 174, 200, 219, 228 Carcinoma, 174
Cardiac, 53, 63, 65, 80, 88, 101, 165, 167, 170, 174, 177, 181, 188, 190, 202, 206, 208, 221, 223, 228 Cardiac arrest, 63, 80, 88, 174 Cardiopulmonary, 3, 174 Cardiorespiratory, 74, 75, 174, 206 Cardioselective, 170, 174, 219 Cardiovascular, 84, 166, 174, 189, 225 Cardiovascular System, 174, 189 Cardioversion, 65, 174 Carrier Proteins, 174, 216, 222 Case report, 175, 178 Case series, 175, 178 Catalase, 11, 163, 175 Catecholamine, 175, 185 Catheters, 24, 175 Cations, 175, 201 Caudal, 175, 184, 198, 211, 217 Caudate Nucleus, 171, 175, 211 Cell Cycle, 175, 189 Cell Differentiation, 175, 226 Cell Division, 144, 171, 175, 189, 204, 206, 216, 219 Cell membrane, 174, 175, 184, 213, 227 Cell proliferation, 175, 226 Cell Respiration, 175, 206, 223 Central Nervous System Infections, 175, 195 Centrifugation, 176, 206 Cerebellar, 51, 170, 176, 222, 233 Cerebellum, 176, 217, 222 Cerebral hemispheres, 171, 176, 193, 230 Cerebrospinal, 36, 109, 176 Cerebrospinal fluid, 36, 109, 176 Cerebrovascular, 43, 171, 174, 176, 210, 230 Cerebrum, 176, 215, 230, 233 Cetirizine, 176, 197 Chemical Warfare, 176, 227 Chemokines, 7, 176 Chemoreceptor, 169, 176 Chemotherapy, 44, 176, 185 Chlordiazepoxide, 14, 55, 102, 108, 109, 111, 116, 117, 121, 176 Chlorpromazine, 84, 176, 214, 219 Cholecystokinin, 27, 103, 104, 176 Cholesterol, 28, 41, 172, 176, 228 Cholinergic, 166, 169, 171, 174, 177, 210 Chondroitin sulfate, 123, 177 Chorea, 168, 177 Chromatin, 177, 228 Chromosomal, 17, 58, 167, 177
240 Diazepam
Chromosome, 167, 177, 196, 207, 233 Chronic renal, 177, 217 Ciliary, 53, 177 Cimetidine, 123, 177 Cinchona, 177, 221 Circadian, 13, 177 Circadian Rhythm, 13, 177 Circulatory system, 177, 188, 212 CIS, 39, 177 Citalopram, 46, 177 Clamp, 13, 26, 177, 213 Clinical study, 92, 177 Clinical trial, 4, 54, 63, 141, 178, 181, 220, 222 Clonazepam, 75, 76, 85, 93, 124, 149, 178 Clonic, 178, 205 Cloning, 17, 27, 28, 37, 58, 172, 178 Clopenthixol, 39, 178 Clozapine, 71, 178 Coagulation, 172, 178, 195, 216, 236 Coca, 178 Cocaine, 19, 63, 103, 104, 112, 148, 178 Cochlear, 178, 197, 231, 235 Cochlear Diseases, 178, 231 Cod Liver Oil, 178, 187 Codeine, 148, 178, 211 Coenzyme, 108, 120, 178, 213 Cofactor, 178, 220 Cognition, 26, 179, 209 Colic, 118, 179 Collagen, 179, 216, 219 Collapse, 173, 179 Colloidal, 165, 179, 187, 214, 226, 229 Colonoscopy, 29, 57, 76, 179 Complement, 179, 193, 216, 225 Complementary and alternative medicine, 79, 96, 179 Complementary medicine, 79, 179 Computational Biology, 141, 143, 180 Conduction, 170, 180 Confounding, 20, 180 Confusion, 180, 185, 198, 209 Congenita, 180, 221 Congestion, 169, 180, 188 Conjugated, 106, 172, 180, 182 Conjunctiva, 180, 215 Connective Tissue, 173, 179, 180, 191, 192, 224 Conscious Sedation, 29, 31, 32, 37, 50, 57, 70, 76, 180 Consciousness, 165, 167, 180, 183, 185, 188, 223, 228, 230
Consensus Sequence, 7, 166, 180 Conserved Sequence, 166, 180 Constipation, 169, 180 Constriction, 180, 201, 234 Consumption, 21, 180, 212 Contact dermatitis, 68, 180 Continence, 46, 180 Contraindications, ii, 180 Contralateral, 180, 205, 211, 222 Control group, 107, 181 Controlled study, 46, 72, 79, 181 Convulsions, 26, 39, 48, 60, 70, 75, 76, 81, 122, 159, 168, 171, 172, 181, 186, 198 Convulsive, 29, 37, 39, 181 Coordination, 176, 181, 220 Cor, 36, 181, 182 Corneum, 83, 181, 188 Coronary, 51, 63, 67, 167, 181, 206, 208, 210 Coronary Artery Bypass, 67, 181 Coronary Thrombosis, 181, 206, 208 Cortex, 18, 116, 170, 181, 188, 189, 191, 218, 221, 223 Cortical, 68, 85, 116, 181, 190, 218, 221, 225, 230 Corticosteroid, 181, 218 Corticotropin-Releasing Hormone, 36, 182 Cortisol, 24, 165, 182 Cranial, 176, 182, 190, 195, 200, 211, 235 Craniocerebral Trauma, 171, 182, 195, 230, 231 Cromolyn Sodium, 123, 182 Cryoprotective, 112, 113, 182 Cultured cells, 24, 182 Curare, 182, 207, 212 Curative, 182, 210, 231 Cutaneous, 68, 172, 180, 182 Cyanide, 182, 205 Cyclic, 40, 164, 182, 192, 215, 231 Cysteine, 19, 176, 182 Cystine, 182 Cystitis, 123, 148, 182 Cytochrome, 52, 57, 66, 177, 182 Cytokines, 7, 176, 182 Cytotoxic, 183, 226 Cytotoxicity, 41, 82, 165, 183 D Databases, Bibliographic, 141, 183 Deamination, 183, 233 Decarboxylation, 183, 196, 207 Decidua, 183, 206, 216 Degenerative, 183, 207, 212
Index 241
Deletion, 20, 183 Delirium, 34, 168, 183 Dementia, 6, 48, 168, 183 Dendrites, 183, 184, 209, 221 Density, 41, 176, 183, 211, 227 Dental Care, 33, 183 Dental Caries, 183, 191, 227 Dentate Gyrus, 16, 184, 196 Deoxyglucose, 10, 184 Depersonalization, 184, 213, 224 Depolarization, 184, 226 Derealization, 184, 213 Dermatitis, 184, 197 Detoxification, 107, 184 Dextroamphetamine, 97, 166, 184, 205 Diagnostic Imaging, 184, 221 Diagnostic procedure, 99, 131, 184 Diastolic, 184, 197 Diclofenac, 48, 84, 100, 184 Diclofenac Sodium, 184 Diencephalon, 184, 198, 218, 230, 231 Diffusion, 83, 184, 199 Digestion, 19, 165, 172, 173, 184, 203, 214, 228 Digestive tract, 184, 189, 226 Dilatation, 184, 218, 234 Dilator, 184, 210 Diltiazem, 47, 112, 184 Dimenhydrinate, 124, 185 Diphenhydramine, 124, 185 Diploid, 167, 185, 207, 216, 233 Direct, iii, 7, 9, 16, 20, 45, 133, 174, 185, 193, 222, 223 Discrimination, 14, 36, 185 Disinfectant, 185, 189 Disorientation, 180, 183, 185 Disposition, 19, 42, 47, 49, 58, 65, 69, 185 Dissociation, 83, 127, 164, 185, 201 Dissociative Disorders, 185 Distal, 181, 185, 218 Disulfiram, 107, 185 Dizziness, 12, 160, 185, 213, 235 Dopamine, 13, 15, 19, 75, 166, 169, 176, 178, 184, 185, 205, 207, 215, 231 Dorsal, 20, 85, 185, 217 Dorsum, 185, 186 Dose-dependent, 14, 186 Doxepin, 101, 186 Drug Delivery Systems, 22, 186 Drug Evaluation, 14, 124, 186 Drug Interactions, 65, 134, 186 Drug Tolerance, 186, 231
Duodenum, 172, 186, 188, 192, 228 Dyes, 19, 186 Dyskinesia, 169, 177, 186 Dysmenorrhea, 186, 216 Dysplasia, 145, 186 Dyspnea, 186, 213 Dystonia, 169, 186 Dystrophy, 144, 186 E Eclampsia, 42, 56, 186 Edema, 118, 180, 186, 200, 211 Effector, 163, 179, 186, 210, 215 Efficacy, 5, 14, 18, 26, 34, 48, 74, 117, 173, 186 Elasticity, 25, 186 Elective, 65, 187 Electroacupuncture, 83, 84, 88, 187 Electrolyte, 181, 183, 187, 217, 227 Electrons, 171, 187, 201, 212, 222 Electrophoresis, 59, 187 Electrophysiological, 13, 20, 187 Emboli, 187, 236 Embolism, 187, 221, 236 Embolization, 187, 236 Embryo, 172, 175, 187, 199 Emergency Medicine, 37, 62, 63, 67, 70, 187 Emergency Treatment, 37, 130, 187 Emetic, 169, 187 Emulsion, 57, 76, 114, 171, 187, 191 Enalapril, 112, 187 Encephalopathy, 49, 187 Endemic, 187, 204, 228 Endocrine Glands, 104, 105, 188 Endocrine System, 188, 209 Endometrium, 183, 188, 206 Endoscope, 188, 189 Endoscopic, 3, 32, 179, 188, 206 Endoscopy, 3, 29, 30, 50, 57, 60, 65, 188 Endothelial cell, 173, 188 End-stage renal, 177, 188, 217 Enkephalin, 6, 188 Entorhinal Cortex, 188, 196 Environmental Exposure, 188, 211 Environmental Health, 140, 142, 188 Enzymatic, 173, 179, 183, 188, 196 Enzyme Inhibitors, 188, 216 Epidemiological, 15, 188 Epidermal, 83, 188, 204 Epidermis, 181, 188, 201 Epilepticus, 16, 26, 188 Epinephrine, 164, 185, 188, 210, 233
242 Diazepam
Epithelial, 164, 183, 188, 196 Epithelial Cells, 188, 196 Erythema, 180, 188, 234 Erythrocytes, 116, 167, 171, 173, 189, 225 Erythromycin, 54, 189 Esophagogastroduodenoscopy, 46, 189 Esophagus, 184, 189, 228 Esotropia, 189, 228 Essential Tremor, 144, 189 Estrogen, 189, 218 Ethanol, 5, 7, 8, 10, 11, 15, 17, 21, 51, 62, 74, 177, 189 Ethanolamine, 101, 189 Ethnic Groups, 19, 189 Etomidate, 47, 189 Etoposide, 41, 82, 189 Eukaryotic Cells, 189, 199, 211 Evacuation, 180, 189, 192 Evoke, 189, 228 Evoked Potentials, 85, 189 Excitability, 190, 208, 221 Excitation, 81, 176, 190 Excitatory, 13, 109, 171, 190, 194, 198 Excitatory Amino Acids, 13, 190 Exhaustion, 167, 190, 204 Exocrine, 176, 190, 212 Exogenous, 13, 174, 190, 194, 220 Exotropia, 190, 228 Expiration, 190, 223 Extracellular, 180, 190, 227 Extraction, 18, 116, 190 Extrapyramidal, 165, 169, 185, 190 Eye Infections, 164, 190 F Facial, 27, 110, 190, 197 Facial Nerve, 190, 197 Facial Nerve Diseases, 190, 197 Fallopian Tubes, 190, 232, 233 Family Planning, 141, 190 Fat, 169, 173, 181, 187, 190, 202, 224, 225, 227, 229 Fathers, 46, 190 Fatigue, 115, 191, 195 Fatty acids, 165, 191, 219 Febrile, 27, 38, 43, 54, 62, 191, 204 Fentanyl, 19, 37, 50, 51, 69, 85, 124, 165, 191 Ferrets, 74, 75, 191 Fetus, 191, 216, 218, 234 Fibrinogen, 191, 216 Fibrosis, 145, 165, 191, 225 Fissure, 184, 191, 218
Fixation, 191, 225 Flatus, 191, 192 Flecainide, 149, 191 Flumazenil, 9, 14, 50, 55, 57, 58, 76, 191 Flunitrazepam, 19, 54, 115, 191 Fluorine, 67, 191 Fluoxetine, 59, 72, 192 Flurazepam, 111, 115, 116, 148, 192 Flushing, 185, 192 Fluvoxamine, 38, 74, 81, 192 Fold, 25, 191, 192 Forearm, 172, 192 Forskolin, 42, 192 Fosinopril, 112, 192 Frontal Lobe, 192, 218 Fructose, 192, 201 Fungi, 168, 169, 190, 192, 206, 236 Fungistatic, 172, 192 G Gallbladder, 163, 176, 192 Gamma-hydroxybutyrate, 81, 192 Ganglia, 13, 163, 171, 192, 209 Gas, 51, 67, 106, 113, 115, 116, 166, 174, 184, 189, 191, 192, 197, 210, 229, 234 Gas exchange, 192, 234 Gastric, 8, 46, 75, 76, 87, 104, 117, 160, 177, 192, 196, 214 Gastric Acid, 104, 177, 192 Gastric Emptying, 76, 192 Gastrin, 104, 177, 192, 196 Gastrointestinal tract, 36, 104, 105, 117, 189, 192, 194, 213, 225 Gene, 6, 7, 11, 13, 17, 28, 31, 46, 52, 122, 145, 146, 164, 165, 172, 193, 201, 211, 216 Gene Dosage, 46, 193 Gene Expression, 13, 145, 193 General practitioner, 125, 193 Genetic Code, 193, 211 Genetic Counseling, 149, 193 Genetic Engineering, 172, 178, 193 Genotype, 47, 193, 214 Germ Cells, 193, 204, 227, 228 Gestation, 193, 216 Giardiasis, 193, 206 Ginkgo biloba, 83, 88, 94, 193 Ginseng, 84, 95, 193 Glafenine, 101, 193 Gland, 27, 87, 164, 193, 212, 216, 219, 225, 228, 229, 231 Glioblastoma, 60, 61, 193 Glioblastoma multiforme, 60, 193 Glioma, 28, 41, 82, 193
Index 243
Glomerular, 193, 201, 223 Glucocorticoid, 194, 206, 218 Glucose, 15, 98, 144, 184, 194, 195, 198, 200 Glutamate, 10, 21, 27, 194, 214 Glutamic Acid, 103, 194, 219 Glutamine, 86, 111, 194 Glycerol, 173, 194 Glycine, 172, 194 Glycopyrrolate, 74, 194 Glycosaminoglycan, 177, 194 Glycosylation, 23, 194 Governing Board, 194, 218 Government Agencies, 25, 194, 218 Grade, 193, 194 Graft, 67, 194, 197 Grafting, 181, 194 Granule, 16, 26, 51, 184, 194, 224 Granulocytes, 194, 202, 226, 236 Gravis, 194, 209, 221 Growth, 19, 53, 103, 144, 164, 167, 168, 171, 175, 192, 194, 204, 209, 211, 216, 231, 233 Growth Inhibitors, 103, 194 H Habitat, 195, 210 Habituation, 86, 195 Half-Life, 3, 195, 216 Hallucinogen, 195, 214 Haloperidol, 84, 195 Haptens, 102, 106, 109, 164, 195, 222 Head Movements, 11, 195 Headache, 48, 86, 195, 198, 234 Headache Disorders, 195 Heart failure, 195, 202, 211 Heme, 182, 195 Hemoglobin, 167, 189, 195 Hemoglobinuria, 144, 195 Hemorrhage, 182, 195, 228 Hemostasis, 195, 225 Hepatic, 74, 165, 183, 195, 203 Hepatocellular, 41, 196 Hepatocellular carcinoma, 41, 196 Hepatocytes, 112, 196 Hereditary, 149, 196, 207, 216, 223 Heredity, 193, 196 Herpes, 6, 196 Herpes virus, 6, 196 Herpes Zoster, 196 Heterogeneity, 164, 196 Heterotropia, 196, 228 Heterotropic, 34, 196 Heterozygote, 21, 196 Hiccup, 176, 196
Hippocampus, 12, 21, 26, 76, 184, 196, 202, 221, 229 Histamine, 168, 169, 172, 176, 177, 185, 186, 196, 197, 204, 212, 219 Histamine Release, 196, 212 Homeostasis, 103, 196 Homogeneous, 109, 196 Homologous, 165, 196, 225, 229, 230 Hormonal, 31, 170, 181, 196 Hormone, 11, 27, 28, 61, 68, 104, 105, 177, 181, 182, 188, 192, 196, 200, 205, 206, 218, 224, 226, 230, 231 Host, 107, 119, 171, 197, 198, 235 Humoral, 13, 197 Humour, 197 Hydrogel, 22, 197 Hydrogen, 163, 166, 171, 174, 175, 197, 207, 212, 220, 229 Hydrogen Peroxide, 175, 197, 229 Hydrolysis, 169, 197, 215, 217, 220 Hydrophilic, 108, 197 Hydroxylation, 39, 197, 233 Hydroxyzine, 89, 118, 123, 197 Hyperacusis, 85, 190, 197 Hyperbaric, 81, 92, 197 Hyperbaric oxygen, 81, 92, 197 Hyperemesis, 49, 197 Hypersecretion, 104, 197 Hypersensitivity, 52, 165, 185, 197, 224, 225 Hypertension, 111, 112, 174, 187, 192, 197, 200, 202, 218, 219 Hyperthyroidism, 197, 219 Hypertrophy, 181, 197, 233 Hypnotic, 8, 9, 14, 18, 25, 87, 110, 114, 118, 171, 185, 189, 192, 197, 203, 206, 210 Hypoglycaemia, 183, 198 Hypotension, 169, 181, 185, 198 Hypothalamus, 13, 15, 182, 184, 188, 198, 202, 216, 229, 231 Hypoxia, 183, 198, 230 I Ibotenic Acid, 198, 207 Ibuprofen, 30, 46, 70, 92, 101, 198, 201 Id, 77, 93, 150, 156, 158, 198 Illusion, 198, 235 Imaging procedures, 198, 232 Imipramine, 49, 59, 80, 198 Immune function, 85, 198 Immune response, 164, 168, 182, 195, 198, 225, 229, 235
244 Diazepam
Immune system, 198, 199, 203, 208, 234, 236 Immunity, 198 Immunization, 198, 225 Immunoassay, 102, 108, 109, 198 Immunodeficiency, 27, 44, 144, 198 Immunogen, 102, 108, 109, 198 Immunogenic, 108, 109, 198, 222 Immunoglobulin, 168, 198, 207 Immunohistochemistry, 6, 10, 198 Immunologic, 198 Immunology, 164, 199 Impairment, 4, 9, 16, 50, 65, 105, 170, 183, 186, 190, 199, 221 In situ, 10, 199 In Situ Hybridization, 10, 199 In vitro, 9, 11, 14, 25, 44, 47, 52, 53, 65, 85, 87, 88, 199 In vivo, 11, 14, 58, 65, 199 Incision, 199, 201, 221 Incontinence, 199, 225 Incubated, 7, 199 Incubator, 113, 199 Indicative, 121, 199, 213, 234 Indomethacin, 101, 199 Induction, 16, 53, 168, 189, 199, 201, 205, 218, 222 Infarction, 199 Infection, 6, 166, 172, 177, 183, 190, 193, 198, 199, 203, 209, 213, 224, 229, 233, 234, 236 Infiltration, 32, 110, 199, 218 Inflammation, 52, 101, 165, 168, 170, 177, 180, 182, 184, 190, 191, 196, 199, 205, 213, 224, 234 Infusion, 35, 39, 64, 200 Ingestion, 100, 200, 217 Inhalation, 5, 89, 109, 119, 164, 196, 200, 217 Initiation, 200, 203 Inlay, 200, 223 Innervation, 186, 190, 200 Inorganic, 200, 215, 227 Inotropic, 170, 185, 200 Inpatients, 70, 200 Insecticides, 200, 214 Insomnia, 18, 94, 116, 118, 200, 212, 233 Insulin, 98, 108, 120, 200 Insulin-dependent diabetes mellitus, 200 Interneurons, 16, 200 Interstitial, 123, 148, 200, 223 Intestinal, 64, 75, 87, 113, 176, 200, 203
Intestines, 117, 163, 192, 200, 225 Intoxication, 58, 80, 183, 200, 236 Intracellular, 43, 44, 92, 174, 199, 200, 205, 217, 222, 226 Intracranial Hypertension, 195, 200, 231 Intramuscular, 31, 32, 37, 89, 200, 213 Intraocular, 111, 192, 200, 211 Intraocular pressure, 111, 192, 200, 211 Intravenous Anesthetics, 109, 200 Intrinsic, 164, 201 Inulin, 74, 201 Invasive, 91, 123, 198, 201 Involuntary, 171, 177, 189, 195, 201, 208, 223, 227 Ionization, 51, 201 Ions, 8, 171, 185, 187, 197, 201, 227 Irrigation, 41, 201 Ischemia, 53, 98, 167, 170, 201 Isoniazid, 76, 201 Isopropyl, 113, 201 Itraconazole, 69, 201 J Joint, 169, 201, 212, 229 K Kava, 80, 95, 201 Kb, 140, 201 Keratin, 201, 225 Ketamine, 30, 32, 34, 48, 55, 69, 70, 74, 92, 100, 109, 110, 127, 201, 214 Ketoprofen, 102, 201 Kidney Disease, 140, 145, 165, 201 Kinetic, 17, 24, 34, 58, 66, 201 L Lactation, 202, 218 Large Intestine, 184, 200, 202, 222, 226 Laryngeal, 74, 202 Larynx, 202 Lavage, 46, 160, 202 Lesion, 172, 181, 202, 203, 230 Lethal, 39, 171, 182, 202 Leucocyte, 165, 202, 203 Leukemia, 87, 144, 202 Leukocytes, 173, 176, 182, 194, 199, 202 Levo, 109, 202 Library Services, 156, 202 Lidocaine, 29, 37, 202, 206 Ligament, 202, 219 Ligands, 7, 23, 25, 103, 106, 108, 202 Ligation, 202 Limbic, 85, 166, 202, 218 Limbic System, 166, 202, 218 Lipid, 57, 75, 76, 194, 200, 202, 206
Index 245
Lipophilic, 25, 202 Lisinopril, 112, 202 Lithium, 168, 202 Liver, 11, 43, 44, 49, 52, 53, 57, 74, 101, 108, 120, 163, 165, 169, 172, 187, 192, 195, 196, 203, 213, 223, 233 Liver Cirrhosis, 49, 203 Liver Neoplasms, 49, 203 Loading dose, 34, 203 Loc, 101, 203 Localization, 12, 36, 50, 58, 87, 198, 203 Localized, 183, 191, 199, 203, 211, 216, 234 Locomotion, 18, 203, 216 Locomotor, 13, 86, 203 Loop, 149, 203 Lorazepam, 9, 14, 29, 37, 45, 56, 62, 66, 70, 79, 89, 91, 124, 134, 203 Luteal Phase, 203, 206 Lutein Cells, 203, 218 Lymph, 76, 177, 188, 197, 203 Lymphatic, 199, 203, 211 Lymphatic system, 203 Lymphoblastic, 203 Lymphoblasts, 163, 203 Lymphocyte, 168, 203, 204 Lymphoid, 87, 168, 202, 203 Lymphoma, 144, 203 M Malabsorption, 144, 203 Malaria, 51, 60, 177, 204 Malaria, Falciparum, 204 Malaria, Vivax, 204 Malignant, 44, 59, 144, 164, 193, 204, 209 Malnutrition, 165, 170, 204, 208 Mammary, 92, 181, 204 Manic, 168, 203, 204, 221 Manifest, 204, 228 Meclizine, 11, 124, 204 Medial, 12, 190, 204, 211 Mediate, 8, 27, 185, 204 Mediator, 176, 204, 225 Medical Records, 204, 223 Medicament, 117, 118, 204 MEDLINE, 141, 143, 145, 204 Mefenamic Acid, 81, 204 Meiosis, 204, 230 Melanin, 204, 215, 233 Melanocytes, 204, 205 Melanoma, 144, 205 Membrane Proteins, 205, 220 Memory, 9, 16, 33, 39, 41, 45, 48, 55, 70, 87, 89, 98, 166, 183, 205
Meninges, 175, 182, 205 Meningitis, 94, 201, 205 Menopause, 205, 219 Mental Health, iv, 4, 25, 140, 142, 205 Mental Processes, 185, 205, 220 Meperidine, 30, 36, 37, 59, 65, 205 Mephenytoin, 39, 69, 205 Mesencephalic, 85, 205, 222 Mesolimbic, 169, 205 Meta-Analysis, 70, 205 Metabolite, 108, 109, 111, 116, 192, 197, 205, 210, 218 Methamphetamine, 148, 205 Methohexital, 14, 36, 205 Methylene Blue, 124, 205 Methylphenidate, 15, 48, 205 Metoclopramide, 29, 205 Metronidazole, 40, 206 Mexiletine, 149, 206 MI, 48, 54, 104, 161, 206 Microbe, 206, 232 Microbiology, 164, 170, 206 Microcirculation, 203, 206 Microorganism, 178, 206, 235 Micro-organism, 183, 195, 206 Microsomal, 49, 52, 57, 206 Microspheres, 22, 206 Midazolam, 3, 27, 29, 30, 31, 32, 35, 37, 38, 39, 48, 50, 54, 57, 59, 64, 65, 66, 76, 84, 92, 206 Mifepristone, 57, 206 Migration, 42, 43, 118, 206 Mitochondria, 28, 61, 206, 211 Mitosis, 103, 206 Mitotic, 189, 206 Modeling, 25, 34, 66, 206 Modification, 9, 12, 23, 84, 193, 207 Modulator, 14, 207 Molecule, 168, 171, 172, 177, 178, 179, 185, 186, 190, 194, 197, 207, 212, 217, 222, 226, 234 Monitor, 207, 211 Monoamine, 166, 184, 207 Monoclonal, 49, 207, 222 Monoclonal antibodies, 49, 207 Monosomy, 167, 207 Morphine, 5, 25, 40, 53, 75, 89, 91, 148, 169, 178, 205, 207, 208, 211 Motility, 199, 207, 225 Motion Sickness, 11, 124, 185, 204, 207, 208, 219, 225 Motor Activity, 181, 207, 220
246 Diazepam
Motor nerve, 207, 211 Motor Neurons, 149, 207 Movement Disorders, 168, 207, 230, 231 Mucins, 207, 224 Mucosa, 118, 176, 207, 218 Muscimol, 16, 111, 207 Muscle Fibers, 207, 208 Muscle relaxant, 25, 100, 114, 124, 167, 207, 209, 221, 236 Muscle tension, 207, 208 Muscular Atrophy, 144, 208 Muscular Dystrophies, 186, 208 Musculoskeletal System, 208, 211 Mutagenesis, 34, 208 Mutagens, 208 Mutism, 71, 208 Myasthenia, 208, 209, 221 Mydriatic, 208, 225 Myocardial infarction, 86, 181, 206, 208, 219, 236 Myocardium, 167, 206, 208 Myotonia, 208, 221 Myotonic Dystrophy, 144, 208 N Naive, 8, 18, 26, 208 Naloxone, 25, 88, 208 Narcolepsy, 184, 205, 208 Narcosis, 100, 208 Narcotic, 110, 124, 163, 173, 191, 205, 207, 208, 210 Nausea, 72, 110, 124, 168, 169, 185, 204, 208, 213 NCI, 1, 139, 177, 208 Necrosis, 193, 199, 206, 208, 209 Need, 3, 25, 103, 106, 109, 116, 123, 124, 135, 151, 164, 177, 209, 231 Neomycin, 149, 209 Neonatal, 58, 68, 209 Neoplasia, 103, 144, 209 Neoplasm, 209, 233 Neoplastic, 103, 203, 209 Neostigmine, 209, 221 Nephropathy, 201, 209 Nervous System, 7, 8, 21, 24, 83, 84, 103, 104, 105, 109, 116, 144, 163, 164, 166, 171, 175, 176, 178, 184, 189, 192, 193, 194, 204, 205, 207, 209, 210, 214, 215, 217, 218, 225, 229, 230, 231 Neural, 12, 16, 20, 50, 74, 87, 164, 197, 209, 227 Neuroendocrine, 14, 209 Neurogenic, 209, 234
Neuroleptic, 44, 52, 59, 165, 168, 178, 209 Neurologic, 26, 167, 193, 209 Neurology, 16, 23, 24, 26, 39, 48, 56, 61, 63, 64, 65, 71, 72, 209 Neuromuscular, 163, 209, 212 Neuromuscular Junction, 163, 209 Neuronal, 6, 13, 177, 208, 209 Neurons, 13, 15, 26, 149, 178, 183, 184, 190, 192, 200, 207, 209, 210, 221, 230, 235 Neuropathy, 111, 209 Neuropeptide, 21, 182, 209 Neurosis, 210, 215 Neurotransmitters, 166, 186, 190, 209, 210, 218 Neutrophil, 44, 75, 85, 210 Niacin, 210, 233 Niche, 24, 210 Nicotine, 15, 19, 103, 104, 112, 210 Nifedipine, 52, 112, 124, 210 Nimodipine, 149, 210 Nitrazepam, 40, 116, 210 Nitrogen, 165, 166, 191, 194, 210, 233 Nitroglycerin, 63, 210 Nitrous Oxide, 17, 48, 51, 63, 100, 210 Nonverbal Communication, 210, 221 Norepinephrine, 164, 166, 185, 210 Nortriptyline, 31, 210 Nuclear, 7, 67, 171, 187, 189, 193, 202, 209, 210, 222, 230 Nuclei, 166, 187, 190, 193, 202, 206, 211, 216, 220, 235 Nucleic acid, 107, 108, 119, 120, 193, 199, 208, 210, 211 Nucleus, 20, 104, 109, 177, 182, 189, 193, 204, 211, 218, 219, 220, 230, 235 Nucleus Accumbens, 104, 211 O Ocular, 11, 111, 189, 190, 211 Ocular Hypertension, 111, 211 Oculomotor, 11, 205, 211 Oedema, 211, 218 Oncogene, 144, 211 Opacity, 183, 211 Ophthalmic, 111, 211 Opium, 207, 211 Optic Chiasm, 198, 211, 229 Organelles, 176, 204, 211, 213 Orofacial, 30, 211 Orthopaedic, 29, 211 Orthostatic, 169, 212 Osmotic, 165, 212, 226 Osteoarthritis, 79, 94, 201, 212, 216
Index 247
Outpatient, 39, 70, 110, 212 Ovaries, 190, 212, 226, 233 Overdose, 55, 90, 148, 159, 212 Overexpress, 21, 212 Ovum, 183, 193, 212, 218 Oxazepam, 47, 51, 64, 102, 109, 116, 212 Oxidation, 34, 69, 163, 182, 212 Oxides, 115, 212 Oxygen Consumption, 212, 223 P Pain Threshold, 100, 212 Palliative, 212, 231 Pancreas, 163, 200, 212 Pancreatic, 144, 176, 212 Pancreatic cancer, 144, 212 Pancuronium, 51, 212 Panic, 8, 21, 25, 79, 94, 104, 148, 192, 198, 212 Panic Disorder, 8, 25, 79, 148, 192, 198, 212 Pantetheine, 108, 213 Paralysis, 163, 182, 189, 205, 213 Parenteral, 49, 114, 213 Paresthesias, 213 Parkinsonism, 169, 213 Paroxysmal, 85, 144, 167, 195, 213, 234 Parturition, 213, 218 Patch, 13, 26, 108, 213, 232 Patch-Clamp Techniques, 13, 213 Pathologic, 181, 197, 213, 234 Pathologies, 11, 213 Pathophysiology, 12, 213 Patient Compliance, 107, 213 Patient Education, 148, 154, 156, 161, 213 Pelvic, 213, 219, 232 Penicillin, 167, 213 Pentosan polysulfate, 123, 213 Pepsin, 177, 213, 214 Pepsin A, 177, 213, 214 Peptic, 172, 214 Peptic Ulcer, 172, 214 Peptide, 6, 10, 21, 27, 104, 105, 176, 201, 213, 214, 217, 220, 231 Perception, 53, 184, 214, 224 Peroral, 67, 214 Perphenazine, 59, 214 Pesticides, 113, 200, 214 Petrolatum, 187, 214 Phagocytosis, 43, 214 Pharmaceutical Preparations, 189, 214, 219 Pharmacodynamic, 60, 214 Pharmacokinetic, 32, 55, 60, 88, 214
Pharmacologic, 14, 167, 170, 191, 195, 214, 232, 234 Phenazopyridine, 124, 214 Phencyclidine, 110, 214 Phenobarbital, 35, 74, 81, 148, 214 Phenolphthalein, 187, 214 Phenotype, 20, 21, 69, 214 Phenyl, 109, 111, 115, 124, 205, 214 Phenylalanine, 213, 215, 233 Phobia, 125, 215 Phobic Disorders, 215 Phosphates, 215 Phosphodiesterase, 215, 224 Phospholipases, 215, 226 Phosphoric Acids, 113, 215 Phosphorus, 173, 215 Phosphorylation, 8, 17, 215 Physiologic, 164, 172, 184, 195, 201, 215, 222, 233 Physiology, 5, 24, 53, 68, 75, 76, 83, 164, 187, 215 Physostigmine, 89, 90, 209, 215 Picrotoxin, 75, 215 Pigment, 19, 204, 205, 215 Pilot study, 55, 215 Pineal Body, 215 Pineal gland, 13, 215 Piroxicam, 101, 215 Pituitary Gland, 181, 182, 192, 216 Placenta, 55, 216, 218 Plant Growth Regulators, 195, 216 Plants, 165, 169, 170, 171, 172, 174, 178, 193, 194, 201, 210, 216, 232 Plasma cells, 168, 216 Plasma protein, 31, 165, 216, 226 Plasmids, 11, 216 Plasticity, 8, 16, 216 Platelet Activation, 216, 226 Platelet Aggregation, 192, 216 Platinum, 203, 216 Pleomorphic, 211, 216 Podophyllotoxin, 189, 217 Point Mutation, 24, 217 Poisoning, 35, 42, 57, 169, 183, 200, 205, 208, 215, 217 Policy Making, 194, 217 Polycystic, 145, 217 Polymorphic, 184, 217 Polypeptide, 102, 166, 179, 180, 191, 213, 217, 218, 220 Polysaccharide, 168, 194, 217 Pons, 217, 223
248 Diazepam
Portal Pressure, 217, 224 Post partum, 32, 217 Posterior, 167, 170, 176, 186, 212, 215, 217 Postnatal, 82, 217 Postoperative, 72, 205, 216, 217 Postsynaptic, 8, 18, 75, 217, 226, 230 Post-translational, 23, 217 Potassium, 18, 217, 221 Potentiates, 88, 217 Potentiating, 17, 33, 166, 217 Potentiation, 16, 61, 76, 89, 103, 217, 226 Practice Guidelines, 142, 217 Precursor, 169, 185, 186, 188, 210, 215, 218, 233 Prednisolone, 87, 218 Pre-eclamptic, 61, 186, 218 Prefrontal Cortex, 12, 218 Premedication, 3, 29, 30, 38, 39, 48, 53, 55, 62, 64, 67, 84, 89, 109, 218, 225 Prenatal, 82, 187, 218 Presynaptic, 186, 218, 230 Presynaptic Terminals, 186, 218 Probe, 11, 218 Procaine, 202, 218 Prodrug, 192, 218 Progesterone, 206, 218, 228 Progression, 149, 167, 218 Progressive, 16, 26, 97, 149, 175, 177, 183, 186, 194, 208, 209, 212, 216, 218, 223, 233 Projection, 200, 210, 218, 221, 222 Prolactin, 61, 218 Proline, 112, 179, 219 Promazine, 91, 219 Promethazine, 68, 124, 219 Promoter, 7, 27, 219 Prone, 93, 219 Prophase, 219, 230 Prophylaxis, 219, 236 Propofol, 31, 47, 55, 74, 219 Propranolol, 50, 67, 86, 90, 170, 219 Propylene Glycol, 68, 219 Prospective study, 65, 219 Prostaglandins, 106, 169, 199, 206, 219 Prostaglandins A, 199, 219 Prostaglandins F, 206, 219 Prostate, 144, 219, 232 Protective Agents, 174, 219 Protein Binding, 46, 90, 220 Protein C, 165, 166, 201, 220, 233 Protein Conformation, 166, 201, 220 Protein S, 122, 145, 172, 180, 189, 193, 209, 220, 224
Proteolytic, 165, 179, 191, 220 Protocol, 45, 122, 220 Proton Pump, 39, 220 Protons, 197, 220, 222 Pruritus, 185, 197, 219, 220 Psychiatric, 8, 12, 57, 70, 71, 124, 125, 220, 226 Psychiatry, 9, 12, 15, 23, 34, 42, 43, 44, 52, 66, 71, 74, 80, 191, 220, 228, 234 Psychic, 109, 210, 220, 225 Psychogenic, 220, 234 Psychological Tests, 80, 220 Psychology, 5, 7, 19, 21, 41, 50, 87, 185, 220 Psychomotor, 38, 48, 50, 67, 71, 81, 90, 174, 183, 209, 220 Psychomotor Performance, 38, 48, 67, 90, 220 Psychophysiology, 53, 88, 90, 220 Psychosis, 168, 221 Psychotherapy, 125, 221 Psychotomimetic, 166, 184, 221 Psychotropic, 63, 80, 221 Public Policy, 141, 221 Publishing, 26, 221 Pulmonary, 172, 180, 181, 221, 229, 234, 235, 236 Pulmonary Artery, 172, 221, 235 Pulmonary Embolism, 221, 236 Pulmonary hypertension, 181, 221 Punctures, 55, 221 Pyramidal Cells, 184, 221 Pyridostigmine Bromide, 113, 221 Q Quaternary, 212, 220, 221, 225 Quinidine, 32, 177, 221 Quinine, 149, 177, 221 R Race, 109, 110, 206, 222 Radiation, 167, 171, 188, 197, 204, 206, 213, 222, 236 Radiation therapy, 197, 213, 222 Radioactive, 106, 117, 171, 195, 197, 201, 207, 211, 222 Radioactivity, 106, 222 Radioimmunoassay, 6, 10, 102, 106, 109, 117, 222 Radioisotope, 222, 232 Randomized, 11, 31, 32, 48, 49, 63, 64, 71, 72, 186, 222 Reagent, 189, 222 Receptor, 6, 7, 11, 13, 14, 16, 18, 20, 21, 23, 24, 25, 26, 27, 28, 34, 37, 45, 50, 58, 75,
Index 249
80, 82, 87, 91, 103, 104, 105, 106, 108, 116, 120, 164, 168, 172, 173, 176, 178, 185, 189, 191, 197, 206, 214, 222, 225, 226 Receptors, Serotonin, 222, 225 Recombinant, 9, 24, 58, 60, 108, 119, 222, 234 Recombinant Proteins, 108, 119, 222 Rectal, 30, 32, 33, 34, 35, 38, 39, 45, 48, 54, 61, 64, 67, 71, 72, 122, 129, 130, 222 Rectum, 169, 173, 184, 191, 192, 199, 202, 219, 222 Recurrence, 177, 222 Red Nucleus, 170, 222 Refer, 1, 61, 179, 185, 191, 192, 193, 196, 200, 203, 208, 209, 221, 223, 235 Reflex, 11, 38, 66, 81, 223 Refraction, 223, 227 Refractory, 26, 39, 64, 223 Regimen, 186, 213, 223 Relapse, 19, 107, 223 Relaxant, 192, 223 Reliability, 106, 223 Renal failure, 183, 223 Renin, 174, 223 Renin-Angiotensin System, 174, 223 Resection, 46, 223 Respiration, 100, 101, 174, 176, 182, 207, 223 Respiratory Physiology, 223, 234 Response rate, 4, 14, 223 Restoration, 13, 223 Resuscitation, 187, 223 Retinoblastoma, 144, 223 Retrobulbar, 55, 223 Retrospective, 40, 223 Retrospective study, 40, 223 Reversion, 174, 224 Rheumatism, 198, 224 Rheumatoid, 201, 216, 224 Rheumatoid arthritis, 201, 216, 224 Ribose, 164, 224 Ribosome, 224, 232 Risk factor, 219, 224 Ritanserin, 81, 224 Rod, 177, 224 Rodenticides, 214, 224 Rolipram, 40, 224 Rubber, 114, 163, 224 S Saccharin, 5, 224 Salicylate, 124, 224 Saliva, 106, 116, 224
Salivary, 190, 212, 224 Salivary glands, 190, 224 Salivation, 118, 194, 224 Saphenous, 181, 224 Saphenous Vein, 181, 224 Schizoid, 224, 236 Schizophrenia, 12, 25, 34, 43, 80, 104, 105, 224, 236 Schizotypal Personality Disorder, 184, 224, 236 Sclerosis, 144, 149, 225 Scopolamine, 9, 48, 124, 171, 225 Screening, 178, 225 Sebaceous, 225 Sebaceous gland, 225 Sebum, 19, 225 Secretion, 13, 68, 83, 108, 120, 177, 181, 196, 197, 200, 202, 207, 224, 225 Segmentation, 57, 225 Self Administration, 11, 225 Self Care, 123, 225 Semen, 219, 225 Seminiferous tubule, 225, 228 Semisynthetic, 189, 225 Sensibility, 166, 225 Sensitization, 5, 10, 225 Serologic, 198, 225 Serotonin, 20, 21, 123, 166, 169, 173, 177, 178, 192, 222, 224, 225, 226, 233 Sertraline, 46, 226 Serum, 18, 34, 35, 40, 43, 49, 66, 90, 102, 108, 109, 116, 165, 179, 222, 225, 226 Serum Albumin, 34, 102, 108, 109, 222, 226 Sex Characteristics, 164, 226, 230 Sex Determination, 145, 226 Signal Transduction, 13, 226 Signs and Symptoms, 148, 223, 226 Skeletal, 40, 67, 100, 177, 182, 208, 221, 226, 227 Skeleton, 201, 226 Skull, 173, 182, 226, 230 Sleep Deprivation, 33, 226 Small intestine, 186, 193, 196, 200, 226 Smooth muscle, 118, 165, 170, 173, 174, 192, 196, 207, 210, 219, 223, 226, 227, 229 Social Behavior, 13, 88, 226 Sodium, 19, 75, 76, 83, 101, 109, 110, 123, 149, 184, 221, 222, 226, 227, 229, 231, 234 Sodium Channels, 222, 227, 231, 234 Sodium Fluoride, 149, 227 Soft tissue, 173, 226, 227 Solvent, 67, 171, 189, 194, 212, 219, 227
250 Diazepam
Soma, 221, 227 Soman, 113, 122, 227 Somatic, 68, 164, 197, 202, 204, 206, 218, 227 Somatic cells, 204, 206, 227 Sonogram, 227, 232 Sound wave, 180, 227, 232 Spasm, 40, 169, 181, 196, 205, 227 Spasticity, 70, 171, 227 Spatial disorientation, 185, 227 Specialist, 150, 227 Specificity, 9, 164, 227 Spectrometer, 38, 227 Spectrum, 12, 227 Sperm, 40, 177, 225, 227 Spermatozoa, 112, 225, 228 Spina bifida, 59, 228 Spinal cord, 43, 170, 171, 175, 176, 205, 209, 223, 228 Sporadic, 223, 228 Stapes, 197, 228 Status Epilepticus, 16, 29, 37, 39, 56, 59, 64, 71, 228 Steady state, 17, 228 Steel, 177, 228 Steroid, 182, 212, 228 Stimulant, 19, 48, 166, 184, 196, 205, 215, 228 Stimulus, 4, 11, 14, 74, 118, 189, 190, 200, 213, 215, 223, 228, 231 Stomach, 117, 160, 163, 184, 189, 192, 196, 200, 202, 208, 213, 226, 228 Strabismus, 72, 228 Stress, 8, 18, 25, 86, 91, 105, 125, 175, 182, 192, 208, 224, 228, 234 Striatum, 12, 116, 211, 228 Stroke, 43, 140, 228 Stupor, 160, 208, 228 Styrene, 224, 228 Subacute, 199, 228 Subarachnoid, 195, 228 Subclinical, 199, 225, 229 Subcutaneous, 186, 211, 213, 229 Subiculum, 196, 229 Subspecies, 227, 229 Substance P, 189, 205, 225, 229 Substrate, 22, 66, 188, 229 Suction, 213, 229 Superoxide, 11, 229 Superoxide Dismutase, 11, 229 Supplementation, 86, 165, 229 Suppression, 6, 181, 229
Suprachiasmatic Nucleus, 13, 229 Supraspinal, 171, 229 Surfactant, 189, 229 Suspensions, 112, 229 Sweat, 19, 198, 229 Sweat Glands, 229 Sympathomimetic, 166, 184, 185, 188, 205, 210, 229 Symphysis, 219, 229 Symptomatic, 167, 176, 191, 229 Symptomatic treatment, 167, 176, 229 Synapsis, 229, 230 Synaptic, 8, 16, 210, 226, 230 Synaptic Transmission, 210, 230 Syncope, 71, 230 Synergistic, 76, 103, 218, 230 Systemic, 18, 68, 86, 134, 169, 172, 183, 185, 188, 199, 200, 211, 218, 222, 230, 233, 236 Systolic, 197, 230 T Tardive, 169, 177, 230 Telangiectasia, 145, 230 Telencephalon, 171, 230 Temporal, 24, 62, 166, 190, 195, 196, 230 Temporal Lobe, 24, 166, 230 Teratogenic, 185, 230 Teratogenicity, 11, 122, 230 Testosterone, 58, 230 Thalamic, 170, 230 Thalamic Diseases, 170, 230 Thalamus, 184, 202, 218, 230 Theophylline, 185, 230 Therapeutics, 23, 39, 46, 54, 66, 134, 231 Thermal, 53, 185, 231 Third Ventricle, 198, 215, 230, 231 Threshold, 8, 117, 190, 197, 231 Thrombosis, 220, 228, 231 Thyroid, 197, 231, 233 Thyroid Gland, 197, 231 Thyroid Hormones, 231, 233 Thyrotropin, 61, 231 Thyroxine, 165, 215, 231 Tiapride, 33, 231 Tinnitus, 85, 148, 149, 231, 235 Tocainide, 149, 231 Tolerance, 5, 7, 9, 18, 23, 34, 75, 93, 97, 178, 231 Tonic, 41, 82, 178, 205, 231 Topical, 100, 189, 197, 214, 231 Toxic, iv, 170, 171, 177, 182, 183, 188, 198, 209, 210, 217, 228, 232 Toxicity, 11, 63, 84, 186, 214, 215, 232
Index 251
Toxicologic, 115, 232 Toxicology, 38, 39, 42, 54, 75, 76, 102, 124, 142, 232 Toxins, 106, 168, 199, 207, 232 Trace element, 191, 232 Tracer, 102, 109, 232 Traction, 177, 232 Tranquillizer, 48, 232 Transdermal, 100, 232 Transduction, 226, 232 Transfection, 7, 172, 232 Transferases, 194, 232 Translation, 8, 189, 209, 232 Translational, 23, 69, 232 Translocation, 189, 232 Transmitter, 23, 163, 185, 190, 204, 210, 232 Transurethral, 41, 232 Transurethral resection of the prostate, 41, 232 Transvaginal ultrasound, 31, 232 Trauma, 82, 183, 209, 232 Trees, 177, 224, 232 Tremor, 205, 213, 233 Triazolam, 14, 39, 67, 233 Trichomoniasis, 206, 233 Tricuspid Atresia, 181, 233 Tricyclic, 166, 177, 186, 198, 233 Trigger zone, 169, 233 Trisomy, 167, 233 Tryptophan, 11, 179, 225, 233 Tryptophan Hydroxylase, 11, 233 Tubal ligation, 32, 233 Tubercle, 211, 233 Tuberculosis, 180, 201, 233 Tuberculostatic, 201, 233 Tuberous Sclerosis, 145, 233 Tumour, 42, 233 Tyrosine, 11, 185, 233 U Unconscious, 110, 161, 167, 198, 233 Urea, 19, 229, 233 Urethra, 219, 232, 233, 234 Urinary, 62, 72, 124, 182, 199, 214, 225, 233, 234 Urinary Retention, 62, 234 Urinary tract, 214, 234 Urinate, 234 Urine, 18, 63, 81, 106, 116, 165, 168, 172, 180, 195, 199, 233, 234 Urticaria, 176, 197, 234
Uterus, 183, 188, 190, 212, 218, 232, 233, 234 V Vaccine, 164, 220, 234 Vagina, 232, 234 Valproic Acid, 35, 234 Vascular, 101, 165, 172, 174, 195, 199, 203, 206, 211, 216, 231, 234 Vascular Headaches, 172, 234 Vasculitis, 66, 234 Vasodilation, 185, 234 Vasodilator, 172, 173, 185, 196, 210, 234 VE, 43, 234 Vector, 11, 232, 234 Vein, 200, 211, 217, 224, 234 Venlafaxine, 60, 234 Venous, 29, 72, 210, 211, 217, 220, 233, 234, 236 Venous Thrombosis, 234, 236 Ventilation, 14, 189, 234 Ventral, 12, 198, 211, 217, 234 Ventricle, 166, 170, 175, 181, 196, 211, 221, 230, 231, 233, 235 Ventricular, 92, 181, 191, 233, 235 Venules, 173, 174, 206, 235 Verapamil, 112, 235 Vertebrae, 228, 235 Vertebral, 172, 228, 235 Vertigo, 12, 94, 124, 185, 204, 235 Vesicular, 196, 206, 235 Vestibular, 11, 97, 124, 235 Vestibule, 235 Vestibulocochlear Nerve, 197, 231, 235 Vestibulocochlear Nerve Diseases, 197, 231, 235 Veterinary Medicine, 74, 75, 141, 235, 236 Viral, 6, 232, 235 Virulence, 232, 235 Virus, 6, 11, 27, 44, 175, 193, 232, 235 Viscera, 227, 235 Vitro, 235 Vivo, 55, 235 W Wakefulness, 183, 236 Warfarin, 35, 72, 236 White blood cell, 163, 168, 199, 202, 203, 210, 216, 236 X Xenograft, 167, 236 X-ray, 211, 222, 236 Xylazine, 74, 75, 236
252 Diazepam
Y
Yeasts, 192, 214, 236
Index 253
254 Diazepam
Index 255
256 Diazepam
