NARCOLEPSY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Narcolepsy: 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: 0-597-84125-X 1. Narcolepsy-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 narcolepsy. 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 NARCOLEPSY ............................................................................................ 3 Overview........................................................................................................................................ 3 Federally Funded Research on Narcolepsy..................................................................................... 3 E-Journals: PubMed Central ....................................................................................................... 36 The National Library of Medicine: PubMed ................................................................................ 36 CHAPTER 2. NUTRITION AND NARCOLEPSY .................................................................................. 79 Overview...................................................................................................................................... 79 Finding Nutrition Studies on Narcolepsy ................................................................................... 79 Federal Resources on Nutrition ................................................................................................... 82 Additional Web Resources ........................................................................................................... 83 CHAPTER 3. ALTERNATIVE MEDICINE AND NARCOLEPSY ............................................................ 85 Overview...................................................................................................................................... 85 National Center for Complementary and Alternative Medicine.................................................. 85 Additional Web Resources ........................................................................................................... 89 General References ....................................................................................................................... 90 CHAPTER 4. DISSERTATIONS ON NARCOLEPSY .............................................................................. 91 Overview...................................................................................................................................... 91 Dissertations on Narcolepsy ........................................................................................................ 91 Keeping Current .......................................................................................................................... 92 CHAPTER 5. CLINICAL TRIALS AND NARCOLEPSY ......................................................................... 93 Overview...................................................................................................................................... 93 Recent Trials on Narcolepsy ........................................................................................................ 93 Keeping Current on Clinical Trials ............................................................................................. 94 CHAPTER 6. PATENTS ON NARCOLEPSY ......................................................................................... 97 Overview...................................................................................................................................... 97 Patents on Narcolepsy.................................................................................................................. 97 Patent Applications on Narcolepsy............................................................................................ 103 Keeping Current ........................................................................................................................ 113 CHAPTER 7. BOOKS ON NARCOLEPSY........................................................................................... 115 Overview.................................................................................................................................... 115 Book Summaries: Online Booksellers......................................................................................... 115 The National Library of Medicine Book Index ........................................................................... 116 Chapters on Narcolepsy ............................................................................................................. 117 CHAPTER 8. MULTIMEDIA ON NARCOLEPSY ................................................................................ 119 Overview.................................................................................................................................... 119 Bibliography: Multimedia on Narcolepsy .................................................................................. 119 CHAPTER 9. PERIODICALS AND NEWS ON NARCOLEPSY ............................................................. 121 Overview.................................................................................................................................... 121 News Services and Press Releases.............................................................................................. 121 Newsletter Articles .................................................................................................................... 125 Academic Periodicals covering Narcolepsy................................................................................ 125 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 127 Overview.................................................................................................................................... 127 U.S. Pharmacopeia..................................................................................................................... 127 Commercial Databases ............................................................................................................... 128 Researching Orphan Drugs ....................................................................................................... 129 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135
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Other Commercial Databases..................................................................................................... 137 The Genome Project and Narcolepsy ......................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 143 Overview.................................................................................................................................... 143 Patient Guideline Sources.......................................................................................................... 143 Associations and Narcolepsy...................................................................................................... 149 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 NARCOLEPSY DICTIONARY.................................................................................................... 163 INDEX .............................................................................................................................................. 221
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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 narcolepsy 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 narcolepsy, 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 narcolepsy, 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 narcolepsy. 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 narcolepsy, 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 narcolepsy. 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 NARCOLEPSY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on narcolepsy.
Federally Funded Research on Narcolepsy The U.S. Government supports a variety of research studies relating to narcolepsy. 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 narcolepsy. 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 narcolepsy. The following is typical of the type of information found when searching the CRISP database for narcolepsy: •
Project Title: A SCREENING LIBRARY FOR PEPTIDE-ACTIVATED GPCR'S Principal Investigator & Institution: Saunders, John; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 30-SEP-2003 Summary: One subset of the G-protein coupled receptor (GPCR) superfamily is that which is activated by a peptide carrying an obligatory positively charged residue
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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(GPCR-PA+). This subclass is exemplified by receptors for melanocortins, GnRH galanin, MCH, orexin and chemokine receptors variously involved in eating disorders, reproductive disorders, pain, narcolepsy, obesity, and inflammation. In Phase-I, a region of chemical property space enriched in GPCR ligands was identified. This was used to design and synthesize a 'test' library of 2025 single, pure compounds to sample portions of this property space associated with GPCR-PA+ ligands. This library was evaluated by high-throughput screening against three different receptors and found to be highly enriched in ligands (4.5 to 61-fold) compared to a control set of 2024 randomly selected compounds. In Phase II we propose to expand the size of this library to at least 6749 compounds to complete the sampling of this GPCR-PA+ ligand-rich region and to better define it's borders. This completed library will be screened against an expanded array of receptor targets and hits so identified used as a starting point for lead optimization against a selected target. The resulting library should be a valuable resource for the rapid identification of ligands to a range of therapeutically important receptors. PROPOSED COMMERCIAL APPLICATIONS: The project, if successful, will result in a library of small molecule compounds with a high probability of yielding multiple modesty, active molecules for any G-protein coupled receptor for positively charged peptide ligands. From this information, an interactive process of design, synthesis and screening will afford potent, selective ligands, Thus, this library will accelerate Neurocrine's in-house drug discovery efforts focused on members of this class of receptors and against novel members as they become available. Additionally, the library may be licensed to other companies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVORIAL HYDROXYBUTYRATE
PHARMACOLOGY
OF
GAMMA
Principal Investigator & Institution: Roll, John M.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) Gamma-hydoxybutyrate (GHB) is a compound with a mixed reputation. On one hand it has been used quite successfully to treat persons suffering from narcolepsy and appears to be promising in the treatment of alcohol and opiate withdrawal. Furthermore it has been investigated as a treatment for schizophrenia, cocaine abuse, Parkinson's disease and night eating syndrome. On the other hand, GHB has been abused, presumably for its' psychoactive effects, with disastrous consequences including the development of a severe withdrawal syndrome, coma and even death. GHB has also been used to facilitate the commission of sexual assaults by surreptitiously providing it to the victim. Several investigators have suggested that GHB is a reinforcer with abuse potential while others have suggested exactly the opposite. Despite this wide-ranging history, the behavioral pharmacology of GHB has not been thoroughly examined. We are proposing a rigorous, inpatient double blind, placebo controlled, experimental procedure for assessing the physiological consequences, subjective properties, relative reinforcing potential, direct effects and pharmacokinetics of GHB in a group of regular GHB users. Furthermore, we are proposing to assess the degree to which GHB will be self-administered by volunteers. We believe that the successful completion of the proposed study will provide us with much needed data about the human behavioral pharmacological profile of GHB in the GHB user. We believe the data collected in the proposed study will be useful in developing effective treatments for those who have overdosed on GHB, for those who are in withdrawal from GHB, and for those who are attempting to quit using GHB.
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Furthermore, it is our belief that securing a fuller understanding of this interesting compound may help explain why it has come to be abused by certain individuals. This last point may be of particular importance as it is likely that other drugs, with profiles similar to that of GHB, will enter the "Club Drug" milieu in the future and we may be able to inform policy surrounding these future agents based on a fuller understanding of GHB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN MECHANISMS IN SLEEP AND NARCOLEPSY Principal Investigator & Institution: Shiromani, Priyattam J.; Associate Professor; Neurology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-1991; Project End 30-JUN-2008 Summary: (provided by applicant): Narcolepsy has now been linked to a lesion of neurons containing the neuropeptide hypocretin (HCRT), also named orexin. However, the loss of these neurons can only be determined upon autopsy. Cerebrospinal fluid (CSF) measurements of HCRT represent a potential marker of an underlying pathology, i.e., lesion of HCRT neurons. However, for this marker to be clinically significant it is vital that we determine the relationship between number of HCRT neurons and CSF HCRT levels. Narcoleptic patients have reduced CSF levels of HCRT, a finding consistent with the loss of HCRT neurons. However, new data from Mignot's group are beginning to show that in about 10 percent of narcoleptics the CSF levels of HCRT are normal. This raises important questions about loss of HCRT neurons, and the utility of CSF levels of HCRT as an assay to diagnose narcolepsy. For instance, if a human narcoleptic has normal CSF HCRT levels does it mean that HCRT neurons are intact? Or does it suggest that the disease has not progressed to a point where a certain threshold number of HCRT neurons have not been destroyed? Because such questions cannot be easily addressed using current murine knockout, rat knockout or canine models of narcolepsy, we will utilize the hypocretin-saporin (HCRT2-SAP) neurotoxin method to lesion hypocretin and adjacent lateral hypothalamic neurons and monitor sleep and CSF HCRT-1 levels in rats. We have designed a set of aims to provide critical data to the clinician, but also provide a framework for integrating the hypocretin neurons within an overall model of sleep regulation. Specific aim 1 will test the hypothesis that a significant decrease in CSF HCRT levels is evident only after a threshold number of HCRT neurons are lost. Specific aim 2 will determine the association between CSF HCRT levels and sleep. Specifically, we will investigate whether narcoleptic-like behavior, characterized by sleep onset REM sleep periods (SOREMPs), increased REM sleep at night, and hypersomnia is evident ahead of a decline in CSF HCRT levels. Specific aim 3 will test the hypothesis that loss of a specific population of HCRT neurons is responsible for the symptoms of narcolepsy. Specific aim 4 will determine the afferents and efferents of this population of HCRT neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAINSTEM MECHANISMS OF ALERTING Principal Investigator & Institution: Morrison, Adrian R.; Professor; Animal Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1987; Project End 31-JUL-2003 Summary: (Adapted from applicant's abstract): This project seeks further understanding of the mechanisms underlying the generation and maintenance of one phase of sleep,
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REM sleep. REM normally follows the other stages of sleep, collectively known as nonREM (NREM). Its differentiating features are a total paralysis of skeletal muscles with superimposed phasic muscle twitches, electroencephalographic activity resembling wakefulness rather than NREM, and profound depression of the brain mechanisms regulating homeostasis, i.e., those controlling such vital features of life as temperature, cardiovascular activity and respiration. Further, as we demonstrated 20 years ago, the brain in REM functions much like the brain during orienting in wakefulness. The project's focus will be study of the activity of nerve cells in the amygdala of the forebrain of rats and their interactions with those in the pons of the hindbrain that have long been studied and heavily implicated in the control of REM. The investigator is stimulated by the facts that the amygdala and pons are tightly interconnected and that the amygdala is a key structure investing environmental stimuli with emotional significance. Thus, a change in sensitivity of structures like the amygdala to arousing stimuli must precede entrance into REM. Indeed, in narcoleptics the shift to REM is so poorly modulated that sufferers enter REM directly from wakefulness when confronted by such stimuli. The investigator shall record single-neuronal activity in three amygdalar nuclei, the central (CNA), basolateral (BLA) and lateral (LA), across sleep-wake states. The investigator shall determine how stimulation and suppression of key pontine neurons of different transmitter types, serotonergic, noradrenergic and cholinergic, affect spontaneously active amygdalar neurons and those responding to novel or significant auditory stimuli. These experiments address basic mechanisms likely to be altered in narcolepsy and PTSD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR AND NEUROCHEMICAL MECHANISMS OF REM SLEEP Principal Investigator & Institution: Datta, Subimal; Professor; Psychiatry; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract) The long term objective of this application is to elucidate the cellular and neurochemical mechanisms of REM sleep. More, specifically, the goal is to contribute to the existing, yet incomplete, body of knowledge on the regulation of the PPT cholinergic cell activity in relation to the generation and maintenance of REM sleep. A clearer understanding of PPT cell regulation mechanisms will move the field of sleep research closer to the development of effective treatments for human REM disorders, such as narcolepsy, cataplexy, excessive daytime sleepiness, and those REM disorders associated with psychiatric and neurological conditions such as depression and Alzheimer's disease. The central hypothesis of this proposal is that PPT cholinergic cells are stimulated via specific glutamate receptors to induce REM sleep. To test this hypothesis systematically, there are four specific aims: 1. Determine the optimal dosage of L-Glutamate in the PPT to induce the maximum amount of REM sleep. The optimal dosage will be determined by making discrete microinjections of one of five different doses of L-Glutamate or control vehicle directly into the PPT cholinergic compartment while quantifying the effects of REM sleep. 2. Identify the glutamate receptor subtype(s) that is involved in exogenous L-glutamate-microinjection-induced REM sleep. This goal will be achieved by microinjecting specific glutamate receptor antagonists directly into the PPT cholinergic cell compartment to block the REM sleep inducing effect of the optimal dose of exogenous L-glutamate. 3. Identify which glutamate receptor type, if any, is involved in the maintenance of REM sleep by endogenous glutamate. This goal will be achieved by making discrete microinjections of specific antagonists or control vehicle alone into the PPT cell compartment while
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quantifying changes in REM sleep. 4. Test the hypothesis that activation of REM-on and Wake- REM-on cells of the PPT cell compartment by specific glutamate receptors is causal for the generation of REM sleep. This aim will be achieved by applying the REM sleep suppressing glutamate receptor antagonist to identified REM-on and Wake-REMon PPT cells while recording single cell unitary activity in freely moving rats. The pharmacological identification of glutamate receptors involved with PPT-modulated REM sleep regulation will be an important step toward future experiments to elucidate the molecular mechanisms of REM sleep generation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTER FOR NARCOLEPSY AND RELATED DISORDER Principal Investigator & Institution: Mignot, Emmanuel J.; Director; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 31-MAY-2005 Summary: Narcolepsy is a disabling neurological disorder affecting more than 1 in 2,00 Americans. This program project is the only existing NIH funded multi-disciplinary program focusing on this disorder. Our previous funding has led to significant advances such as the identification and genetic characterization of canine narcolepsy [the only known animal model for this condition], the dissection of the mode of action of currently prescribed narcolepsy treatments and the discovery that HLA- DBQ1*0602, rather than the previously identified HLA-DR2 antigen, is a genuine human narcolepsy susceptibility gene. A neuroanatomical map of the structures and neurotransmitters involved in the pathophysiology of narcolepsy is also being established. A solid linkage marker for the canine narcolepsy gene, canarc-1 was also identified and the genomic segment containing the deficient gene was flanked and physically cloned using a Bacterial Artificial Chromosome (BAC) genomic library build specifically for this purpose. In the next funding period, a new project, Project B, will be initiated in Wisconsin Sleep Cohort. The goal of this project is to define the spectrum of narcolepsy and its symptoms in the general population using HLA typing in the context of an epidemiological approach. Once completed, this project will have direct clinical applications. It will provide the scientific community with the first prevalence estimate for narcolepsy without cataplexy. It will help clinicians and researchers to better define and thus treat this disorder at a time when new stimulant treatments are being increasingly used (and perhaps misused) for the treatment of narcolepsy. The second and third projects are direct continuations of our previous efforts. Project D will further characterize the neuroanatomical and neurophysiological approach. Project C will complete the cloning of canarc-1 and study the function of this deficient gene. Based on the rapid pace of our previous progress, we are confident that we will identify canarc-1 during the next funding period. Whether or not this gene is involved in human narcolepsy, the identification of canarc-1 will be a landmark in our understanding of narcolepsy and sleep control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CENTRAL MODULATION OF LOCOMOTOR RHYTHMS Principal Investigator & Institution: Garcia-Rill, Edgar E.; Professor and Director; Anatomy; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-MAR-1984; Project End 30-NOV-2001
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Narcolepsy
Summary: (Adapted from applicant's abstract): Cholinergic mesopontine cell groups, in concert with catecholaminergic (and serotonergic) neurons, participate in the descending control of locomotion and of postural muscle tone (e.g., startle response and atonia of REM sleep). As part of the Reticular Activating System (RAS), ascending projections of these cells modulate changes in state (e.g., sleep-wake cycles) and the response to afferent input (e.g., sensory gating). That is, they are in a crucial position to modulate fight vs flight responses. The applicants' work has implicated these neurons in psychiatric (e.g., schizophrenia, anxiety disorder), neurological (e.g., Parkinson's Disease) and sleep (e.g., narcolepsy, REM behavior disorder) disturbances, all of which have sleep-wake cycle and motor dysregulation in common. Studies during the previous grant period identified the presence of a novel mechanism whereby mesopontine cholinergic neurons may induce changes in state in descending target neurons. The proposed studies will investigate the characteristics and pharmacological control of this mechanism with a view towards determining the manner in which postural and locomotion systems are switched on and off. In addition, the applicants have developed a preparation in the behaving animal allowing the non-invasive recording of a waveform which is a measure of the ascending output of the RAS. Preliminary data suggest that localized injections of neuroactive agents into the mesopontine region can modulate this vertex-recorded waveform. The proposed studies will investigate the characteristics and pharmacological control of this waveform with a view towards determining the manner in which arousal and sensory gating systems are controlled. This work is of critical importance in the understanding of, and design of therapeutic strategies for, a number of psychiatric, neurological and sleep-wake cycle disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CIRCADIAN AND AMINERGIC REGULATION OF OREXIN NEURONS Principal Investigator & Institution: Scammell, Thomas E.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The neuropeptide orexin (also known as hypocretin) plays a central role in the regulation of sleep/wake behavior and the pathology of narcolepsy. People with narcolepsy have difficulty maintaining wakefulness and often have intrusions of REM sleep-like phenomena into wakefulness. These individuals often have decreased numbers of orexin neurons and undetectable concentrations of orexin in cerebrospinal fluid, and mice and dogs with mutations in the genes for orexin or its receptors have a phenotype resembling narcolepsy. As orexin appears necessary for the normal maintenance of wakefulness and suppression of REM sleep, it is critical that we identify the factors that influence the activity of orexin neurons. We propose a model in which orexin neurons promote wakefulness and inhibit REM sleep by activating aminergic arousal regions, and, in turn, the orexin neurons are activated by these aminergic regions. Thus, orexin neurons should be active during wakefulness, and this orexin neuron activity should further increase the activity of aminergic arousal regions, thereby promoting and stabilizing wakefulness. By increasing aminergic activity, orexin neurons also should inhibit REM sleep. In the absence of this positive feedback, the amount of wakefulness should be reduced, bouts of wakefulness should be shorter, and the amount of REM sleep should be increased. Wakefulness and REM sleep are tightly regulated by circadian factors, and we also propose that orexin neurons are influenced by circadian factors, thus contributing to the circadian regulation of sleep/wake
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9
behavior. In rats, this circadian signal would facilitate the activation of orexin neurons during the night phase, thereby promoting wakefulness and suppressing REM. In the absence of orexin, the circadian influence on wakefulness and REM should be lost. Our proposed experiments will test the roles of these aminergic and circadian influences. We will first determine whether orexin neurons are active during wakefulness and whether this activation is dependent upon circadian phase. We will use the expression of Fos protein and c-fos mRNA in orexin neurons as well as the concentration of orexin in CSF as indicators of orexin neuron activity, and we will correlate these measures with sleep/wake behavior. We then will determine whether orexin mediates circadian influences on sleep/wake architecture by studying rodents in a light/dark cycle or in constant darkness; these experiments will use two models of orexin deficiency: orexin knockout mice and transgenic rats with an acquired loss of orexin neurons similar to human narcolepsy. Next, we will determine whether orexin neurons are innervated by aminergic arousal regions and express excitatory amine receptors. To test the importance of these aminergic afferents, we will study the response to amphetamine of orexin knockout mice and transgenic rats lacking orexin neurons. By investigating these circadian and aminergic influences on orexin neurons, we will gain critical insights into the normal function of orexin neurons that should provide new perspectives on normal behavioral state control and the neurobiology of narcolepsy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONFERENCE ON MOLECULAR CLOCKS Principal Investigator & Institution: Young, Michael W.; Professor & Howard Hughes Investigator; Keystone Symposia Drawer 1630, 221 Summit Pl #272 Silverthorne, Co 80498 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2001 Summary: (Applicant's Abstract): Impressed by the results of a particularly successful and oversubscribed international meeting on Molecular Clocks held at the Juan March Foundation in May of 1998, a Keystone meeting on the subject is proposed for 2001. The sub-areas to be represented include (1) Molecular and genetics studies of circadian behavioral rhythms in animal systems, with emphasis on newly identified genes, the strong homologies among clock genes in the animal kingdom, and their mechanisms of action. (2) The molecular pathways that afford resetting of clocks and the sleep/wake cycle in response to light. Our understanding of the molecular mechanisms associated with phototransduction and clock gene responses has grown significantly in just the past year. The role of cryptochromes, which act as circadian photoreceptors in some systems, is now widely studied. (3) Regulation of wake/sleep behavior. Biochemical strategies for conveying signals from molecular clocks to timed behavior have been clarified in the past year. (4) Genetic control of human wake/sleep cycles. The first hereditary variations in human circadian rhythms were reported last year as well as a partial molecular description of narcolepsy in mammalian models. (5) Plant, fungal, and bacterial clocks, and modeling molecular oscillators. Non-animal model systems continue to provide some of our greatest insights into biochemical mechanisms underlying circadian [clocks]. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--CLINICAL/LABORATORY DATA BASE AND TISSUE BANK Principal Investigator & Institution: Dement, William C.; Stanford University Stanford, Ca 94305
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Timing: Fiscal Year 2001 Summary: The Stanford Narcoleptic Canine Colony is an indispensable research resource for this program project, other NIH grants and other investigators. In this Core, we are requesting funds to maintain the colony and research canines required for this program project and collaborating investigators. The canine database contains information on almost 500 animals. This includes disease status, severity of the symptoms of narcolepsy if applicable, genetic and pedigree information, tissue collection (nature and location, if any) and other information relevant to the health of the animal. A pharmaceutical compound database recording the observed effects of more than 200 compounds on the symptoms of narcolepsy is also maintained. The Core is also the primary source of information and tissue for human narcolepsy subjects and relatives. Clinical files containing medical history, pedigree information, questionnaire data and HLA typing results are the primary source of the data. The human narcolepsy database contains genetic and clinical information on more than 1,800 subjects. It is the responsibility of the Principal Investigator to assure that the Center for Narcolepsy scientists work as an integrated team and that through this scientific leadership, pursuit of overall goals of the program is consistent. A weekly research meeting is held to facilitate communication among the investigators and between the research staff and administrative staff. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPENDENCE POTENTIAL OF GHB, GBL AND 1,4-BD Principal Investigator & Institution: Weerts, Elise M.; Assistant Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Gamma-hydroxybutyrate (GHB) is currently under investigation as a potential treatment for narcolepsy and alcohol dependence. Although GHB is currently classified as a Schedule I substance under the controlled substances act, illicit use of GHB, and its precursors gamma-butyrolactone (GBL) and 1,4butanediol (1,4-BD), is on the rise. The ability of GHB and its precursors to produce physical dependence has not been evaluated in controlled studies in humans or laboratory animals. The goal of the proposed research is to evaluate the physical dependence potential of GHB, GBL and 1,4-BD. Two specific aims are proposed: Aim 1 is to characterize the behavioral effects of GHB, GBL, 1,4-BD after acute and chronic intragastric drug administration in baboons. Aim 2 is to characterize physical dependence and the withdrawal syndrome for GHB and its precursors GBL and 1,4-BD in baboons. First, GHB, GBL and 1,4-BD will be administered alone and then in combination with the GHB antagonist NCS-382. Changes in food-maintained behavior, observed behaviors, and fine motor coordination, when compared to controls, will be evaluated. Next a high dose of GHB, GBL or 1,4-BD will be administered chronically via continuous i.g. infusion and changes in food-maintained behavior, observed behaviors, and fine motor coordination, when compared to vehicle control, will be evaluated. Then, the GHB antagonist NCS-382 will be administered to baboons that have been chronically treated with GHB, GBL or 1,4-BD. Evidence for a precipitated withdrawal syndrome will be determined based on changes in food-maintained behavior, observed behaviors, and fine motor coordination when compared those same behaviors recorded during the vehicle baseline and following administration of the antagonist alone. Finally, chronic treatment with GHB, GBL or 1,4-BD will be abruptly discontinued. The presence and time-course of a spontaneous withdrawal syndrome will be determined based on comparison with the same behavioral measures determined during a) the vehicle
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baseline condition and b) during the chronic drug dosing condition. The results of these studies will provide critical information on the behavioral pharmacology and physical dependence potential of GHB and its precursors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF NARCOLEPSY Principal Investigator & Institution: Longstreth, W T.; Associate Professor; Neurology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy, an episodic loss of muscle tone triggered by intense emotions. The disease usually manifests by adolescence. Almost all patients with narcolepsy carry the DQB1 0602 gene, an HLA marker for the haplotype associated with narcolepsy. Like other investigators, we hypothesize that although genetic factors may predispose people to develop narcolepsy, environmental exposures between conception and adolescence are essential for expression of the disease. We propose to test this hypothesis and examine other epidemiologic features of narcolepsy with four interrelated epidemiologic studies. First of all, we will estimate the prevalence of narcolepsy using several overlapping methods of case ascertainment and create a registry of all patients who have narcolepsy, as of 2001 July 1, among the close to 1.7 million residents of King County, Washington. Secondly, we will characterize the clinical features and functional consequences of narcolepsy in all patients in the narcolepsy registry. Thirdly, we will survey sleep complaints among a sample of King County residents identified through random-digit dialing. We will determine whether or not these subjects carry a marker for narcolepsy susceptibility, namely the DQB1 0602 gene. If any patients with narcolepsy are identified, they will be added to the narcolepsy registry. For subjects without narcolepsy, the study will yield estimates for the prevalence of sleep complaints among those who do and do not carry the DQB1 0602 gene in this sample of the general population. Finally, and most importantly, we will evaluate potential risk factors for narcolepsy by means of a population-based case-control study. Cases will come from patients in the narcolepsy registry, and control subjects will be the subset of those identified through random-digit dialing who carry the DQB1 0602 gene. We will assess environmental risk factors in genetically susceptible individuals by requiring all subjects, both cases and controls, to carry the DQB1 0602 gene. Exposures occurring before late adolescence, especially to chemicals that can affect brain function, will be studied. Although narcolepsy is not known to shorten one's life, it is a lifelong disorder that can cause severe disability. The long- term goals of these four interrelated epidemiologic studies are to learn more about the etiology of narcolepsy and to reduce its occurrence by identifying potentially modifiable, risk factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EYE-COM 6/MSV CAMERA: A DROWSINESS DETECTING BIOSENSOR Principal Investigator & Institution: Torch, William C.; Ndc & Wsdc Washoe Sleep Disorders Center Disorders Center Reno, Nv 89502 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAY-2002 Summary: (provided by applicant) This SBIR study proposes the creation of the realtime operator fatigue-monitoring EYE-COM 6 CAMERA System (EC-6 Cam)--a composite biosensor derived from the fuision of two complimentary monitoring
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technologies: (i) the MULTI-SENSORY VISION IR CAMERA (MS V-Cam) and (ii) the EYE-COM 5 poly-sensor scanning array. Using computer imaging technology, MS VCam analyzes video images of an operator's face to extract ocular and eye-blink characteristics, pupillary size and movement, and eye--metrics that typically reflect wakefulness/drowsiness. EYE-COM 5 monitors eyelid movement via a close range IR poly-sensor based on differential IR-light reflection off the eyes and lids. The multisensory EC-6 Cam, based on the fusion of these two technologies, overcomes limitations of the each technology. Through its linear array of IR biosensors and a proximallyplaced IR micro-camera attached to a wrap-around eyeglass frame, EC 6 measures eyeblink and ocular-related parameters both sedentary and highly mobile individuals in all lighting situations and unlimited domains. Its metrics include eye-blink velocity (EBV), acceleration (EBA), -frequency (EBF), -duration (EBD), percentage-time eyes are closed (PERCLOS), pupillary size, eye movements and gaze. The goal of this project is to build, test and validate, by means of performance/vigilance protocols, the highly versatile and robust composite EC-6 Cam which will work in all stationary and mobile domains. EC6Cam makes possible the derivation of a Composite Fatigue Index (CFI) based on multiple, rather than a single fatigue-related metric alone (e.g. PERCLOS). EC-6 Cam, as a Communicator and Controller, has at least 30 other commercial civilian and military applications. PROPOSED COMMERCIAL APPLICATIONS: Safety, communication, assistive and research applications include monitoring operator-alertness/drowsiness in trucks, buses, trains, avionics/aerospace- marine/submarine-light/heavy industry and military operations, including pilot G-LOC/fatigue; for silent communications; as an electro-mechanical, electronic or computer remote communicator/controller for the elderly, injured, disabled or respirator-dependent ICU patient, as an ambulatory clinical/research biosensor for neurological disorders, sleep/EEG- medicalpsychological- and pharmaceutical studies measuring therapeutic/toxic effects (e.g. modafanil/stimulants in narcolepsy; L-DOPA in Parkinson's disease; alcohol or amphetamine driver impairment); as a lie-detector and as a robotic controller. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION IN RAT BRAIN Principal Investigator & Institution: Sutcliffe, J Gregor.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 30-NOV-2005 Summary: (provided by applicant): We propose to continue our studies on brain mRNAs so as to better our understanding of patterns of brain gene expression, to identify and solve the structures of novel brain proteins with spatially restricted expression within the brain, and to gain insights into their functional nature and their contribution to the behavioral and physiological operation of the organism. We will use the newly developed and automated TOGA technology to identify cDNA clones of mRNAs highly enriched in their expression in the hypothalamus, so as to identify those whose expression is restricted to discrete hypothalamic nuclei, or the striatum, so as to compile a complete dossier on the molecular nature of medium spiny neurons. Fulllength clones of novel ensemble members will be isolated and their sequences determined so as to team the identity of their encoded proteins. The sites of expression will be determined by in situ hybridization and unmunohistochemical methods using antisera to synthetic peptides corresponding to domains of the deduced protein sequences. We will use the acquired information to form hypotheses about function and test these by biochemical measurements on the recombinant protein expressed by bacteria or transfected manimalian cells and by gene inactivation studies. For
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hypocretin, an excitatory neoromodulatory peptide that is produced by a few thousand hypothalamic neurons, that has been implicated in multiple homeostatic systems, including sleep and feeding, and that is implicated in all human narcolepsies, and for cortistatin, a somatostatin-like sleep-promoting peptide of cortical inhibitory intemeurons, we will generate lines of transgenic mice that express the intracellular portions of either diphtheria toxin or cholera toxin and thus either ablate or hyperactivate the neurons that normally produce these peptides. The hypocretin-DT mice will serve as a model for HLA-linked narcolepsy, which is thought to be caused by autoimmune destruction of hypocretin neurons. We will isolate RNA from these several transgenic mouse lines and use TOGA to identify the entire ensemble of mRNAs that are selectively expressed in hypocretin and cortistatin neurons. We will characterize knockout mice with null alleles in the genes encoding: a) 5-HT7, a serotonin receptor expressed prominently in ventral hypothalamus, which is coupled to stimulation of adenylyl cyclase, and whose pharmacology we have shown to be uniquely consistent with that of the 5-HT receptor that mediates circadian phase shifts in hypothalamic slice preparations, and which is a target for the sleep-promoting effects of oleamide, b) RC3/neurogranin, a forebrain-specific calmodulin-binding phosphoprotein which has been implicated in determining the availability of calinodulin and the calcium set point in dendritic spines and possibly in the development of dendritic spines, and c) cortistatin, a neuropeptide of cortical intemeurons that antagonizes the desynchronizing effects of acetylcholine on paired pulse and EEG measurements and enhances slow wave sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GHB ABUSE--CHEMISTRY AND NEUROBIOLOGY 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 26-SEP-2001; Project End 31-JUL-2004 Summary: Gamma-Hydroxybutyric acid (GHB) occurs endogenously in the brain where it is thought to be a neurotransmitter. GHB is used clinically for treating alcoholism and narcolepsy and is used non-medicinally, both as a primary drug of abuse (presumably because of its sedative/hypnotic effects) and as a sedating agent in unsuspecting victims (e.g., "date rate drug"). Despite GHB having been described more than 30 years ago and despite its widespread use, both medicinally and non-medicinally, relatively little is known about the mechanism that mediates the various effects of GHB. A GHBassociated binding site has been reported, although it is not known whether this site mediates the abuse- related effects of GHB. The paucity of information on the mechanism(s) of action of GHB results from a very limited set of relevant compounds that are available for studying this neurobiologic system and the absence of pharmacologically selective and validated neurochemical and behavioral procedures for characterizing the effects of GHB and related compounds. To that end, the studies proposed in this application will first characterize the receptor binding and behavioral effects of GHB and related compounds. Second, these studies will design and synthesize new compounds for studying the pharmacology of GHB. The working hypothesis of these multidisciplinary studies is that the behavioral effects of GHB are due to its actions on specific sites in brain that are not related to either GABAA or GABAB receptors. Studies under Specific Aim I will design and synthesize potent and selective agonists and antagonists for GHB receptors. Specific Aim II will characterize the binding of GHB and other compounds, including compounds that are synthesized under Specific Aim I, to specific sites in rat brain that have been characterized by our group with [3H]NCS-
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382. The functional consequences of GHB binding will be examined under Specific Aim III, including a characterization of the effects of GHB and other compounds on schedulecontrolled behavior and an evaluation of discriminative stimulus effects of GHB. These systematic characterizations of the binding and behavioral effects of GHB and the development of newly-synthesized compounds for GHB receptors will provide important new information regarding the mechanisms that mediate effects of GHB and related compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GHB EFFECTS ON EXTRACELLULAR DOPAMINE Principal Investigator & Institution: Walker, David; Pharmacology and Cancer Biology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Illicit use of gamma-Hydroxy butyrate (GHB), a popular new "club drug," has reached mini-epidemic levels in America. GHB is also in clinical trials for treatment of narcolepsy and alcohol addiction. GHB is pharmacologically unique among drugs of abuse because it is a naturally occurring substance in mammalian brain with its own receptor(s) and uptake system. Although reports of GHB abuse are rising rapidly, information about the interactions of GHB with the central dopamine systems that mediate drug reward and craving is conflicting. The purpose of the present proposal is to determine the effect of GHB on extracellular dopamine concentrations in awake rats using fast scan cyclic voltammetry. We will: (1) Determine dose- response relationships for the effects of GHB on electrically-stimulated dopamine concentrations in the caudate and the shell of the nucleus accumbens and resolve its effects on dopamine release and uptake kinetics, (2) Determine if repeated GHB exposure modifies the regulatory mechanisms that govern extracellular dopamine concentrations and alters the acute response to GHB. This research will study five doses of GHB that reflect human doses ranging from therapeutics to abuse. I hypothesize that low doses of GHB will increase dopamine release slightly in the caudate and nucleus accumbens and that high doses will robustly elevate dopamine release in both regions. These studies will utilize gastric administration of GHB in awake rats to provide realistic information about GHB effects on central dopamine neurotransmission Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOCRETIN NEURONS Principal Investigator & Institution: Van Den Pol, Anthony N.; Professor; Neurosurgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 15-DEC-2001; Project End 30-NOV-2006 Summary: Hypocretin (orexin) is a recently discovered neuropeptide synthesized by lateral hypothalamic area neurons that project widely throughout the brain and spinal cord. Functionally, hypocretin may play a key role in activation of many brain circuits related to attention, waking, or arousal. Absence of hypocretin or its hypocretin-2 receptor causes narcolepsy, a clinical condition characterized by short unexpected periods of sleep, both in animals and humans. A growing number of functional studies have shown that hypocretin may also modulate feeding, influence neuroendocrine neurons, alter blood pressure, and cellular physiology of the hypocretin cells. To facilitate the study of hypocretin neuron neurophysiology, we will use transgenic mice that express green fluorescent protein selectively in live hypocretin-acid transmitter will be studied with whole cell recording in cultured neurons and in hypothalamic slices. To
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facilitate the study of hypocretin neuron neurophysiology, synthesizing neurons. The hypothesis that hypocretin cells use glutamate as a primary fast-acting amino acid transmitter will be used with whole cell recording in cultured neurons and in hypothalamic slices. Hypocretin projects originating in the LH are found throughout the brain, including a dense local projection to the LH area where hypocretin axons make synaptic contact with hypocretin neurons. The hypothesis that hypocretin may excite hypocretin cells, potentially serving a positive feedback role in modulation of hypocretin cells, potentially serving a positive feedback role in modulation of hypocretin cells and pre-synaptic modulation of GABA and glutamate axons that innervate hypocretin neurons will be studied. Active and passive membrane properties of hypocretin neurons, concentrating hormone (MHC) is the other major neuropeptide found in cells interspersed with hypocretin neurons in the LH area. The hypothesis that MHC neurons make synaptic contact with hypocretin neurons in the LH area. The hypothesis that MCH neurons make synaptic contact with hypocretin, homeostasis, and may be the glucose-sensitive neurons of the LH, will be examined. Together, these experiments will provide a better understanding of the cellular mechanisms underlying hypocretin actions and neuronal communication to and from hypocretin neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOCRETIN RELEASE IN DISEASE STATES AND BEHAVIOR Principal Investigator & Institution: Siegel, Jerome M.; Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: Recent work in our laboratory has indicated that a degenerative loss of hypocretin (orexin) neurons underlies most cases of human narcolepsy. Several chronic diseases have symptomatic similarities to narcolepsy. This suggests that they may share abnormalities in the operation of the hypocretin (Hcrt) system. For example, patients with unipolar depression and schizophrenia exhibit REM sleep at sleep onset, one of the defining characteristics of narcolepsy. Nighttime sleep is frequently disrupted in both disorders, as in narcolepsy. The age of onset of both of these disorders is similar to that of narcolepsy. Many patients with schizophrenia have hallucinations resembling the hypnagogic hallucinations of narcolepsy. Alzheimer's disease, like narcolepsy, is characterized by daytime sleepiness and nighttime sleep disruption. This "sundowning" and related hallucinatory mentation is the most frequent cause of institutionalization. We have developed a far more sensitive assay for Hcrt than that used in prior published studies and have access to a large number of cerebrospinal fluid (CSF) samples from these three groups of patients and suitable controls. We will determine if low Hcrt levels are unique to narcolepsy or if they are present in one or more of these other disorders. We will determine if an Hcrt blood test can be developed to detect narcolepsy. Such a test would have an enormous impact upon the diagnosis and treatment of sleep disorders and on sleep research in general. We will compare blood Hcrt levels in narcoleptics, sleep apneics, REM sleep behavior disorder patients and controls. In parallel animal studies, we will determine the effect of behavior, including motor activity, feeding and short term sleep deprivation upon CSF Hcrt levels. Finally, we will use in vivo microdialysis to determine the pattern of Hcrt release in locus coeruleus, hypothalamus and ventrolateral preoptic area across the sleep wake cycle. We will contrast release patterns in active vs. quiet waking and REM vs. nonREM sleep. These studies will help define the role of this newly identified neurotransmitter system in relation to motor behavior, the sleep wake cycle and in human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOCRETIN SYSTEM IMMUNE DIATHESIS IN HUMAN NARCOLEPSY Principal Investigator & Institution: Black, John L.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: (adapted from applicant's abstract) Background and Health Relatedness: Narcolepsy is a disease that causes excessive sleepiness and abnormal regulation of REM sleep. The condition is chronic, debilitating, and detracts from quality of life. It is linked to a defect in the hypocretin (orexin) neurotransmission system in humans, dogs with hereditary disease, and mice. The cause of human narcolepsy is unknown. Human narcolepsy is associated with HLA DQB1*0602, is rarely familial, and has been associated with a mutation in only one case to date. Hypotheses: 1) HLA DQB 1 *061J2 positive humans with narcolepsy have serum and/or CSF antibodies reactive to one or more of the five components of the hypocretin neurotransmission system or hypocretin secreting cells. 2) Immunizing rats with the components of the hypocretin neurotransmission system will produce experimental autoimmune narcolepsy, which will mimic human narcolepsy and the narcoleptic symptoms seen in other animal models for the disease. Specific Aims: 1) Use ELISAs and IPAs to study the sera and CSF of HLA DQB1*0602 positive narcolepsy patients with cataplexy (including child and ethnically and gender diverse samples) to find antibodies reactive with preprohypocretin, hypocretin 1 and 2, and hypocretin receptor 1 and 2. Conduct Western blots and immunofluorescence studies with serum and CSF samples to determine antibody reactivity to cadaveric normal hypothalamus (known to be rich in the five known components of the hypocretin system) and transfected HEK 293 cells expressing the known components of the hypocretin neurotransmission system. Positive sera and CSF will also be preadsorbed and the studies will be repeated to determine if antibody specificity for these proteins exists. Results will be correlated between CSF and serum and epitope mapping will be done using positive sera. 2) Establish an experimental autoimmune animal model for narcolepsy by actively immunizing rats with recombinant preprohypocretin and hypocretin receptor 1 and 2 protein and by immunizing rats with plain and KHL-conjugated synthetic hypocretin system proteins and peptides. Passively immunized rats using polyclonal antibodies and purified antibodies will similarly be studied. Long term objectives: This translational, multidisciplinary research will demonstrate fundamental insights into the cause of narcolepsy and will open avenues for new interventions and preventative measures for this debilitating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOCRETINS AND THEIR ROLE IN THE CONTROL OF SLEEP Principal Investigator & Institution: Maki, Richard A.; Senior Staff Scientist; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2003 Summary: DESRIPTION: (Adapted from the Applicant?s Abstract) Insomnia is one of the more prevalent sleep disorders in the US, affecting about 10 percent of the population. Other sleep disorders include obstructive sleep apnea, restless leg syndrome and narcolepsy. Recently, a mutation in the G-protein coupled receptor hypocretin receptor-2 has been linked to the development of narcolepsy in dogs. In addition, the disruption of a gene in mice for the neuropeptide hypocretin led to the development of narcolepsy in those mice. These two results have focused attention on the hypocretin
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system as an important modulator of sleep in humans. The applicant organization, Neurocrine Biosciences, has developed a series of small molecule antagonists to the hypocretin receptor-2. The focus of this application is to first characterize these small molecule antagonists in vitro. The antagonists will be tested in competitive binding assays and cell-based functional assays. Second, the small molecule antagonists will be tested in vivo. Both rat and dog models will be set up and evaluated for the effect of the small molecule antagonists on sleep and wakefulness. The specificity of the effects of the small molecule antagonists will be further evaluated by comparing normal dogs with hypocretin receptor-2 mutated narcoleptic dogs. The results of this study will be valuable in determining the effectiveness of a hypocretin receptor antagonist in the control of sleep. These studies will also help to prepare the groundwork for the future development of hypocretin receptor-2 agonist as a possible treatment for narcolepsy. PROPOSED COMMERCIAL APPLICATION: A potential application for the research proposed is in the field of insomnia (an estimated 10% of the population suffers from chronic insomnia). Based on the available data, it is reasonable to hypothesize that hypocretin receptor antagonists will promote non-REM and REM sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOTHALAMIC CONTROL OF LIMB MOVEMENT Principal Investigator & Institution: Krilowicz, Beverly L.; California State University Los Angeles 5151 State University Dr Los Angeles, Ca 90032 Timing: Fiscal Year 2001 Summary: Understanding the neural regulation of behavioral arousal and motor facilitation is important to understanding the normal control of sleep- wake regulation and control of motor output, as well as elucidating the basis of such clinically relevant conditions such as insomnia, excessive day time sleepiness, rapid-eye movement behavior disorder and narcolepsy. Consequently, the long-term objective of this research program is to understand the role of the posterior hypothalamus in the control of sleep and arousal. The experiments included in the proposal are designed to determine which neurotransmitter systems are involved in posterior hypothalamic regulation of both cortical and behavioral (motor) arousal. They are designed to test the following hypotheses. 1) The cortical desynchrony and behavioral activation associated with electrical microstimulation of the posterior hypothalamus is due to activation of cell bodies and not fibers of passage. 2) Glutamate release into the posterior hypothalamus stimulates both cortical and behavioral components of arousal. 3) Histamine release into the posterior hypothalamus stimulates both critical and behavioral components of arousal. A secondary objective of this proposal is to introduce students to biomedical research. Consequently, the experiments have been designed to allow substantial student involvement. The research proposed will introduce students to the clinically important field of sleep research, as well as basic neurobiological techniques. The techniques and skills the students acquire will provide a sound base for and stimulate interest in more advanced training in the biomedical sciences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPACT OF SLEEP DISORDERS ON HEALTH Principal Investigator & Institution: Kryger, Meir H.; University of Manitoba Winnipeg R3t 2N2, Canada Winnipeg, Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003
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Summary: Sleep disorders are very common. The impact of these disorders on a person's long term health is unclear. The purpose of this project is to determine the cost to the health care system of patients with untreated sleep disorders and then to determine the change in cost with diagnosis and treatment. Hypotheses: Untreated sleep disorder patients (with sleep apnea, narcolepsy, and insomnia) are heavier consumers of health care services than age and sex matched controlled subjects and treatment will reduce these costs. Aims: The applicant will examine healthcare utilization data (and what patients were being treated for) of a large number of patients five years before diagnosis and five years after diagnosis and compare them to controls matched by age, gender, and postal code. The data will be obtained in a community with unrestricted access to medical care and where all the data is stored on a central database. To measure the use of medical services the applicant will analyze all doctors' claims and data from all hospitalization as well as use of prescription drugs. The applicant will establish whether treatment of these disorders reduces the consumption of healthcare services in these patients. The applicant expects to find fewer physicians visits, particularly for cardiovascular disease, neuro-psychiatric disease and general medical evaluations and for sleep apnea, fewer hospitalizations, particularly for cardiovascular disease and respiratory failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LOCUS COERULEUS AND RAPHE ACTIVITY IN SLEEP AND WAKING Principal Investigator & Institution: Eiland, Monica M.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: (adapted from applicant's abstract): Phylogenetic comparisons between mammals and reptiles could provide important clues to the function of sleep. Features of sleep, aminergic activity and cholinergic activity common to the reptilian, avian, and mammalian lines are likely to have been present in the stem reptiles. In mammals, the adrenergic cells of the locus coeruleus (LC) and the serotonergic cells of the raphe are tonically active in waking, decrease discharge in non-REM sleep, and are silent in REM sleep. Mammals also possess two cholinergic cell populations that produce the tonic and phasic components of waking and REM. The function or evolutionary history of these discharge profiles is not known. Narcolepsy, depression and REM sleep behavior disorder may result from disturbance of these discharging profiles. Though these immunohistochemically-defined populations are also found in reptiles, their activity has not been recorded in unanesthetized reptiles. The investigators have developed methods for recording brainstem units from a reptile, the common box turtle, Terrapene Carolina, during sleep and waking behaviors. They will identify and characterize the locus coeruleus, raphe, and cholinergic cell groups of the pedunculopontine and laterodorsal tegmentum immunohistochemically and electrophysiologically. They will compare these cells' state-dependent unit activity with that of mammals in order to provide insights into mthe evolutionary significance of sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MANAGEMENT OF EXCESSIVE DAYTIME SLEEPINESS IN NARCOLEPSY Principal Investigator & Institution: Rogers, Ann E.; Associate Professor; None; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
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Timing: Fiscal Year 2001; Project Start 10-FEB-1997; Project End 31-JAN-2003 Summary: (Adapted from investigator's abstract) Many of the psychological and economic consequences of narcolepsy can be directly attributed to sleep attacks and excessive daytime sleepiness. Uncontrollable episodes of daytime sleep make driving difficult or hazardous, affect the individual's ability to continue an education and pursue a career, and often interfere with interpersonal relationships. Although treatment of narcolepsy can improve symptoms dramatically in some patients, up to a third of patients with narcolepsy obtain little or no benefit from current therapies. Studies have shown widespread dissatisfaction with current pharmacologic treatments; some patients report being undermedicated, that their symptoms are not adequately controlled with stimulant medications, and that they are not satisfied by with treatment regimes that require daytime naps and/or drug holidays. Differences between responders and non-responders and the bases for those differences are unknown. In addition, the identification of patients who are less likely to respond to stimulant medications, will allow clinicians to concentrate more efforts on improving treatment regimes for these patients. The identification of an instrument that is reliable, sensitive to treatment effects, and easy to administer would be of great value for assessing patient's responses to treatment. Thus, the aims of this proposed multicenter study are to: 1) Develop profiles of those patients who respond to stimulant medications and those who do not respond; and 2) evaluate two brief questionnaires (Narcolepsy Symptom Status Questionnaire and Epworth Sleepiness Scale) to see if they can be used to assess treatment efficacy in a clinical setting. Two groups of narcoleptic subjects (135 established patients and 85 newly diagnosed patients) will be recruited from 5 accredited sleep disorders centers. A profile of subjects who respond to stimulant medications and those who do not will be developed from demographic data, symptom severity measures, and 24-hr ambulatory polysomnographic recordings made in the subject's usual environment. Compliance with stimulant medications will also be evaluated. In order to evaluate whether or not the NSSQ and ESS are sensitive to treatment effects, newly diagnosed subjects will be tested prior to starting stimulant medications, after 3 months of treatment and after one year of treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR AND BIOCHEMICAL ANALYSIS OF THE CANINE MHC Principal Investigator & Institution: Wagner, John L.; Associate Professor; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2003 Summary: (Adapted from the applicant's abstract): Canine models of human diseases have been used to study autoimmune thyroiditis, gluten-sensitive enteropathy, narcolepsy, complement deficiencies, and solid organ and hematopoietic progenitor cell transplants. Of paramount importance to comprehending immune-related diseases and transplantation immunology is an understanding of the MHC. In spite of the dog's usefulness in research, molecular and biochemical analyses of the canine MHC (termed DLA) have lagged behind those of the human MHC (HLA) and the murine MHC (H2) regions, as well as the MHC regions of various agricultural animals. The objective of this application is to develop a comprehensive understanding of the structure, polymorphism, and function of the canine class I and class II MHC genes. The specific goals are: 1) develop a DNA-based histocompatibility typing system for polymorphic class I and class II loci applicable to all dogs; 2) determine the structure and organization
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of the canine MHC by molecular mapping; and 3) identify tissues expressing class I proteins using newly generated monoclonal antibodies (MAbs). Histocompatibility typing for class I and class II genes will be performed using locus specific amplification and separation of alleles by single-strand conformational polymorphism (SSCP) gels. Pulsed-field gel electrophoresis (PFGE) with locus-specific probes will be used to determine the molecular organization of the DLA class I and class 11 gene families. A cosmid library will be constructed from a canine-hamster hybrid cell line containing a few dog chromosomes, one of which contains the DLA region. This library will be useful for mapping as well as identifying new genes within the DLA region. Class I expression will be analyzed at the protein level. Cell lines expressing canine class I genes will be produced, and reactive MAbs generated to be used in fluorescent activated cell sorting (FACS), immunoprecipitation, and immunohistochemistry studies. Class II expression will be initially studied using existing cross-reactive MAbs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUSCARINIC RECEPTOR COUPLING TO INOSITIDES IN CNS Principal Investigator & Institution: Fisher, Stephen K.; Professor; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-SEP-1986; Project End 30-NOV-2002 Summary: Alterations in muscarinic receptor neurotransmission in the central nervous system have been observed in Alzheimer's disease, narcolepsy, affective disorders, Parkinsonism and as a consequence of aging. As a result, significant effort has been expended in the design and development of muscarinic ligands that might be of potential therapeutic value. To date, five subtypes of muscarinic cholinergic receptors (mAChRs) have been described, three of which (m1, m3, m5) couple to a phosphoinositide-specific phospholipase C, with the attendant formation of inositol trisphosphate and diacylglycerol. Knowledge of the mechanisms underlying the regulation of mAChRs is important for evaluating the role played by mAChRs in signal transduction and in the rational design of therapeutic agents that could target this signaling pathway. In this proposal, we plan to extend our ongoing studies of the regulation of mAChR signaling to phosphoinositide turnover by examining the molecular mechanism underlying agonist-induced internalization of the receptor in human SH-SY5Y neuroblastoma cells. Specifically, the hypothesis to be tested is that the activity of phosphatidylinositol 4- kinase (PI4K), is an absolute requirement for the occurrence of receptor endocytosis. We will evaluate this hypothesis by the following approaches. By pharmacological means, we will determine the ability of known inhibitors of PI4K to inhibit mAChR endocytosis. By means of biochemical, immunological and cell biological approaches, we will determine the specific isoform(s) of PI4K that are involved in receptor endocytosis and their site of action within the endocytic cycle. To evaluate cause and effect, molecular genetic approaches will be employed to examine the effects of depletion and over-expression of PI4K on the extent of receptor internalization. Although phosphoinositides have been implicated in membrane trafficking events, most emphasis has been placed on the 3'phosphoinositides. The present proposal focuses on the potential role played the quantitatively major 4'-phosphoinositides in this process, evidence for which is beginning to accumulate in both normal and pathological states. This proposal presents strong preliminary evidence linking PI4P synthesis to the internalization of mAChRs. It is likely that the knowledge gained from these studies will be of fundamental
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importance to understanding the regulation of cell signaling events in neural cells initiated not only by mAChRs, but also by other G-protein coupled receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NARCOLEPSY--MULTICENTER GENETIC AND FAMILY STUDY Principal Investigator & Institution: Henriksen, Steven J.; Member; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 31-MAY-2004 Summary: Narcolepsy, as presently understood, is a central nervous system disorder characterized by disabling dysregulation of sleep and wakefulness. Narcolepsy is not rare and afflicts about 1 of every 1000 to 2000 North Americans. While the inheritance of narcolepsy is not known, the disorder is strongly, but NOT always, associated with subtypes of the HLA region chromosome 6 [HLA-DR15(DRB1*1501) and HLADQ6(DQBl*0602)]. Thus, the presence of HLA-associated and non-HLA associated forms indicates that narcolepsy is at least two disorders. Further, both the HLA associated (H+) and the non-HLA associated ( H - ) form occur as sporadic isolated cases (F-) and family history positive cases. It is possible that each of the four types, (H+F),(H+F+), (H-F-), (H-F+) represent different etiologies. This Multi-Center Clinical Study grant is based on several key findings: (a) the strong association with the same HLA alleles across several populations indicates a probable role for these alleles/haplotypes, ( b ) only 70 percent of the probands with narcolepsy have the HLA-associated alleles and they tend not to have affected relatives, (c) the majority of families with multiple affected members do not have the associated HLA haplotypes, (d) one pair of MZ twins differs with respect to clinical symptoms, with/without cataplexy, and (e) sleep studies of first degree relatives of probands reveal subtle sleep disturbances. Our overall goals are: (i) Ascertain an additional 113 probands and their families via a sequential sampling scheme which requires that all patients selected as probands meet the strict clinical criteria for narcolepsy (ignoring HLA type) and that all first degree relatives of probands be studied. Rigorous sampling in this manner avoids bias due to selecting "interesting" families and permits accurate evaluation of the proportion of narcoleptics patients with the associated HLA types, segregation analysis for narcolepsy and the related clinical subtypes, as well as linkage analyses. (ii) Identify the modes of inheritance for the two familial forms of narcolepsy. Determine the familial aggregation and inheritance of the related sleep disorder symptoms (e.g., excessive daytime sleepiness). (iii) Using both the proband series families and selected "high density" pedigrees, map the location of the non-HLA associated familial form via a genome DNA marker screen and linkage analyses. (iv) Examine the role of the HLA-associated alleles in narcolepsy through both co-segregation and association studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROBIOLOGY OF OREXIN/HYPOCRETIN-INDUCED AROUSAL Principal Investigator & Institution: Berridge, Craig W.; Professor; Psychology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 04-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant): Orexins are a newly identified peptide family comprised of two peptides, orexin-A and orexin-B, which are synthesized by a limited population of neurons located within the lateral and dorsal hypothalamus. Initially, these peptides were demonstrated to stimulate feeding, when administered in relatively high doses. However, orexin neurons project widely throughout the brain and spinal
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cord, including to regions associated with the regulation of behavioral state. Consistent with these observations, substantial evidence suggests dysregulation of orexin neurotransmission is associated with the sleep/arousal disorder, narcolepsy. Further, recent evidence suggests that these peptides exert an activating influence on forebrain and behavioral state. In preliminary studies, the PI has observed potent arousalenhancing actions of orexin when administered into sleeping/resting animals, at doses substantially below those that elicit feeding. The neural mechanisms that underlie these arousal-enhancing actions remain unknown. Work by the PI demonstrates that the locus coeruleus (LC)-noradrenergic system exerts a potent activational influence on forebrain neuronal and behavioral activity states. These actions derive, in part, from actions of norepinephrine within a subset of basal forebrain structures. Given this, it is of interest that orexin-containing fibers innervate LC, these same basal forebrain structures, as well as other regions implicated in the regulation of behavioral state. The proposed studies will complete preliminary studies that characterize the dose-dependent effects of orexinA and -B on behavioral state. Additionally, these studies will characterize the anatomical organization of the orexin efferent projection system. Finally, these studies will provide initial assessment of a number of potential neural mechanisms underlying orexin-enhanced arousal. Specifically, the extent to which orexins alter behavioral state via actions within certain basal forebrain and brainstem structures will be examined. These studies will provide a better understanding of the neurobiology of orexin, the neurobiology of sleep and waking, and the potential role of orexin in narcolepsy and other disorders of arousal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPHARMACOLOGY OF AROUSAL AND SLEEP DISORDERS Principal Investigator & Institution: Nakajima, Yasuko; Professor; Anatomy and Cell Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The main objective of this research proposal is to investigate neuropharmacologically the cellular mechanisms of arousal and sleep with a special emphasis on the pathogenesis of narcolepsy. Hypocretins/orexins, newly discovered peptide neurotransmitters, and their receptors will be studied. Hypocretins/orexins and their receptors play a role in narcolepsy and sleep disorders and in the regulations of food intake. Currently little is known about their physiological effects on brain neurons. Previous studies have shown that lack of excitation produced by hypocretins/orexins through hypocretin2/orexin2 receptors in the brain nuclei is the central component of narcolepsy. Proposed projects focus on further elucidating their actions at the cellular and molecular level by using dissociated primary cultures of rat and mouse brain nuclei that are involved in regulating arousal and sleep. The specific projects are: (1) to elucidate hypocretin/orexin effects on histaminergic neurons in the tuberomammillary nucleus which are rich in hypocretin2/orexin2 receptors, (2) to determine the transmitter effects on noradrenergic neurons in the locus coeruleus which are rich in hypocretin1/orexin 1 receptors, and (3) to investigate hypocretin/orexin effects on cholinergic neurons in the nucleus basalis of Meynert. In addition, a heterologous system (HEK293A) which is transfected with each type of hypocretin/orexin receptor will be used. All of these projects emphasize elucidating signal transduction mechanisms of hypocretins/orexins, and determining the identity and roles of G proteins. Electrophysiological techniques (patchclamp) and pharmacological techniques combined with molecular biological methods will be used. These projects are important for deepening the understanding of narcolepsy and other
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sleep disorders. The knowledge obtained is essential in developing more effective treatments for narcolepsy and other sleep disorders. This research on the sleep-arousal centers of the brain will contribute in helping those who suffer sleep disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL MODAFINIL IN NARCOLEPSY Principal Investigator & Institution: Pack, Allan I.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 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: ORAL MODAFINIL VERSUS PLACEBO FOR THE TREATMENT OF NARCOLEPSY Principal Investigator & Institution: Wasleben, Joyce; New York University School of Medicine 550 1St Ave New York, Ny 10016 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: OREXIN AND THE CONTROL OF SLEEP AND WAKEFULNESS Principal Investigator & Institution: Mc Carley, Robert W.; Professor; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (applicant's abstract): Orexins/Hypocretins are newly discovered hypothalamic peptides that studies in canine inherited narcolepsy and mouse knock-out experiments link to cataplexy/narcolepsy, which may be regarded as disorders of REM sleep and wakefulness. Indeed, orexin neurons in the lateral hypothalamus have widespread projections to regions important in control of sleep and wakefulness. The broad objective of this program of research is to understand the physiological and pharmacological mechanisms by which orexin modulates behavioral state and thereby to provide a sound basis for the understanding and treatment of human sleep disorders, especially narcolepsy. The key techniques to be used are novel combinations of multidisciplinary methods including the use of microdialysis perfusion of antisense against mRNA of orexin receptors combined with electrographic recording of behavioral states, measurement of extracellular levels of orexin peptides using enzyme linked immunosorbent assay (ELISA), and a method combining extracellular single unit recording with microdialysis-delivered orexinA and B in freely behaving rats. Our broad hypotheses are that (1)orexin/hypocretin controls/regulates REM sleep and cataplexy via selective action on brainstem neurons, primarily those in the nucleus subcoeruleus alpha, and that this action is mediated by the orexin II receptor; and (2)that orexin/hypocretin regulates wakefulness through the forebrain sites of the cholinergic basal forebrain and tubero-mammillary nucleus (TMN), with mediation by the orexin II receptor. Microdialysis perfusion of antisense against the mRNA of orexin receptors will be used to reduce the levels of orexin receptors, producing a "reversible knockout." We will test the hypothesis that, in accord with our preliminary data, orexin-B has a major effect on REM-related phenomena via orexin type II receptors in the subcoeruleus region of the pontine reticular formation, and that antisense to this receptor will increase
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muscle atonia and the REM phase of sleep, as well as cataplexy. We hypothesize that orexin acts via type I receptors in the locus coeruleus and dorsal raphe, predicting that antisense to type I receptors will increase REM sleep but not cataplexy. Conversely, we predict that microdialysis application of orexin B and A (relatively selective for type I receptors) respectively to these regions will decrease REM sleep. Microdialysis applications of antisense and orexin-B in brainstem muscle inhibitory pathways will test for the presence of predicted orexin modulatory effects on cataplexy. For mesopontine cholinergic neurons, we predict that orexin-B mediates arousal via activating neurons preferentially active in both wakefulness and REM sleep, and this will be tested via microdialysis-applied orexin-B combined with unit recording. In the forebrain, we hypothesize that orexin promotes wakefulness by excitatory actions on basal forebrain and histaminergic neurons preferentially active in this state, and modulated by orexin II receptors, a hypothesis supported by our preliminary data on basal forebrain microdialysis perfusion of orexin peptide. In experiments whose logic parallels those in the brainstem (but with wakefulness as the primary variable), we will use perfusion of antisense, orexin-B and electrographic and unit recording to test this hypothesis. Throughout all brainstem and forebrain sites, we predict that the extracellular levels of orexin-A will be highest during the dark (active) phase compared with the light phase and orexin-B will be highest in wakefulness as compared to non-REM phases of sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES BIRMINGHAM
OF
SLEEP
DISORDERS
IN
OLDER
MEN-
Principal Investigator & Institution: Lewis, Cora E.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with
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an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES MINNEAPOLIS
OF
SLEEP
DISORDERS
IN
OLDER
MEN-
Principal Investigator & Institution: Ensrud, Kristine E.; Associate Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OUTCOMES OF SLEEP DISORDERS IN OLDER MEN-PALO ALTO Principal Investigator & Institution: Stefanick, Marcia L.; Associate Professor of Medicine; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OUTCOMES OF SLEEP DISORDERS IN OLDER MEN-PORTLAND Principal Investigator & Institution: Orwoll, Eric S.; Professor of Medicine; Endodontology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men,
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will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERIODIC LIMB MOVEMENTS IN WILLIAMS SYNDROME Principal Investigator & Institution: Mason, Thornton B.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Candidate's Plans/Training: The candidate plans a career as a patient-oriented researcher bridging pediatric medicine, sleep disorders, and genetics. Training will include formal epidemiology and biostatistics course work, structured laboratory work, and closely mentored completion of the research protocol. Environment: The outstanding pediatric research setting at UPCHP includes expertise in sleep disorders, clinical genetics, and molecular biology. These areas of strength will be complemented by the clinical and basic science research support offered by the Center for Sleep and Respiratory Neurobiology. Pennsylvania's Center for Clinical Epidemiology and Biostatistics will provide formal course training. Collectively, the environment is uniquely suited for this training award. Research: PLMS are rhythmic and highly stereotyped flexion movements of the extremities. PLMS may produce significant sleep disruption, and occur over a range of patient ages and settings. The pathophysiology of PLMS is unknown. Although family studies suggest a genetic basis for some cases of PLMS occurring with restless legs syndrome, no associated genes or gene products have been identified. Because preliminary data support the paucity of PLMS among control subjects and the prominence of PLMS in children with WS, this special group of patients may represent a unique opportunity to allow identification of a gene(s) involved in PLMS. WS is a human developmental disorder caused by a microdeletion of multiple genes in a distinct region of chromosome 7 (7q11.23). In this protocol, I propose to test the specific hypothesis that children with WS manifest genetically determined PLMS that is responsive to dopaminergic therapy. To this end,
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the primary aims of this proposal are: 1) to determine the prevalence of PLMS and the degree of variability in children with WS; 2) to determine whether PLMS are sensitive to dopamine therapy as are PLMS to other populations; and 3) to determine if there is a specific PLMS-genotype correlation in patients with WS. This protocol will provide new insights into WS as a model for PLMS in the general population, and may identify a specific gene(s) implicated in the etiology of these movements. Further, it will provide training necessary to conduct rigorous patient-oriented research in the area of genetics of sleep and its disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGICAL STUDIES OF HUMAN AND CANINE NARCOLEPSY Principal Investigator & Institution: Nishino, Seiji; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 15-JUL-1998; Project End 30-JUN-2003 Summary: (Applicant's abstract): This proposal is a request for a K01 Mentored Research Scientist Development Award. The candidate is a neuropsychiatrist who is experienced in neurochemistry and neuropharmacology. The candidate proposes to gain experience in clinical and basic neuropharmacology. His goal is to develop better pharmacological treatments for human narcolepsy. Human narcolepsy is a sleep disorder affecting 0.050.16% of the general population. The objective of this proposal is to dissect the neurochemical control of sleep in narcolepsy using a pharmacological approach and to apply this knowledge to improve the treatment for human narcolepsy. This will not only benefit narcoleptic patients but also provide critical information on the neurochemical mechanisms generating normal sleep. The research is greatly facilitated by the use of a unique animal model of narcolepsy in which the condition is transmitted as a fully penetrant autosomal recessive trait. In the past several years, the candidate has focused on the pharmacological control of canine cataplexy, a pathological manifestation of REM sleep atonia. The results indicate that this symptom, as REM sleep, is mainly controlled by cholinergic and monoaminergic systems. Several receptor subtypes that mediate this neuropharmacological control (muscarinic M2, adrenergic alpha-lb and alpha-2/D2(3)) have been identified. In this award period, the candidate will: (1) apply the knowledge that the adrenergic system is the most important monoaminergic system for the control of cataplexy obtained using the canine model to improve the treatment of human cataplexy, (2) test the hypothesis that the wakepromoting effects of amphetamine-like compounds are mediated via presynaptic stimulation of the dopaminergic transmission by attempting to correlate the in vivo effects on sleep and in vitro binding affinities for dopamine transporter site, in vitro potencies of dopamine uptake inhibition and in vivo effects on dopamine efflux of various wake-promoting compounds, and (3) determine the sites of action of wakepromoting compounds. This will involve local drug injection and in vivo microdialysis experiments. As preliminary results suggest the involvement of the mesolimbocortical dopaminergic system in narcolepsy, the candidate will principally focus on this anatomical system. Results from the canine model concerning excessive sleepiness could also apply to human narcoleptics at a later stage. With this Research Scientist Development Award, the candidate will contribute to the development or better pharmacological treatments of human narcolepsy while also furthering the candidate's career objective to be an independent scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRIMARY SLEEP DISORDERS IN HYPERACTIVE CHILDREN Principal Investigator & Institution: Chervin, Ronald D.; Associate Professor and Director; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2003 Summary: Hyperactive behavior (HB) is a vexing problem for a large number of children with and without a formal diagnosis of attention- deficit/hyperactivity disorder (ADHD). Although the causes of HB are poorly understood, one such cause may be primary sleep disorders; the small subset of children seen at sleep centers often have HB that resolves when a sleep disorder is identified and treated. Arising from this observation, the long-term objective of this application is to examine the impact of undiagnosed sleep disorders on HB in children. The research plan starts with a crosssectional survey of 1000 patients at a general pediatrics clinic to test for associations between HB and symptoms of sleep disorders in children aged 2-14 years. Subjects thus found to be hyperactive will be tested to establish the frequency of sleep disorders. A randomized controlled clinical trial will then be performed to determine whether HB improves when children's sleep disorders are treated. Finally, the cohort of children originally identified as being free of HB will be reassessed 4 years later to determine which symptoms of sleep disorder might predict later development of HB. The candidate for this research career award is a tenure-tract assistant professor in neurology with special expertise in sleep medicine who seeks to establish a clinical research career at the interface of the two disciplines. He plans to acquire additional expertise in children's sleep and behavior and to initiate prospective research in a promising new area. His long-term goals are to focus on neurological and behavioral effects of sleep-related breathing disorder to develop optimal standards and techniques for diagnosis of these conditions and to improve effectiveness of their treatment. To foster these goals, the University of Michigan offers internationally recognized colleagues and state-of-the-art facilities for pediatric polysomnography. The Department of Neurology provides an unwavering commitment to the development of the P.I. has an independent investigator, including funds for the candidate's graduate studies at the School of Public Health in clinical research design and biostatistics (M.S. expected in May 1997). This training, combined with prior education in neurology and sleep disorders under distinguished clinicians and researchers, leaves the candidate willprepared for a successful independent research center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PUPILLOMETRIC SLEEPINESS IN TREATED SLEEP DISORDERS Principal Investigator & Institution: Merritt, Sharon L.; Medical-Surgical Nursing; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 15-MAY-2000; Project End 29-FEB-2004 Summary: Patients with obstructive sleep apnea and narcolepsy can experience a diminished quality of life, decreased productivity, and workplace and traffic accidents due to the pathologic excessive daytime sleepiness (EDS) associated with these disorders. Currently, the extent of EDS is determined by polysomnography and the Multiple-Sleep Latency Test (MSLT), two EEG-based physiologic sleepiness measures that are labor intensive, time-consuming, expensive and receive limited health insurance coverage. As people become sleepy, their pupils oscillate widely and decrease in size. In this study, the Pupil Unrest Index (PUI) will be calculated to estimate sleepiness using desk top pupillometry, an efficient, convenient, non-invasive and easily repeatable
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technique. The PUI quantitatively describes the extent of pupillary oscillation during 15 minutes of alertness testing. Quantitative data comparing the PUI to other physiologic sleepiness measures are not available. The subject cohorts for this repeated measures, known groups methodologic study will consist of normal controls, and obstructive sleep apnea and narcolepsy subjects before and after usual treatment. The specific aims are to (1) correlate the PUI with MSLT sleep latencies among the subject groups; 92) compare the PUI to the MSLT in detecting sleepiness among the three subject groups; and (3) compare the PUI and the MSLT to other objective and subjective sleepiness measures between subject groups, and before and after usual treatment among the OSA and narcolepsy subjects. MANOVA will be used to examine the linear relationship between the PUI and the MSLT among the subject groups, and the differences in measures of perceived sleepiness, sleep quantity, sleep quality and continuity, mood and functional status between the subject groups, and pre-post-treatment fore subjects with OSA and narcolepsy. The sensitivity and specificity of the PUI in detecting sleepiness will be estimated using the MSLT results as the "gold standard" for classifying subjects. MLR will be used to estimate the relationship between the PUI or the MSLT, and other objective and subjective sleepiness measures. Results will provide evidence about the PUI as a reliable and valid objective outcome measure of waking tendency among controls, and pre-post-treatment for OSA and narcolepsy subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RAT MODELS TO SCREEN COMPOUNDS INDUCING SLOW-WAVE SLEEP Principal Investigator & Institution: Bergmann, Bernard M.; Slowave 20 N Wacker Dr, Ste 2200 Chicago, Il 60606 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 30-JUN-2004 Summary: (provided by applicant): A main goal of SloWave, Inc. is to develop a novel class of sleep-enhancing compounds that, unlike all currently available hypnotics, stimulate slow-wave sleep (SWS), the deepest and most restorative stage of sleep. SloWave plans to develop structural analogs of a natural neuromodulator, gammahydroxybutyrate (GHB), which is a potent stimulant of SWS, and has a specific newly identified receptor system in the brain. The objective of this Phase II proposal is to synthesize and screen compounds with the most potent effects on SWS. The specific aims are: 1. To test about 50 GHB agonists, identified by binding assays to have affinity for the GHB receptor, for their ability to induce changes in locomotor activity and body temperature, and to later test about 10 of the lead compounds for their effects on EEG sleep-wake states. 2. To test important hypotheses concerning the mechanisms of action of GHB by examining the effects of various GABAergic or dopaminergic antagonists on GHB-induced alterations in behavioral or physiological state. 3. To determine the effect of chronic treatment with GHB on sleep, and to determine if withdrawal from chronic drug exposure leads to sleep disturbances. The completion of these studies will result in: 1. The identification of 2-3 novel compounds that will subsequently be tested for toxicity prior to human Phase I studies. 2. Increased understanding of the mechanisms of action of GHB on sleep information, which is critical for the design of clinical studies. 3. The definition of the effects of chronic GHB treatment on sleep information, which is important for later pre-clinical studies on the chronic effects of our compounds. The development of GHB related compounds will represent a major breakthrough in the treatment of conditions which involve decreased or abnormal slow-wave sleep, such as aging depression, fibromyalgia and narcolepsy, which together affects many millions of individuals. PROPOSED COMMERCIAL APPLICATION: SloWave will develop a novel
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class of sleep-enhancing compounds acting via the GHB system which, unlike currently available hypnotics, stimulate slow-wave sleep, the deepest and most restorative stage of sleep, and have a pharmacokinetic profile consistent with the maintenance of sleep and a heightened level of alertness upon awakening. These new compounds will represent a major breakthrough in the treatment of conditions and illnesses which involve disturbed sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP CONTROL BY THERMOSENSITIVE NEURONS Principal Investigator & Institution: Mcginty, Dennis J.; Adjunct Professor; Psychology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-1992; Project End 30-JUN-2005 Summary: (applicant's abstract): We propose to study neurophysiological mechanisms mediating the regulation of serotonin-containing neurons in the mammalian dorsal raphe nucleus (DRN) by the hypnogenic system in the preoptic hypothalamus and adjacent basal forebrain (POA/BF). Activation during spontaneous sleep of warmsensitive neurons (WSNs) and deactivation of cold-sensitive neurons (CSNs) plays a critical role in the POA/BF hypnogenic process. WSNs and CSNs are identified by responses to local warming and cooling. Previous evidence shows that the POA/BF also contains both REM-facilitatory and REM-inhibitory processes. Suppression of DRN serotonergic neuronal discharge was shown to play a role in both NREM sleep onset and REM sleep triggering. Recent anatomical and physiological evidence shows that activation of the POA/BF WSN/CSN hypnogenic system can induce suppression of DRN neuronal activity, suggesting a mechanistic basis for NREM-REM coordination. We have developed a testable 2-stage model of regulation of DRN and REM triggering by the POA/BF. Aim 1 is to quantify the regulation of REM sleep control by POA/BF temperature-sensitive neurons. Aim 2 is to use microdialysis to confirm that POA/BF warming induces increased release of the inhibitory neurotransmitter, gammaaminobutyric acid (GABA) in DRN, and that postsynaptic blockade of GABA in DRN prevents POA/BF-induced changes in NREM EEG deactivation and REM-triggering. Aim 3 will combine microdialysis and neuronal unit recording in the DRN to assess hypotheses that GABA release induced by POA/BF warming regulates DRN neuronal discharge and that DRN neuronal discharge regulates REM triggering. Aim 4 will use techniques to generate REM-enriched sleep and the method of proto-oncogene c-fos expression to label neuronal activity in order to assess a hypothesis that a subregion of the POA/BF, the peri-ventrolateral preoptic area (peri-VLPO) contains REM-selective neurons. Aim 5 is confirm the existence of REM-selective neurons in peri-VLPO using chronic neuronal unit recording techniques. Aim 6 is to use microdialysis of a GABA agonist, muscimol, to inactivate the peri-VLPO area to assess the hypothesis that this region is essential for REM-triggering. These studies will provide a new model of interactions of NREM and REM sleep mechanisms and will contribute to the understanding of human diseases including narcolepsy and affective disorder in which NREM-REM coupling is disordered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SLEEP IN PTSD/PANIC: A MULTIMODAL NATURALISTIC STUDY Principal Investigator & Institution: Sheikh, Javaid I.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305
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Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The past decade has seen exciting advances in our understanding of central fear systems, information regarding the extended amygdala, the broader limbic system, their targets and modulating structures, is providing new avenues for the formation of testable models of anxiety disorders that are amongst the most common psychiatric illnesses. Panic disorder (PD) and posttraumatic stress disorder (PTSD) are prime candidates for explication by reference to central fear systems. Further, because they converge and diverge in important ways, PD and PTSD challenge our understanding of how central fear systems can support related yet distinct anxiety syndromes. A strong version of this challenge is presented by the sleep disturbances of PD and PTSD. Both are associated with subjectively disturbed sleep continuity, nocturnal paroxysmal episodes (nocturnal panic attacks and trauma-related nightmares, respectively), and, our data would suggest, suppression of sleep movement. Nevertheless, these two anxiety disorders appear to exhibit divergent modifications of nocturnal respiration, elevated tidal volume variability in PD, versus accelerated respiration in association with nightmares in PTSD. The aim of this project is to lay the foundation for a more comprehensive account of the interaction of sleep and fear systems in PD and PTSD by optimally quantifying domains in which they converge and diverge: arousals from sleep, sleep movements and sleep respiration. In this study, sleep data will be obtained from 180 community-residents, unmedicated, female and male subjects with PD (30 with and 30 without a history of nocturnal panic attacks), PTSD (30 with and 30 without a history of trauma-related nightmares), comorbid PD and PTSD (30), and normal controls. The proposed methods represent an advanced approach to naturalistic sleep data acquisition, combining an initial phase of ambulatory polysomnography (PSG) with extended (21+days) actigraphy and auditory sonography. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP, AGING, AND THE HYPOCRETIN/OREXIN SYSTEM Principal Investigator & Institution: Kilduff, Thomas S.; Senior Director; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Sleep in the elderly is generally recognized as being of poorer quality than in younger adults. Nocturnal sleep in seniors is characterized by frequent awakenings, decreases in the quantity of deep slow wave sleep (Stages 3 and 4), and a concomitant decrease in delta frequencies in the EEG. Daytime alertness is reduced and naps are common, indicating diminution of the diurnal rhythms of sleep and wakefulness. Many of these changes in sleep architecture also occur in aged laboratory rodents. Our long-term objective is to understand the neural basis of agerelated sleep dysfunction. The hypocretin/orexin (H/O) neurotransmitter system has recently been identified as being important in arousal state regulation, and degeneration of the H/O neurons has been found in human narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Therefore, this system is an attractive target to study with respect to sleep and aging. The overall hypotheses of this proposal are that (1) the H/0 system is important in the maintenance of wakefulness; (2) a dysfunction of the H/O system occurs in the aged; and (3) this dysfunction is related to the sleep/wake disturbances characteristic of the elderly. Based on the literature, we conclude that aged rodents, like elderly humans, are a heterogenous population and differ with respect to their rate of physiological aging. Therefore, we will identify a subpopulation of aged rats having disrupted body temperature rhythms and sleep architecture and use these animals to test the following
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specific hypotheses: (1) an age-related decline occurs in the number of H/O cells in aged F344 rats that is correlated with disrupted sleep architecture; (2) an age-related decline occurs in the levels of H/O mRNA and/or peptides; (3) waking-related activation of H/O cells declines with age; (4) the release of H/O peptides decreases with age; (5) an age-related decline in the mRNA for the H/O receptor 1 and receptor 2 occurs in brain regions associated with wakefulness; and (6) an age-related decrease in binding to H/O receptor 1 and receptor 2 and/or G protein activation occurs in arousal-related brain regions. To address these questions, we will use a combination of in vivo physiological, neuroanatomical, molecular, and receptor pharmacological methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECTRUM OF NARCOLEPSY AND ITS SYMPTOMS Principal Investigator & Institution: Young, Terry B.; Professor of Prventative Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2002 Summary: The overall goal of the epidemiology study proposed here is to provide population-based knowledge on the occurrence and correlates of narcolepsy-related symptoms and polygraphic signs as a foundation for characterizing and refining the working definition of human narcolepsy. We propose the collection of new data from participants enrolled in the Wisconsin Sleep Cohort Study, a longitudinal epidemiology study of the natural history of sleep disorders. This will be established by: a) administering a narcolepsy-related symptom questionnaire to a sample of 5000 middleaged men and women; b) on a subsample of 820, conducting multiple-sleep latency tests (MSLTs) designed to detect episodes of sleep-onset rapid eye movement sleep periods (SOREMPs); and c) HLA typing to determine DQP1 positivity These new data will be added to extensive subjective and objective data on a sample of 1400, including baseline and follow-up polysomnography, experimental MSLTs, and other tests collected previously and currently as part of the Wisconsin Sleep Cohort Study. The anticipated results will be of direct application to the development of more specific and more sensitive guidelines for diagnosis and treatment of narcolepsy. In addition, the expected new knowledge on the spectrum and correlates of narcolepsy symptoms and signals will provide a foundation for further research on risk factors and adverse health outcomes on narcolepsy. The specific aims are: 1. To determine in the general adult population the distribution and correlates of narcolepsy-related symptoms (cataplexy, sleep paralysis, hypnagogic hallucinations, automatic behavior, excessive daytime sleepiness, and disturbed nocturnal sleep), and polygraphic signs including SOREMPs; 2. To confirm that HLA-DQ polymorphisms in the general population influence nocturnal sleep architecture; 3. To evaluate the influence of HLA susceptibility alleles on narcolepsy-related symptoms and signals, diagnostic groupings, and symptom clusters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STATE DEPENDENT CONTROL OF MOTORNEURON ACTIVITY Principal Investigator & Institution: Chase, Michael H.; Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1976; Project End 31-JUL-2005 Summary: Abnormal patterns of motor behavior are a key component of a number of sleep disorders. These patterns of behavior are evidenced, for example, during wakefulness by cataplectic attacks, in which the motor inhibition that normally occurs
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during active (REM) sleep is expressed during the waking state. On the other hand, there is a lack of motor inhibition during active sleep that occurs in disorders such as REM Sleep Behavior Disorder. These and various other sleep disorders that involve disrupted motor control during active sleep and wakefulness are the clinical bases for the proposed studies dealing with the paradoxical phenomenon of "reticular responsereversal," wherein a brainstem system exerts dual functions that are dictated by the ongoing behavioral state of the animal, i.e., motor activation during wakefulness (and quiet (NREM) sleep) and motor inhibition during active (REM) sleep. We hypothesize that hypocretin, a newly discovered peptide that has been implicated in the generation of narcolepsy/cataplexy, may be the neurotransmitter that is utilized by the system of reticular response-reversal. Our discovery that hypocretin- containing cells in the hypothalamus are active not only during wakefulness, but also during active (REM) sleep, together with our other preliminary studies demonstrating that hypocretin acts at various sites to promote motor activity during wakefulness and to enhance motor inhibition during active sleep, suggest that hypocretin may be the neurotransmitter that sustains this systems' actions at the level of motoneurons as well as supporting its circuitry within the brainstem. Our studies will provide fundamental data, which are currently non-existent, of a) the role of hypocretin in the in vivo control of neuronal (motoneuron) activity, which includes the spontaneous and synaptic drives which are fundamental to determining the activity levels of cells; b) the interaction of hypocretin, in vivo, with classical excitatory and inhibitory neurotransmitters; and c) the role of hypocretin, in vivo, in response-reversal in promoting the non-reciprocal excitation of motoneurons during wakefulness and the non-reciprocal inhibition of motoneurons during active sleep. These data will allow us to determine the veracity of our hypothesis that hypocretin plays a critical role in maintaining active sleep and its physiological components in addition to participating in waking functions and waking control mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SURVIVAL MODELS FOR MAPPING GENES FOR COMPLEX DISEASES Principal Investigator & Institution: Li, Hongzhe; Associate Professor; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2005 Summary: (provided by applicant): The long term objective of this project is to develop powerful and computationally efficient statistical methods of identifying genes underlying complex genetic diseases in humans. The specific aim of this project is to continue to develop survival models to incorporate age of onset data, environmental covariates information, gene-environment interactions, and multiple disease loci into family-based association analysis, joint linkage and linkage disequilibrium analyses, and multipoint multi-trait-locus linkage analysis of complex human diseases. The proposed methods build on our current methods and hinge on novel integration of methods in multivariate survival analysis and methods in modern human genetics. The focus will be on the development of survival models for: (1) incorporating age of onset and environmental risk factors into genetic association study using a linkage disequlibrium based Cox model for family data of any size; (2) joint analysis of linkage and linkage disequilibrium for age of onset data based on nuclear families; (3) for multipoint multitrait-locus linkage tests that can incorporate age of onset and environmental covariates data using the additive genetic frailty model. The project will also investigate the power and efficiencies of these methods, and compare them with existing methods. In addition,
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this project will develop practical and feasible computer programs in order to implement the proposed methods, to evaluate the performance of these methods through extensive simulations and application to real data on HLA-associated diseases, including type 1 diabetes, rheumatoid arthritis, celiac disease, narcolepsy, and ankylosing spondylitis. The work proposed here will contribute both statistical methodology to mapping genes for complex diseases and multivariate survival analysis, offer insight into each of the clinical areas represented by the various data sets to evaluate these new methods, and facilitate final identification of genes involved in these complex diseases. All programs developed under this grant and detailed documentations will be made available free-of-charge to interested researchers via the World Wide Web. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNAPTIC MODULATION OF MESOPONTINE CHOLINERGIC NEURONS Principal Investigator & Institution: Leonard, Christopher S.; Profesor; Physiology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-DEC-1991; Project End 31-JAN-2007 Summary: (provided by applicant): Chronic or intermittent sleep disorders such as narcolepsy, sleep apnea, and insomnia afflict nearly 40 million people in the United States. Yet the neural mechanisms controlling both normal sleep and its pathologies remain poorly understood. Considerable evidence indicates that mesopontine cholinergic neurons are critical for this control and that their disregulation is involved in narcolepsy, Parkinson's disease, supranuclear palsy and depression. The long-term goal of this project is to understand the synaptic and non-synaptic mechanisms regulating activity of mesopontine cholinergic neurons. Recent compelling evidence indicates that disruption of the novel Hypocretin/Orexin (Hcrt/Orx) peptide system results in narcolepsy - a sleep disorder characterized by excessive daytime sleepiness, sleep fragmentation and the intrusion of rapid eye movement sleep behaviors into wakefulness. Anatomical evidence and our data indicate that mesopontine cholinergic neurons are important targets of these peptides. This proposal focuses on identifying the mechanisms by which Hcrt/Orx acts upon mesopontine cholinergic neurons and associated sleep-related neurons. We will investigate the general hypothesis that Hcrt/Orx peptides regulate both the short-term and long-term excitability of sleeprelated neurons. To do so we will use whole-cell recording and calcium imaging methods in brain slices obtained from control mice and mice lacking the two known orexin receptors. We will address this hypothesis by 1) characterizing the ionic currents responsible for the post-synaptic excitatory actions of Hcrt/Orx peptides; 2) Identifying the sources and consequences of intracellular [Ca2+] changes produced by Hcrt/Orx peptides; 3) Identifying the specific roles of each orexin receptor by utilizing single and double receptor knockout mice and 4) Investigating possible alterations in neuron excitability in the mouse double orexin receptor knockout model of narcolepsy. Collectively, these results will advance the understanding of the molecular and cellular mechanisms underlying sleep regulation and its pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION
TUBEROMAMMILLARY
NUCLEUS
AND
SLEEP/WAKE
Principal Investigator & Institution: Chou, Thomas C.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215
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Timing: Fiscal Year 2001; Project Start 01-MAY-2001 Summary: (applicant's abstract): A long history of studies have suggested that the rostral hypothalamus promotes sleep, while the caudal hypothalamus promotes waking. My research advisor recently identified neurons in the ventrolateral preoptic area (VLPO) that may subserve the rostral hypothalamic sleep-promoting role. These neurons send inhibitory projections to a caudal hypothalamic structure, the tuberomammillary nucleus (TMN). The role of the TMN is unclear, but we propose that it promotes waking, and that it in turn sends inhibitory projections to the VLPO, thus defining a circuit with mutual antagonism between sleep and wake-promoting structures. This model suggests that the sleep-wake state is defined by a pair of competing neural systems, and has implications for disorders of sleep-wake regulation such as narcolepsy. 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 “narcolepsy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for narcolepsy in the PubMed Central database: •
ApoE polymorphisms in narcolepsy. by Gencik M, Dahmen N, Wieczorek S, Kasten M, Gencikova A, Epplen JT.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55694
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Genetic Linkage of Autosomal Recessive Canine Narcolepsy with a [mu] Immunoglobulin Heavy-Chain Switch-Like Segment. by Mignot E, Wang C, Rattazzi C, Gaiser C, Lovett M, Guilleminault C, Dement WC, Grumet FC.; 1991 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51470
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 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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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 narcolepsy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “narcolepsy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for narcolepsy (hyperlinks lead to article summaries): •
A brief history of hypocretin/orexin and narcolepsy. Author(s): Siegel JM, Moore R, Thannickal T, Nienhuis R. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 November; 25(5 Suppl): S14-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682268&dopt=Abstract
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A clinical picture of child and adolescent narcolepsy. Author(s): Dahl RE, Holttum J, Trubnick L. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1994 July-August; 33(6): 834-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8083140&dopt=Abstract
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A comparison of three different sleep schedules for reducing daytime sleepiness in narcolepsy. Author(s): Rogers AE, Aldrich MS, Lin X. Source: Sleep. 2001 June 15; 24(4): 385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403522&dopt=Abstract
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A deletion in the second exon of an HLA-DRB1 allele found in a DR2-negative narcolepsy patient. Author(s): Roushdy J, Santoso S, Kalb R, Meier-Ewert K, Albert ED, Mueller-Eckhardt G. Source: Human Immunology. 1993 May; 37(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7980729&dopt=Abstract
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A hundred years of narcolepsy research. Author(s): Mignot E. Source: Arch Ital Biol. 2001 April; 139(3): 207-20. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11330202&dopt=Abstract
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A model for narcolepsy. Author(s): Mamelak M. Source: Can J Psychol. 1991 June; 45(2): 194-220. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1651801&dopt=Abstract
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A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Author(s): Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. Source: Nature Medicine. 2000 September; 6(9): 991-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973318&dopt=Abstract
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A novel HLA DR17,DQ1 (DQA1-0102/DQB1-0602 positive) haplotype predisposing to narcolepsy in Caucasians. Author(s): Mignot E, Lin X, Hesla PE, Dement WC, Guilleminault C, Grumet FC. Source: Sleep. 1993 December; 16(8): 764-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8165393&dopt=Abstract
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A patient with coexisting narcolepsy and morbid jealousy showing favourable response to fluoxetine. Author(s): Wing YK, Lee S, Chiu HF, Ho CK, Chen CN. Source: Postgraduate Medical Journal. 1994 January; 70(819): 34-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8140016&dopt=Abstract
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A perspective on narcolepsy. Author(s): Mamelak M. Source: L'encephale. 1992 July-August; 18(4): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1338429&dopt=Abstract
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A prepro-orexin gene polymorphism is associated with narcolepsy. Author(s): Gencik M, Dahmen N, Wieczorek S, Kasten M, Bierbrauer J, Anghelescu I, Szegedi A, Menezes Saecker AM, Epplen JT. Source: Neurology. 2001 January 9; 56(1): 115-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148249&dopt=Abstract
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A search for a mutation in the tumour necrosis factor-alpha gene in narcolepsy. Author(s): Kato T, Honda M, Kuwata S, Juji T, Fukuda M, Honda Y, Kato N. Source: Psychiatry and Clinical Neurosciences. 1999 June; 53(3): 421-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10459746&dopt=Abstract
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A validity study of Ullanlinna Narcolepsy Scale in Hong Kong Chinese. Author(s): Wing YK, Li RH, Ho CK, Fong SY, Chow LY, Leung T. Source: Journal of Psychosomatic Research. 2000 November; 49(5): 355-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164060&dopt=Abstract
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Absence of pontine lesions in narcolepsy. Author(s): Frey JL, Heiserman JE. Source: Neurology. 1997 April; 48(4): 1097-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9109908&dopt=Abstract
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Age at onset of narcolepsy in two large populations of patients in France and Quebec. Author(s): Dauvilliers Y, Montplaisir J, Molinari N, Carlander B, Ondze B, Besset A, Billiard M. Source: Neurology. 2001 December 11; 57(11): 2029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739821&dopt=Abstract
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Amphetamines and narcolepsy: use of the Stanford database. Author(s): Guilleminault C. Source: Sleep. 1993 April; 16(3): 199-201. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8506450&dopt=Abstract
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Analysis of the monoamine oxidase genes and the Norrie disease gene locus in narcolepsy. Author(s): Koch H, Craig I, Dahlitz M, Denney R, Parkes D. Source: Lancet. 1999 February 20; 353(9153): 645-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030338&dopt=Abstract
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Anesthesia considerations for patients with narcolepsy. Author(s): Joyce JA. Source: Aana Journal. 1999 February; 67(1): 59-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10488278&dopt=Abstract
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Attention deficits in patients with narcolepsy. Author(s): Rieger M, Mayer G, Gauggel S. Source: Sleep. 2003 February 1; 26(1): 36-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627730&dopt=Abstract
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Attentive and preattentive processing in narcolepsy as revealed by event-related potentials (ERPs). Author(s): Naumann A, Bierbrauer J, Przuntek H, Daum I. Source: Neuroreport. 2001 September 17; 12(13): 2807-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588581&dopt=Abstract
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Autoimmune hypothesis in narcolepsy. Author(s): Carlander B, Eliaou JF, Billiard M. Source: Neurophysiologie Clinique = Clinical Neurophysiology. 1993 January; 23(1): 1522. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8446070&dopt=Abstract
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Autonomic function in narcolepsy: power spectrum analysis of heart rate variability. Author(s): Ferini-Strambi L, Spera A, Oldani A, Zucconi M, Bianchi A, Cerutti S, Smirne S. Source: Journal of Neurology. 1997 April; 244(4): 252-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9112594&dopt=Abstract
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Benefits and risks of pharmacotherapy for narcolepsy. Author(s): Mitler MM, Hayduk R. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(11): 791-809. Review. Erratum In: Drug Saf. 2003(26(3): 186. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222990&dopt=Abstract
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Brain neurotransmitter changes in human narcolepsy. Author(s): Kish SJ, Mamelak M, Slimovitch C, Dixon LM, Lewis A, Shannak K, DiStefano L, Chang LJ, Hornykiewicz O. Source: Neurology. 1992 January; 42(1): 229-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1370862&dopt=Abstract
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Childhood narcolepsy in North China. Author(s): Han F, Chen E, Wei H, Dong X, He Q, Ding D, Strohl KP. Source: Sleep. 2001 May 1; 24(3): 321-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322715&dopt=Abstract
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Childhood narcolepsy. Author(s): Wise MS. Source: Neurology. 1998 February; 50(2 Suppl 1): S37-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484422&dopt=Abstract
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Childhood onset narcolepsy--a case report. Author(s): McKenna L, McNicholas F. Source: European Child & Adolescent Psychiatry. 2003 January; 12(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601564&dopt=Abstract
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Childhood onset of narcolepsy-cataplexy syndrome in Turkey: clinical and genetic study. Author(s): Pelin Z, Bozluolcay M, Kaynak D, Kaynak H. Source: Turk J Pediatr. 2002 October-December; 44(4): 321-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458808&dopt=Abstract
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Chronobiological aspects of narcolepsy. Author(s): Broughton R, Mullington J. Source: Sleep. 1994 December; 17(8 Suppl): S35-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701198&dopt=Abstract
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Circadian distribution of motor activity and immobility in narcolepsy: assessment with continuous motor activity monitoring. Author(s): Middelkoop HA, Lammers GJ, Van Hilten BJ, Ruwhof C, Pijl H, Kamphuisen HA. Source: Psychophysiology. 1995 May; 32(3): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7784537&dopt=Abstract
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Circadian rhythms in narcolepsy: studies on a 90 minute day. Author(s): Dantz B, Edgar DM, Dement WC. Source: Electroencephalography and Clinical Neurophysiology. 1994 January; 90(1): 2435. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7509271&dopt=Abstract
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Clinical aspects of narcolepsy-cataplexy across ethnic groups. Author(s): Okun ML, Lin L, Pelin Z, Hong S, Mignot E. Source: Sleep. 2002 February 1; 25(1): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833858&dopt=Abstract
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Clinical screening for narcolepsy/cataplexy in patients with fibromyalgia. Author(s): Disdier P, Genton P, Bolla G, Verrot D, Christides C, Harle JR, Weiller PJ. Source: Clinical Rheumatology. 1994 March; 13(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8187437&dopt=Abstract
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Clinical significance of cataplexy and HLADR1501 in narcolepsy. Author(s): Inoue Y, Honda Y, Takahashi Y, Nanba K, Ishii A, Saitou K. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047595&dopt=Abstract
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Clinical significance of sleep-related breathing disorder in narcolepsy. Author(s): Inoue Y, Nanba K, Higami S, Honda Y, Takahashi Y, Arai H. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047590&dopt=Abstract
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Clinico-polysomnographic diagnostics of narcolepsy-cataplexy. Author(s): Zachariev Z, Djurkova A. Source: Folia Med (Plovdiv). 1999; 41(2): 5-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534906&dopt=Abstract
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Comparison in symptoms between aged and younger patients with narcolepsy. Author(s): Furuta H, Thorpy MJ, Temple HM. Source: Psychiatry and Clinical Neurosciences. 2001 June; 55(3): 241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422857&dopt=Abstract
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Complete remission of narcolepsy after surgical treatment of an arachnoid cyst in the cerebellopontine angle. Author(s): Nakano H, Ogashiwa M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1995 February; 58(2): 264. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7876881&dopt=Abstract
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Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Author(s): Mignot E, Lin L, Rogers W, Honda Y, Qiu X, Lin X, Okun M, Hohjoh H, Miki T, Hsu S, Leffell M, Grumet F, Fernandez-Vina M, Honda M, Risch N. Source: American Journal of Human Genetics. 2001 March; 68(3): 686-99. Epub 2001 February 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179016&dopt=Abstract
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Consideration of narcolepsy in the differential diagnosis of chronic fatigue syndrome. Author(s): Ambrogetti A, Olson LG. Source: The Medical Journal of Australia. 1994 April 4; 160(7): 426-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8007866&dopt=Abstract
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Continuing education program: integrating an understanding of sleep knowledge into your practice. Part 2. Screening for sleep-related disorders: sleep apnea and narcolepsy (continuing education credit). Author(s): Shaver JL, Rodgers AE. Source: The American Nurse. 1994 November-December; 26(10): 24-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7810927&dopt=Abstract
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Controversies in the diagnosis of narcolepsy. Author(s): Guilleminault C, Mignot E, Partinen M. Source: Sleep. 1994 December; 17(8 Suppl): S1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701189&dopt=Abstract
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CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Author(s): Ripley B, Overeem S, Fujiki N, Nevsimalova S, Uchino M, Yesavage J, Di Monte D, Dohi K, Melberg A, Lammers GJ, Nishida Y, Roelandse FW, Hungs M, Mignot E, Nishino S. Source: Neurology. 2001 December 26; 57(12): 2253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756606&dopt=Abstract
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CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia. Author(s): Kanbayashi T, Inoue Y, Chiba S, Aizawa R, Saito Y, Tsukamoto H, Fujii Y, Nishino S, Shimizu T. Source: Journal of Sleep Research. 2002 March; 11(1): 91-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869432&dopt=Abstract
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Daytime sleep inertia in narcolepsy-cataplexy. Author(s): Mullington J, Broughton R. Source: Sleep. 1994 February; 17(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8191205&dopt=Abstract
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Delta sleep-inducing peptide in normal humans and in patients with sleep apnea and narcolepsy. Author(s): Vgontzas AN, Friedman TC, Chrousos GP, Bixler EO, Vela-Bueno A, Kales A. Source: Peptides. 1995; 16(6): 1153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8532601&dopt=Abstract
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Determination of sleep latency in polysomnographic evaluations of daytime somnolence in patients with sleep apnea and patients with narcolepsy. Author(s): Browman CP, Winslow DH. Source: Clin Electroencephalogr. 1989 January; 20(1): 45-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2924426&dopt=Abstract
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Diagnoses of narcolepsy and sleep apnea syndrome. Author(s): Zahariev Z. Source: Folia Med (Plovdiv). 1995; 37(4A Suppl): 85. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8655083&dopt=Abstract
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Diagnoses received by narcolepsy patients in the year prior to diagnosis by a sleep specialist. Author(s): Kryger MH, Walid R, Manfreda J. Source: Sleep. 2002 February 1; 25(1): 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833859&dopt=Abstract
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Diagnosing narcolepsy through the simultaneous clinical and electrophysiologic analysis of cataplexy. Author(s): Dyken ME, Yamada T, Lin-Dyken DC, Seaba P, Yeh M. Source: Archives of Neurology. 1996 May; 53(5): 456-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624222&dopt=Abstract
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Diagnostic aspects of narcolepsy. Author(s): Aldrich MS. Source: Neurology. 1998 February; 50(2 Suppl 1): S2-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484416&dopt=Abstract
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Diagnostic criteria for narcolepsy and HLA-DR2 frequencies. Author(s): Matsuki K, Honda Y, Juji T. Source: Tissue Antigens. 1987 October; 30(4): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3120349&dopt=Abstract
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Differences between REM and NREM sleepiness measured by event-related potentials (P300, CNV), MSLT and subjective estimate in narcolepsy-cataplexy. Author(s): Broughton RJ, Aguirre M. Source: Electroencephalography and Clinical Neurophysiology. 1987 October; 67(4): 317-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2441964&dopt=Abstract
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Differences in electroencephalogram power densities between genuine narcolepsy and secondary narcolepsy. Author(s): Honma H, Kohsaka M, Fukuda N, Kobayashi R, Sakakibara S, Koyama T. Source: Psychiatry and Clinical Neurosciences. 2000 June; 54(3): 326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11186097&dopt=Abstract
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Disorders of excessive sleepiness: narcolepsy and hypersomnia. Author(s): Manfredi RL, Brennan RW, Cadieux RJ. Source: Seminars in Neurology. 1987 September; 7(3): 250-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3332460&dopt=Abstract
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Dopamine D2 receptors quantified in vivo in human narcolepsy. Author(s): MacFarlane JG, List SJ, Moldofsky H, Firnau G, Chen JJ, Szechtman H, Garnett S, Nahmias C. Source: Biological Psychiatry. 1997 February 1; 41(3): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9024953&dopt=Abstract
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Dopamine D2-receptors in human narcolepsy: a SPECT study with 123I-IBZM. Author(s): Hublin C, Launes J, Nikkinen P, Partinen M. Source: Acta Neurologica Scandinavica. 1994 September; 90(3): 186-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7847059&dopt=Abstract
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DQ (rather than DR) gene marks susceptibility to narcolepsy. Author(s): Matsuki K, Grumet FC, Lin X, Gelb M, Guilleminault C, Dement WC, Mignot E. Source: Lancet. 1992 April 25; 339(8800): 1052. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1349071&dopt=Abstract
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DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans. Author(s): Mignot E, Lin X, Arrigoni J, Macaubas C, Olive F, Hallmayer J, Underhill P, Guilleminault C, Dement WC, Grumet FC. Source: Sleep. 1994 December; 17(8 Suppl): S60-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701202&dopt=Abstract
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DR/DQ typing and narcolepsy. Author(s): Hollingsworth PM, Peter JB. Source: Lancet. 1990 April 14; 335(8694): 913. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1969999&dopt=Abstract
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DR2-negative narcolepsy. Author(s): Andreas-Zietz A, Keller E, Scholz S, Albert ED, Roth B, Nevsimalova S, Sonka K, Docekal P, Ivaskova E, Schulz H, et al. Source: Lancet. 1986 September 20; 2(8508): 684-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2876150&dopt=Abstract
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DR2-positive monozygotic twins discordant for narcolepsy. Author(s): Pollmacher T, Schulz H, Geisler P, Kiss E, Albert ED, Schwarzfischer F. Source: Sleep. 1990 August; 13(4): 336-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2267476&dopt=Abstract
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Dream mentation production and narcolepsy: a critique. Author(s): Nielsen T. Source: Consciousness and Cognition. 2000 December; 9(4): 510-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150219&dopt=Abstract
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Dream-disturbed sleep in insomnia and narcolepsy. Author(s): Lee JH, Bliwise DL, Lebret-Bories E, Guilleminault C, Dement WC. Source: The Journal of Nervous and Mental Disease. 1993 May; 181(5): 320-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8501449&dopt=Abstract
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Effect of L-dopa on periodic movements in sleep in narcolepsy. Author(s): Bedard MA, Montplaisir J, Godbout R. Source: European Neurology. 1987; 27(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2957203&dopt=Abstract
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Effective treatment of narcolepsy with codeine in a patient receiving hemodialysis. Author(s): Benbadis SR. Source: Pharmacotherapy. 1996 May-June; 16(3): 463-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8726607&dopt=Abstract
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Effectiveness of yohimbine in treating narcolepsy. Author(s): Wooten V. Source: Southern Medical Journal. 1994 November; 87(11): 1065-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7973885&dopt=Abstract
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Effects of bromocriptine in human narcolepsy. Author(s): Boivin DB, Montplaisir J, Lambert C. Source: Clinical Neuropharmacology. 1993 April; 16(2): 120-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8477408&dopt=Abstract
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Effects of bromocriptine on periodic limb movements in human narcolepsy. Author(s): Boivin DB, Lorrain D, Montplaisir J. Source: Neurology. 1993 October; 43(10): 2134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8413980&dopt=Abstract
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Effects of clonidine in narcolepsy. Author(s): Salin-Pascual R, de la Fuente JR, Fernandez-Guardiola A. Source: The Journal of Clinical Psychiatry. 1985 December; 46(12): 528-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4066618&dopt=Abstract
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Effects of DSIP on narcolepsy. Author(s): Schneider-Helmert D. Source: European Neurology. 1984; 23(5): 353-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6548968&dopt=Abstract
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Effects of modafinil on symptomatology of human narcolepsy. Author(s): Boivin DB, Montplaisir J, Petit D, Lambert C, Lubin S. Source: Clinical Neuropharmacology. 1993 February; 16(1): 46-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8093681&dopt=Abstract
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Effects of protriptyline on vigilance and information processing in narcolepsy. Author(s): Henry GK, Hart RP, Kwentus JA, Sicola MJ. Source: Psychopharmacology. 1988; 95(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3133688&dopt=Abstract
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Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures. Author(s): Scrima L, Hartman PG, Johnson FH Jr, Hiller FC. Source: Biological Psychiatry. 1989 August; 26(4): 331-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2669980&dopt=Abstract
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Efficacy of trazodone in narcolepsy. Author(s): Sandyk R. Source: European Neurology. 1985; 24(5): 335-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4054183&dopt=Abstract
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Electromagnetic field of mobile phones affects visual event related potential in patients with narcolepsy. Author(s): Jech R, Sonka K, Ruzicka E, Nebuzelsky A, Bohm J, Juklickova M, Nevsimalova S. Source: Bioelectromagnetics. 2001 October; 22(7): 519-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568938&dopt=Abstract
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Electrophysiological brain stem investigations in idiopathic narcolepsy. Author(s): Marx JJ, Urban PP, Hopf HC, Grun B, Querings K, Dahmen N. Source: Journal of Neurology. 1998 August; 245(8): 537-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747918&dopt=Abstract
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Emotional experience during rapid-eye-movement sleep in narcolepsy. Author(s): Fosse R, Stickgold R, Hobson JA. Source: Sleep. 2002 November 1; 25(7): 724-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405607&dopt=Abstract
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Epidemiology of narcolepsy. Author(s): Hublin C, Partinen M, Kaprio J, Koskenvuo M, Guilleminault C. Source: Sleep. 1994 December; 17(8 Suppl): S7-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701204&dopt=Abstract
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Episodic cluster headache and narcolepsy: a case report. Author(s): Alberca R, Botebol G, Boza F, Navarro A. Source: Cephalalgia : an International Journal of Headache. 1991 July; 11(3): 113-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1889066&dopt=Abstract
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Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy. Author(s): Jasinski DR, Kovacevic-Ristanovic R. Source: Clinical Neuropharmacology. 2000 May-June; 23(3): 149-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895398&dopt=Abstract
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Evaluation of treatment with stimulants in narcolepsy. Author(s): Mitler MM. Source: Sleep. 1994 December; 17(8 Suppl): S103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701190&dopt=Abstract
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Evidence of a perceptual-encoding deficit in narcolepsy? Author(s): Henry GK, Satz P, Heilbronner RL. Source: Sleep. 1993 February; 16(2): 123-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8446831&dopt=Abstract
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Excessive daytime sleepiness and the pathophysiology of narcolepsy-cataplexy: a laboratory perspective. Author(s): Broughton R, Valley V, Aguirre M, Roberts J, Suwalski W, Dunham W. Source: Sleep. 1986; 9(1 Pt 2): 205-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3704444&dopt=Abstract
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Familial aspects of narcolepsy-cataplexy in the Czech Republic. Author(s): Nevsimalova S, Mignot E, Sonka K, Arrigoni JL. Source: Sleep. 1997 November; 20(11): 1021-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9456468&dopt=Abstract
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Familial multiple sclerosis associated with narcolepsy. Author(s): Ekbom K. Source: Archives of Neurology. 1966 October; 15(4): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5912493&dopt=Abstract
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Familial narcolepsy in Finland. Author(s): Hublin C, Partinen M, Koskimies S. Source: Acta Neurologica Scandinavica. 1991 June; 83(6): 388-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1887761&dopt=Abstract
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Familial patterns of narcolepsy. Author(s): Guilleminault C, Mignot E, Grumet FC. Source: Lancet. 1989 December 9; 2(8676): 1376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2574313&dopt=Abstract
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Family studies in narcolepsy. Author(s): Billiard M, Pasquie-Magnetto V, Heckman M, Carlander B, Besset A, Zachariev Z, Eliaou JF, Malafosse A. Source: Sleep. 1994 December; 17(8 Suppl): S54-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701201&dopt=Abstract
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Fibrositis syndrome and narcolepsy. Author(s): Disdier P, Genton P, Milandre C, Bernard PM, Millet Y. Source: The Journal of Rheumatology. 1993 May; 20(5): 888-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8101569&dopt=Abstract
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Florid refractory schizophrenias that turn out to be treatable variants of HLAassociated narcolepsy. Author(s): Douglass AB, Hays P, Pazderka F, Russell JM. Source: The Journal of Nervous and Mental Disease. 1991 January; 179(1): 12-7; Discussion 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1985143&dopt=Abstract
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Forty-eight-hour polysomnographic evaluation of narcolepsy. Author(s): Browman CP, Gujavarty KS, Yolles SF, Mitler MM. Source: Sleep. 1986; 9(1 Pt 2): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3704440&dopt=Abstract
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Fragmented sleep, daytime somnolence and age in narcolepsy. Author(s): Lamphere J, Young D, Roehrs T, Wittig RM, Zorick F, Roth T. Source: Clin Electroencephalogr. 1989 January; 20(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2924427&dopt=Abstract
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Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. Author(s): Lammers GJ, Arends J, Declerck AC, Ferrari MD, Schouwink G, Troost J. Source: Sleep. 1993 April; 16(3): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8506453&dopt=Abstract
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Gammahydroxybutyrate in narcolepsy. Author(s): Kalra MA, Hart LL. Source: The Annals of Pharmacotherapy. 1992 May; 26(5): 647-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1591425&dopt=Abstract
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gamma-Hydroxybutyrate in narcolepsy. Author(s): Price PA, Schachter M, Smith SJ, Baxter RC, Parkes JD. Source: Annals of Neurology. 1981 February; 9(2): 198. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7235637&dopt=Abstract
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Gelineau's narcolepsy relieved by opiates. Author(s): Harper JM. Source: Lancet. 1981 January 10; 1(8211): 92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6109135&dopt=Abstract
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Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Author(s): Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, Sakurai T. Source: Neuron. 2001 May; 30(2): 345-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394998&dopt=Abstract
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Genetic and familial aspects of narcolepsy. Author(s): Mignot E. Source: Neurology. 1998 February; 50(2 Suppl 1): S16-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484418&dopt=Abstract
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Genetic factors in canine narcolepsy. Author(s): Foutz AS, Mitler MM, Cavalli-Sforza LL, Dement WC. Source: Sleep. 1979 Summer; 1(4): 413-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=574310&dopt=Abstract
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Genetic heterogeneity in narcolepsy. Author(s): Singh SM, George CF, Kryger MH, Jung JH. Source: Lancet. 1990 March 24; 335(8691): 726-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1969083&dopt=Abstract
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Genetic markers in familial narcolepsy. Author(s): Orr WC, Othman JA, Rundell OH. Source: Sleep. 1991 June; 14(3): 270-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1896730&dopt=Abstract
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Genetic markers in narcolepsy. Author(s): Langdon N, Welsh KI, van Dam M, Vaughan RW, Parkes D. Source: Lancet. 1984 November 24; 2(8413): 1178-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6150235&dopt=Abstract
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Genetic studies in narcolepsy, a disorder affecting REM sleep. Author(s): Faraco J, Lin X, Li R, Hinton L, Lin L, Mignot E. Source: The Journal of Heredity. 1999 January-February; 90(1): 129-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9987919&dopt=Abstract
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Genetic studies in the sleep disorder narcolepsy. Author(s): Kadotani H, Faraco J, Mignot E. Source: Genome Research. 1998 May; 8(5): 427-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9582188&dopt=Abstract
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Genetics of narcolepsy and other sleep disorders. Author(s): Mignot E. Source: American Journal of Human Genetics. 1997 June; 60(6): 1289-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9199548&dopt=Abstract
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Good sleep, bad sleep: a meta-analysis of polysomnographic measures in insomnia, depression, and narcolepsy. Author(s): Hudson JI, Pope HG, Sullivan LE, Waternaux CM, Keck PE, Broughton RJ. Source: Biological Psychiatry. 1992 December 1; 32(11): 958-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1467388&dopt=Abstract
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Haplotype analyses with the human leucocyte antigen and tumour necrosis factoralpha genes in narcolepsy families. Author(s): Hohjoh H, Terada N, Miki T, Honda Y, Tokunaga K. Source: Psychiatry and Clinical Neurosciences. 2001 February; 55(1): 37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235856&dopt=Abstract
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Health-related quality of life effects of modafinil for treatment of narcolepsy. Author(s): Beusterien KM, Rogers AE, Walsleben JA, Emsellem HA, Reblando JA, Wang L, Goswami M, Steinwald B. Source: Sleep. 1999 September 15; 22(6): 757-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10505821&dopt=Abstract
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Health-related quality of life in narcolepsy. Author(s): Daniels E, King MA, Smith IE, Shneerson JM. Source: Journal of Sleep Research. 2001 March; 10(1): 75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285058&dopt=Abstract
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Heterozygosity at the canarc-1 locus can confer susceptibility for narcolepsy: induction of cataplexy in heterozygous asymptomatic dogs after administration of a combination of drugs acting on monoaminergic and cholinergic systems. Author(s): Mignot E, Nishino S, Sharp LH, Arrigoni J, Siegel JM, Reid MS, Edgar DM, Ciaranello RD, Dement WC. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 1993 March; 13(3): 1057-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8095066&dopt=Abstract
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HLA and hypocretin studies in Korean patients with narcolepsy. Author(s): Hong SC, Leen-Kim, Park SA, Han JH, Lee SP, Lin L, Okun M, Nishino S, Mignot E. Source: Sleep. 2002 June 15; 25(4): 440-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071546&dopt=Abstract
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HLA and narcolepsy. Author(s): Hollingsworth PN, Dawkins RL, Peter JB. Source: Neurology. 1993 July; 43(7): 1444-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8327158&dopt=Abstract
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HLA class II haplotype and sequence analysis support a role for DQ in narcolepsy. Author(s): Ellis MC, Hetisimer AH, Ruddy DA, Hansen SL, Kronmal GS, McClelland E, Quintana L, Drayna DT, Aldrich MS, Mignot E. Source: Immunogenetics. 1997; 46(5): 410-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9271631&dopt=Abstract
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HLA DR2 in narcolepsy with sleep-onset REM periods but not cataplexy. Author(s): Rosenthal L, Roehrs TA, Hayashi H, Zorick FJ, Wittig RM, Rosenthal J, Roth T. Source: Biological Psychiatry. 1991 October 15; 30(8): 830-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1751625&dopt=Abstract
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HLA haplotypes, polysomnography, and pedigrees in a case series of patients with narcolepsy. Author(s): Hayduk R, Flodman P, Spence MA, Erman MK, Mitler MM. Source: Sleep. 1997 October; 20(10): 850-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415944&dopt=Abstract
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HLA-DQA, -DQB and -DRB allele contribution to narcolepsy susceptibility. Author(s): Planelles D, Puig N, Beneto A, Gomez E, Rubio P, Mirabet V, Bonanad S, Blasco I, Montoro JA. Source: European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics. 1997 December; 24(6): 409-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9534039&dopt=Abstract
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HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. US Modafinil in Narcolepsy Multicenter Study Group. Author(s): Pelin Z, Guilleminault C, Risch N, Grumet FC, Mignot E. Source: Tissue Antigens. 1998 January; 51(1): 96-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459509&dopt=Abstract
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HLA-DR2 negative narcolepsy in Australian Caucasians: clinical features, serology and sequence specific oligonucleotide typing. Author(s): Reutens DC, Haddad AP, Cantwell L, Berkovic SF. Source: Journal of the Neurological Sciences. 1992 November; 113(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1469452&dopt=Abstract
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HLA-D-region genomic DNA restriction fragments in DRw15 (DR2) familial narcolepsy. Author(s): Ditta SD, George CF, Singh SM. Source: Sleep. 1992 February; 15(1): 48-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1348374&dopt=Abstract
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Homeostasis and narcolepsy. Author(s): Besset A, Tafti M, Nobile L, Billiard M. Source: Sleep. 1994 December; 17(8 Suppl): S29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701197&dopt=Abstract
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Hypersomnolence and narcolepsy; a pragmatic diagnostic neurophysiological approach. Author(s): Boon P, Pevernagie D, Schrans D. Source: Acta Neurol Belg. 2002 March; 102(1): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094557&dopt=Abstract
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Hypocretin (orexin) deficiency in human narcolepsy. Author(s): Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Source: Lancet. 2000 January 1; 355(9197): 39-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10615891&dopt=Abstract
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Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status. Author(s): Krahn LE, Pankratz VS, Oliver L, Boeve BF, Silber MH. Source: Sleep. 2002 November 1; 25(7): 733-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405608&dopt=Abstract
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Hypocretin deficiency in familial symptomatic narcolepsy. Author(s): Melberg A, Ripley B, Lin L, Hetta J, Mignot E, Nishino S. Source: Annals of Neurology. 2001 January; 49(1): 136-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198287&dopt=Abstract
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Hypocretin/orexin and sleep: implications for the pathophysiology and diagnosis of narcolepsy. Author(s): Overeem S, Scammell TE, Lammers GJ. Source: Current Opinion in Neurology. 2002 December; 15(6): 739-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447114&dopt=Abstract
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Hypocretin/orexin, sleep and narcolepsy. Author(s): Hungs M, Mignot E. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2001 May; 23(5): 397-408. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340621&dopt=Abstract
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ICSD diagnostic criteria for narcolepsy: interobserver reliability. Intemational Classification of Sleep Disorders. Author(s): Vignatelli L, Plazzi G, Bassein L, Barbato A, De Vincentiis A, Lugaresi E, D'Alessandro R; GIN-SEN. Gruppo Italiano Narcolessia-Studio Epidemiologico Nazionale. Source: Sleep. 2002 March 15; 25(2): 193-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902428&dopt=Abstract
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Identification of a telomeric boundary of the HLA region with potential for predisposition to human narcolepsy. Author(s): Miyagawa T, Hohjoh H, Honda Y, Juji T, Tokunaga K. Source: Immunogenetics. 2000 November; 52(1-2): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11132147&dopt=Abstract
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Idiopathic narcolepsy: effect of naloxone studied in one of three patients with unelevated beta-endorphin-like immunoreactivity plasma levels. Author(s): Pasi A, Wettstein A, Foletta D, Gramsch C. Source: Journal of Clinical Psychopharmacology. 1982 June; 2(3): 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6284804&dopt=Abstract
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IgH (mu-switch and gamma-1) region restriction fragment length polymorphism in human narcolepsy. Author(s): Singh SM, George CF, Ott RN, Rattazzi C, Guilleminault C, Dement WC, Mignot E. Source: Journal of Clinical Immunology. 1996 July; 16(4): 208-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8840222&dopt=Abstract
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Immune factors in narcolepsy. Author(s): Langdon N, Lock C, Welsh K, Vergani D, Dorow R, Wachtel H, Palenschat D, Parkes JD. Source: Sleep. 1986; 9(1 Pt 2): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3486441&dopt=Abstract
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Impact of drug regulations and diversion control systems on legitimate narcolepsy patients. Author(s): Piscopo JA. Source: Nida Res Monogr. 1993; 131: 249-59. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8105384&dopt=Abstract
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Impaired circadian waking arousal in narcolepsy-cataplexy. Author(s): Broughton R, Krupa S, Boucher B, Rivers M, Mullington J. Source: Sleep Res Online. 1998; 1(4): 159-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382873&dopt=Abstract
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Importance of mazindol in the treatment of narcolepsy. Author(s): Vespignani H, Barroche G, Escaillas JP, Weber M. Source: Sleep. 1984; 7(3): 274-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6484432&dopt=Abstract
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In vivo and in vitro immune variables in patients with narcolepsy and HLA-DR2 matched controls. Author(s): Hinze-Selch D, Wetter TC, Zhang Y, Lu HC, Albert ED, Mullington J, Wekerle H, Holsboer F, Pollmacher T. Source: Neurology. 1998 April; 50(4): 1149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566413&dopt=Abstract
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Increased body-mass index in patients with narcolepsy. Author(s): Schuld A, Hebebrand J, Geller F, Pollmacher T. Source: Lancet. 2000 April 8; 355(9211): 1274-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770327&dopt=Abstract
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Increased REM density in narcolepsy-cataplexy and the polysymptomatic form of idiopathic hypersomnia. Author(s): Vankova J, Nevsimalova S, Sonka K, Spackova N, Svejdova-Blazejova K. Source: Sleep. 2001 September 15; 24(6): 707-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560185&dopt=Abstract
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Infancy onset of symptoms of narcolepsy in a child. Author(s): Witmans MB, Kirk VG. Source: Clinical Pediatrics. 2002 October; 41(8): 609-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403379&dopt=Abstract
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Insomnia, narcolepsy, and sleep apneas. Author(s): Guilleminault C, Eldridge F, Dement WC. Source: Bull Physiopathol Respir (Nancy). 1972 September-October; 8(5): 1127-38. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4348638&dopt=Abstract
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Interpersonal problems in narcolepsy. Author(s): Salzman C. Source: Psychosomatics. 1976; 17(1): 49-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=944936&dopt=Abstract
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Introduction to the mechanism of action of different treatments of narcolepsy. Author(s): Parkes D. Source: Sleep. 1994 December; 17(8 Suppl): S93-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701207&dopt=Abstract
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Investigations into the neurologic basis of narcolepsy. Author(s): Guilleminault C, Heinzer R, Mignot E, Black J. Source: Neurology. 1998 February; 50(2 Suppl 1): S8-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484417&dopt=Abstract
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Involvement of hypocretins/orexins in sleep disorders and narcolepsy. Author(s): Brown RE. Source: Drug News Perspect. 2003 March; 16(2): 75-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792667&dopt=Abstract
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Is there an infectious origin of narcolepsy? Author(s): Mueller-Eckhardt G, Meier-Ewart K, Schiefer HG. Source: Lancet. 1990 February 17; 335(8686): 424. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1968163&dopt=Abstract
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Juvenile onset narcolepsy in an individual with Turner syndrome. A case report. Author(s): George CF, Singh SM. Source: Sleep. 1991 June; 14(3): 267-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1896729&dopt=Abstract
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L-dopa and narcolepsy. Author(s): Friedman EH. Source: Neurology. 1992 August; 42(8): 1640-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1641171&dopt=Abstract
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Lesson of the week: Narcolepsy mistaken for epilepsy. Author(s): Zeman A, Douglas N, Aylward R. Source: Bmj (Clinical Research Ed.). 2001 January 27; 322(7280): 216-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159621&dopt=Abstract
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Letter to the editor regarding our previous publication: “Secondary narcolepsy in children with brain tumors,” SLEEP 2002; 25:435-439. Author(s): Marcus CL, Mignot E. Source: Sleep. 2003 March 15; 26(2): 228. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683485&dopt=Abstract
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Letter: Animal model of narcolepsy-cataplexy. Author(s): Mitler MM. Source: J Am Vet Med Assoc. 1975 April 1; 166(7): 643. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1170149&dopt=Abstract
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Letter: Narcolepsy. Author(s): Broughton R. Source: Can Med Assoc J. 1974 May 4; 110(9): 1007. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4362819&dopt=Abstract
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Letter: Narcolepsy. Author(s): Shokeir MH. Source: Can Med Assoc J. 1974 April 6; 110(7): 756. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4825143&dopt=Abstract
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Letter: Narcolepsy: REM sleep suppression by L-dopa. Author(s): Gilbert JC, Willer JC, Bernheim-Chaltelain C, Ecoffet M, Jaillon P. Source: The New England Journal of Medicine. 1976 April 8; 294(15): 849. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=175275&dopt=Abstract
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Levo(-) amphetamine and dextro(+) amphetamine in the treatment of narcolepsy. Author(s): Parkes JD, Fenton GW. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1973 December; 36(6): 1076-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4359162&dopt=Abstract
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Life effects of narcolepsy in 180 patients from North America, Asia and Europe compared to matched controls. Author(s): Broughton R, Ghanem Q, Hishikawa Y, Sugita Y, Nevsimalova S, Roth B. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1981 November; 8(4): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7326610&dopt=Abstract
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Life effects of narcolepsy: relationships to geographic origin (North American, Asian or European) and to other patient and illness variables. Author(s): Broughton R, Ghanem Q, Hishikawa Y, Sugita Y, Nevsimalova S, Roth B. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1983 May; 10(2): 100-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6861006&dopt=Abstract
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Life events in the year preceding the onset of narcolepsy. Author(s): Orellana C, Villemin E, Tafti M, Carlander B, Besset A, Billiard M. Source: Sleep. 1994 December; 17(8 Suppl): S50-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701200&dopt=Abstract
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Linkage of human narcolepsy with HLA association to chromosome 4p13-q21. Author(s): Nakayama J, Miura M, Honda M, Miki T, Honda Y, Arinami T. Source: Genomics. 2000 April 1; 65(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10777671&dopt=Abstract
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Longer auditory and visual P300 latencies in patients with narcolepsy. Author(s): Sangal RB, Sangal JM, Belisle C. Source: Clin Electroencephalogr. 1999 January; 30(1): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891190&dopt=Abstract
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Long-latency auditory evoked responses during sleep deprivation and in narcolepsy. Author(s): Pressman MR, Spielman AJ, Pollak CP, Weitzman ED. Source: Sleep. 1982; 5 Suppl 2: S147-56. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7156649&dopt=Abstract
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Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy. Author(s): Schuld A, Blum WF, Pollmacher T. Source: Annals of Neurology. 2002 May; 51(5): 660; Author Reply 660-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112120&dopt=Abstract
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Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy. Author(s): Nishino S, Ripley B, Overeem S, Nevsimalova S, Lammers GJ, Vankova J, Okun M, Rogers W, Brooks S, Mignot E. Source: Annals of Neurology. 2001 September; 50(3): 381-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558795&dopt=Abstract
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L-tyrosine in the treatment of narcolepsy. Author(s): Roufs JB. Source: Medical Hypotheses. 1990 December; 33(4): 269-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2090930&dopt=Abstract
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Lumbar subarachnoid fallopian shunt in the treatment of pseudotumor cerebri in a patient with narcolepsy. Author(s): Goald HJ, Lloyd RA. Source: Journal of the National Medical Association. 1968 May; 60(3): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5652590&dopt=Abstract
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Major histocompatibility class II molecules in the CNS: increased microglial expression at the onset of narcolepsy in canine model. Author(s): Tafti M, Nishino S, Aldrich MS, Liao W, Dement WC, Mignot E. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 1996 August 1; 16(15): 4588-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8764647&dopt=Abstract
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Management of narcolepsy in pregnancy. Author(s): Hoover-Stevens S, Kovacevic-Ristanovic R. Source: Clinical Neuropharmacology. 2000 July-August; 23(4): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11020119&dopt=Abstract
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MAO-A and COMT polymorphisms and gene effects in narcolepsy. Author(s): Dauvilliers Y, Neidhart E, Lecendreux M, Billiard M, Tafti M. Source: Molecular Psychiatry. 2001 July; 6(4): 367-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443519&dopt=Abstract
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Mazindol in long-term treatment of narcolepsy. Author(s): Alvarez B, Dahlitz M, Grimshaw J, Parkes JD. Source: Lancet. 1991 May 25; 337(8752): 1293-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1674093&dopt=Abstract
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Mazindol in the treatment of narcolepsy. Author(s): Parkes JD, Schachter M. Source: Acta Neurologica Scandinavica. 1979 October; 60(4): 250-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=525256&dopt=Abstract
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Metamemory in narcolepsy. Author(s): Hood B, Bruck D. Source: Journal of Sleep Research. 1997 September; 6(3): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9358399&dopt=Abstract
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Method of promoting blood circulation to eliminate stasis in treatment of narcolepsy. Report of 4 cases. Author(s): Chen JH, Gao Y. Source: J Tradit Chin Med. 1982 March; 2(1): 67-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6765692&dopt=Abstract
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Methysergide in the treatment of narcolepsy. Author(s): Wyler AR, Wilkus RJ, Troupin AS. Source: Archives of Neurology. 1975 April; 32(4): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=164849&dopt=Abstract
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Modafinil approved for narcolepsy. Author(s): Miller JL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 February 15; 56(4): 304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712046&dopt=Abstract
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Modafinil for narcolepsy. Author(s): Teitelman E. Source: The American Journal of Psychiatry. 2001 June; 158(6): 970-1. Corrected and Republished In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384922&dopt=Abstract
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Monoamine interactions in narcolepsy and hypersomnia: a preliminary report. Author(s): Faull KF, Thiemann S, King RJ, Guilleminault C. Source: Sleep. 1986; 9(1 Pt 2): 246-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2422716&dopt=Abstract
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Monozygotic twins incompletely concordant for narcolepsy. Author(s): Honda M, Honda Y, Uchida S, Miyazaki S, Tokunaga K. Source: Biological Psychiatry. 2001 June 1; 49(11): 943-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377412&dopt=Abstract
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Motor dyscontrol in narcolepsy: rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder. Author(s): Schenck CH, Mahowald MW. Source: Annals of Neurology. 1992 July; 32(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1642469&dopt=Abstract
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MRI findings in narcolepsy. Author(s): Bassetti C, Aldrich MS, Quint DJ. Source: Sleep. 1997 August; 20(8): 630-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9351130&dopt=Abstract
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Multiple sclerosis and narcolepsy/cataplexy in a monozygotic twin. Author(s): Schrader H, Gotlibsen OB, Skomedal GN. Source: Neurology. 1980 January; 30(1): 105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7188628&dopt=Abstract
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Multiple sclerosis and narcolepsy: possible similar genetic susceptibility. Author(s): Younger DS, Pedley TA, Thorpy MJ. Source: Neurology. 1991 March; 41(3): 447-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2006018&dopt=Abstract
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Multiple sleep latency tests during the development of narcolepsy. Author(s): Carskadon MA, Harvey K, Dement WC. Source: The Western Journal of Medicine. 1981 November; 135(5): 414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7340136&dopt=Abstract
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Muscarinic cholinergic receptors in human narcolepsy: a PET study. Author(s): Sudo Y, Suhara T, Honda Y, Nakajima T, Okubo Y, Suzuki K, Nakashima Y, Yoshikawa K, Okauchi T, Sasaki Y, Matsushita M. Source: Neurology. 1998 November; 51(5): 1297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818849&dopt=Abstract
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Myths & facts. about narcolepsy. Author(s): Quillen T. Source: Nursing. 1993 July; 23(7): 74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8327219&dopt=Abstract
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Narcolepsy and immunity. Author(s): Mignot E, Tafti M, Dement WC, Grumet FC. Source: Advances in Neuroimmunology. 1995; 5(1): 23-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7795891&dopt=Abstract
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Narcolepsy and its treatment with stimulants. ASDA standards of practice. Author(s): Mitler MM, Aldrich MS, Koob GF, Zarcone VP. Source: Sleep. 1994 June; 17(4): 352-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7973321&dopt=Abstract
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Narcolepsy associated with arteriovenous malformation of the diencephalon. Author(s): Clavelou P, Tournilhac M, Vidal C, Georget AM, Picard L, Merienne L. Source: Sleep. 1995 April; 18(3): 202-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7610317&dopt=Abstract
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Narcolepsy drug could be approved for wider use. Author(s): Ault A. Source: Lancet. 2003 October 4; 362(9390): 1128. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558511&dopt=Abstract
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Narcolepsy in animals and man. Author(s): Mignot EJ, Dement WC. Source: Equine Veterinary Journal. 1993 November; 25(6): 476-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8275992&dopt=Abstract
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Narcolepsy in children. Author(s): Challamel MJ, Mazzola ME, Nevsimalova S, Cannard C, Louis J, Revol M. Source: Sleep. 1994 December; 17(8 Suppl): S17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701194&dopt=Abstract
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Narcolepsy in Hong Kong Chinese--a preliminary experience. Author(s): Wing YK, Chiu HF, Ho CK, Chen CN. Source: Aust N Z J Med. 1994 June; 24(3): 304-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7980215&dopt=Abstract
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Narcolepsy in systemic lupus erythematosus. Author(s): Pablos JL, del Rincon E, Francisco F, Mateo I. Source: The Journal of Rheumatology. 1993 February; 20(2): 375-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8474079&dopt=Abstract
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Narcolepsy presenting as dizziness. Author(s): Yee MS, Blakley BW. Source: The Journal of Otolaryngology. 2003 April; 32(2): 118. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866598&dopt=Abstract
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Narcolepsy. Author(s): Chaudhary BA, Husain I. Source: The Journal of Family Practice. 1993 February; 36(2): 207-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8426141&dopt=Abstract
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Narcolepsy. Author(s): Feldman NT. Source: Southern Medical Journal. 2003 March; 96(3): 277-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659360&dopt=Abstract
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Narcolepsy. Author(s): Rogers AE, Dreher HM. Source: Nurs Clin North Am. 2002 December; 37(4): 675-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587367&dopt=Abstract
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Narcolepsy: differential diagnosis or etiology in some cases of bipolar disorder and schizophrenia? Author(s): Douglass AB. Source: Cns Spectr. 2003 February; 8(2): 120-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612497&dopt=Abstract
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Narcolepsy: unequivocal diagnosis after split-screen, video-polysomnographic analysis of a prolonged cataplectic attack. Author(s): Dyken ME, Yamada T, Lin-Dyken DC, Seaba P. Source: Neurology. 1994 April; 44(4): 760-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8164841&dopt=Abstract
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Narcolepsy-like symptoms in a patient with down syndrome and without obstructive sleep apnea. Author(s): Dominguez-Ortega L, Salin-Pascual RJ, Diaz-Gallego E. Source: Sleep. 2003 May 1; 26(3): 285-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749546&dopt=Abstract
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Neurochemical studies of human narcolepsy: alpha-adrenergic receptor autoradiography of human narcoleptic brain and brainstem. Author(s): Aldrich MS, Prokopowicz G, Ockert K, Hollingsworth Z, Penney JB, Albin RL. Source: Sleep. 1994 October; 17(7): 598-608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7846457&dopt=Abstract
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New-onset narcolepsy and paroxetine. Author(s): Owley T, Flaherty J. Source: Psychosomatics. 1994 November-December; 35(6): 585. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7809362&dopt=Abstract
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Night sleep does not predict day sleep in narcolepsy. Author(s): Broughton R, Dunham W, Weisskopf M, Rivers M. Source: Electroencephalography and Clinical Neurophysiology. 1994 July; 91(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7517846&dopt=Abstract
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Non-pharmacological approaches to the treatment of narcolepsy. Author(s): Garma L, Marchand F. Source: Sleep. 1994 December; 17(8 Suppl): S97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701208&dopt=Abstract
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Novel therapies for narcolepsy. Author(s): Brooks S, Black J. Source: Expert Opinion on Investigational Drugs. 2002 December; 11(12): 1821-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457441&dopt=Abstract
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Objective assessment of narcolepsy. Author(s): Thorpy MJ, Wagner DR, Spielman AJ, Weitzman ED. Source: Archives of Neurology. 1983 February; 40(2): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6824448&dopt=Abstract
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Ocular manifestations of narcolepsy. Author(s): Chee PH. Source: The British Journal of Ophthalmology. 1968 January; 52(1): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5710509&dopt=Abstract
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On a case of narcolepsy with paroxysmal phenomena. A diurnal and nocturnal study. Author(s): Vincent D, Favarel-Garrigues B, Faure J, Julien J. Source: Electroencephalography and Clinical Neurophysiology. 1967 September; 23(3): 284. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4167941&dopt=Abstract
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On the problem of heredity in hypersomnia, narcolepsy and dissociated sleep disturbances. Author(s): Nevsimalova-Bruhova S. Source: Acta Univ Carol [med] (Praha). 1973; 19(1-2): 109-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4374074&dopt=Abstract
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On the treatment of narcolepsy. Author(s): Yoss RE, Daly DD. Source: The Medical Clinics of North America. 1968 July; 52(4): 781-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5268119&dopt=Abstract
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On the treatment of rapid eye movement narcolepsy. Author(s): Guilleminault C, Carskadon M, Dement WC. Source: Archives of Neurology. 1974 January; 30(1): 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4357130&dopt=Abstract
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Ophthalmic manifestations of narcolepsy. Author(s): Norman ME, Dyer JA. Source: American Journal of Ophthalmology. 1987 January 15; 103(1): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3799792&dopt=Abstract
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Paediatric narcolepsy: complexities of diagnosis. Author(s): Hood BM, Harbord MG. Source: Journal of Paediatrics and Child Health. 2002 December; 38(6): 618-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410881&dopt=Abstract
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Paraneoplastic limbic encephalitis and possible narcolepsy in a patient with testicular cancer: case study. Author(s): Landolfi JC, Nadkarni M. Source: Neuro-Oncology. 2003 July; 5(3): 214-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816728&dopt=Abstract
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Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy. Author(s): Thannickal TC, Siegel JM, Nienhuis R, Moore RY. Source: Brain Pathology (Zurich, Switzerland). 2003 July; 13(3): 340-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946023&dopt=Abstract
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Perspectives in narcolepsy research and therapy. Author(s): Mignot E. Source: Current Opinion in Pulmonary Medicine. 1996 November; 2(6): 482-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9363189&dopt=Abstract
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Pharmacological aspects of human and canine narcolepsy. Author(s): Nishino S, Mignot E. Source: Progress in Neurobiology. 1997 May; 52(1): 27-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185233&dopt=Abstract
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Pharmacological treatment of narcolepsy. Author(s): Krieger J. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 362A-363A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1498873&dopt=Abstract
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Plasma orexin-A is lower in patients with narcolepsy. Author(s): Higuchi S, Usui A, Murasaki M, Matsushita S, Nishioka N, Yoshino A, Matsui T, Muraoka H, Ishizuka Y, Kanba S, Sakurai T. Source: Neuroscience Letters. 2002 January 25; 318(2): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796186&dopt=Abstract
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Polymorphisms in hypocretin/orexin pathway genes and narcolepsy. Author(s): Olafsdottir BR, Rye DB, Scammell TE, Matheson JK, Stefansson K, Gulcher JR. Source: Neurology. 2001 November 27; 57(10): 1896-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723285&dopt=Abstract
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Polymorphisms in the vicinity of the hypocretin/orexin are not associated with human narcolepsy. Author(s): Hungs M, Lin L, Okun M, Mignot E. Source: Neurology. 2001 November 27; 57(10): 1893-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723284&dopt=Abstract
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Polymorphisms of the tumor necrosis factor receptors: no association with narcolepsy in German patients. Author(s): Wieczorek S, Dahmen N, Jagiello P, Epplen JT, Gencik M. Source: Journal of Molecular Medicine (Berlin, Germany). 2003 February; 81(2): 87-90. Epub 2003 February 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601524&dopt=Abstract
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Pontine lesions in idiopathic narcolepsy. Author(s): Kwen PL, Pullicino P. Source: Neurology. 1998 February; 50(2): 577-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484414&dopt=Abstract
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Posttraumatic narcolepsy in mild to moderate closed head injury. Author(s): Lankford DA, Wellman JJ, O'Hara C. Source: Sleep. 1994 December; 17(8 Suppl): S25-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701196&dopt=Abstract
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Potential role for the narcolepsy- and multiple sclerosis-associated HLA allele DQB1*0602 in schizophrenia subtypes. Author(s): Grosskopf A, Muller N, Malo A, Wank R. Source: Schizophrenia Research. 1998 March 10; 30(2): 187-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549784&dopt=Abstract
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Practice parameters for the treatment of narcolepsy: an update for 2000. Author(s): Littner M, Johnson SF, McCall WV, Anderson WM, Davila D, Hartse SK, Kushida CA, Wise MS, Hirshkowitz M, Woodson BT; Standards of Practice Committee. Source: Sleep. 2001 June 15; 24(4): 451-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403530&dopt=Abstract
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Presentation of narcolepsy after 40. Author(s): Rye DB, Dihenia B, Weissman JD, Epstein CM, Bliwise DL. Source: Neurology. 1998 February; 50(2): 459-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484372&dopt=Abstract
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Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Author(s): Ohayon MM, Priest RG, Zulley J, Smirne S, Paiva T. Source: Neurology. 2002 June 25; 58(12): 1826-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084885&dopt=Abstract
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Problems associated with switch to modafinil - a novel alerting agent in narcolepsy. Author(s): Guilleminault C, Aftab FA, Karadeniz D, Philip P, Leger D. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2000 July; 7(4): 381-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971596&dopt=Abstract
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Pseudo-narcolepsy: case report. Author(s): Hicks JA, Shapiro CM. Source: Journal of Psychiatry & Neuroscience : Jpn. 1999 September; 24(4): 348-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516803&dopt=Abstract
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Psychosocial impact of narcolepsy. Author(s): Broughton WA, Broughton RJ. Source: Sleep. 1994 December; 17(8 Suppl): S45-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701199&dopt=Abstract
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Pupillometric assessment of excessive daytime sleepiness in narcolepsy-cataplexy. Author(s): Newman J, Broughton R. Source: Sleep. 1991 April; 14(2): 121-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1866526&dopt=Abstract
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Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Author(s): Broughton RJ, Fleming JA, George CF, Hill JD, Kryger MH, Moldofsky H, Montplaisir JY, Morehouse RL, Moscovitch A, Murphy WF. Source: Neurology. 1997 August; 49(2): 444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9270575&dopt=Abstract
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Rapid sleep in successive attacks of narcolepsy and the 90- to 100-minute biorhythm. Author(s): Latash LP, Rait ML. Source: Hum Physiol. 1978 May-June; 4(3): 410-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=572814&dopt=Abstract
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Recognition and management of narcolepsy. Author(s): Stores G. Source: Archives of Disease in Childhood. 1999 December; 81(6): 519-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569973&dopt=Abstract
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Reduced cortical gray matter in narcolepsy: preliminary findings with voxel-based morphometry. Author(s): Kaufmann C, Schuld A, Pollmacher T, Auer DP. Source: Neurology. 2002 June 25; 58(12): 1852-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084891&dopt=Abstract
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Reduced leptin levels in human narcolepsy. Author(s): Schuld A, Blum WF, Uhr M, Haack M, Kraus T, Holsboer F, Pollmacher T. Source: Neuroendocrinology. 2000 October; 72(4): 195-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11070422&dopt=Abstract
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Reduced number of hypocretin neurons in human narcolepsy. Author(s): Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Source: Neuron. 2000 September; 27(3): 469-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055430&dopt=Abstract
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Regulation of cortisol secretion in Parkinson's syndrome and narcolepsy. Author(s): Gallagher BB. Source: The Journal of Clinical Endocrinology and Metabolism. 1971 June; 32(6): 796-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4325218&dopt=Abstract
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Relative efficacy of drugs for the treatment of sleepiness in narcolepsy. Author(s): Mitler MM, Hajdukovic R. Source: Sleep. 1991 June; 14(3): 218-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1680245&dopt=Abstract
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REM changes in narcolepsy with selegiline. Author(s): Reinish LW, MacFarlane JG, Sandor P, Shapiro CM. Source: Sleep. 1995 June; 18(5): 362-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7676170&dopt=Abstract
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REM narcolepsy, clinical polysomnographic and computerized electroencephalographic studies. Author(s): Popoviciu L, Delast-Popoviciu D, Bagathai J. Source: Rom J Neurol Psychiatry. 1992 October-December; 30(4): 301-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1299307&dopt=Abstract
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REM sleep and NREM sleep in narcolepsy and hypersomnia. Author(s): Roth B, Bruhova S, Lehovsky M. Source: Electroencephalography and Clinical Neurophysiology. 1969 February; 26(2): 176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4183371&dopt=Abstract
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REM sleep disinhibition at sleep onset: a comparison between narcolepsy and depression. Author(s): Pollmacher T, Mullington J, Lauer CJ. Source: Biological Psychiatry. 1997 October 15; 42(8): 713-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9325565&dopt=Abstract
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REM sleep episodes during the maintenance of wakefulness test in patients with sleep apnea syndrome and patients with narcolepsy. Author(s): Browman CP, Gujavarty KS, Sampson MG, Mitler MM. Source: Sleep. 1983; 6(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6844794&dopt=Abstract
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Retrognathia and sleep apnea. A life-threatening condition masquerading as narcolepsy. Author(s): Imes NK, Orr WC, Smith RO, Rogers RM. Source: Jama : the Journal of the American Medical Association. 1977 April 11; 237(15): 1596-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=576659&dopt=Abstract
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Reversal of atypical depression, sleepiness, and REM-sleep propensity in narcolepsy with bupropion. Author(s): Rye DB, Dihenia B, Bliwise DL. Source: Depression and Anxiety. 1998; 7(2): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9614600&dopt=Abstract
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Review of regulations and guidelines for commercial and noncommercial drivers with sleep apnea and narcolepsy. Author(s): Pakola SJ, Dinges DF, Pack AI. Source: Sleep. 1995 November; 18(9): 787-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8638073&dopt=Abstract
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Ritanserin, a 5-HT2 receptor blocker, as add-on treatment in narcolepsy. Author(s): Lammers GJ, Arends J, Declerck AC, Kamphuisen HA, Schouwink G, Troost J. Source: Sleep. 1991 April; 14(2): 130-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1678203&dopt=Abstract
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RTMS induces brief events of muscle atonia in patients with narcolepsy. Author(s): Hungs M, Mottaghy FM, Sparing R, Zuchner S, Boroojerdi B, Topper R. Source: Sleep. 2000 December 15; 23(8): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145324&dopt=Abstract
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Salivary secretions: narcolepsy and central nervous system stimulants. Author(s): Nordgarden H, Lamkin M, Oppenheim FG, Storhaug K, Jensen JL. Source: Journal of Dental Research. 1998 October; 77(10): 1817-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9786638&dopt=Abstract
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Scheduled naps in the management of daytime sleepiness in narcolepsy-cataplexy. Author(s): Mullington J, Broughton R. Source: Sleep. 1993 August; 16(5): 444-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8378686&dopt=Abstract
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Schizophrenia, narcolepsy, and HLA-DR15, DQ6. Author(s): Douglass AB, Shipley JE, Haines RF, Scholten RC, Dudley E, Tapp A. Source: Biological Psychiatry. 1993 December 1; 34(11): 773-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8292681&dopt=Abstract
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Screening for anti-ganglioside antibodies in hypocretin-deficient human narcolepsy. Author(s): Overeem S, Geleijns K, Garssen MP, Jacobs BC, van Doorn PA, Lammers GJ. Source: Neuroscience Letters. 2003 April 24; 341(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676332&dopt=Abstract
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Secondary narcolepsy in a case of multiple sclerosis. Author(s): Rao DG, Singhal BS. Source: J Assoc Physicians India. 1997 April; 45(4): 321-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521093&dopt=Abstract
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Secondary narcolepsy in children with brain tumors. Author(s): Marcus CL, Trescher WH, Halbower AC, Lutz J. Source: Sleep. 2002 June 15; 25(4): 435-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071545&dopt=Abstract
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Segregation of HLA genes in multicase narcolepsy families. Author(s): Mayer G, Lattermann A, Mueller-Eckhardt G, Svanborg E, Meier-Ewert K. Source: Journal of Sleep Research. 1998 June; 7(2): 127-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9682185&dopt=Abstract
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Selegiline in the treatment of narcolepsy. Author(s): Hublin C, Partinen M, Heinonen EH, Puukka P, Salmi T. Source: Neurology. 1994 November; 44(11): 2095-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7969965&dopt=Abstract
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Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy. Author(s): Fehr C, Schleicher A, Szegedi A, Anghelescu I, Klawe C, Hiemke C, Dahmen N. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2001 July; 25(5): 965-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444684&dopt=Abstract
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Severity of narcolepsy among French of different ethnic origins (south of France and Martinique). Author(s): Dauvilliers Y, Bazin M, Ondze B, Bera O, Bazin M, Besset A, Billiard M. Source: Sleep. 2002 February 1; 25(1): 50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833861&dopt=Abstract
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Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is associated with response to modafinil. Author(s): Dauvilliers Y, Neidhart E, Billiard M, Tafti M. Source: The Pharmacogenomics Journal. 2002; 2(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990384&dopt=Abstract
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Significant association of a single nucleotide polymorphism in the tumor necrosis factor-alpha (TNF-alpha) gene promoter with human narcolepsy. Author(s): Hohjoh H, Nakayama T, Ohashi J, Miyagawa T, Tanaka H, Akaza T, Honda Y, Juji T, Tokunaga K. Source: Tissue Antigens. 1999 August; 54(2): 138-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10488740&dopt=Abstract
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Significant association of the tumor necrosis factor receptor 2 (TNFR2) gene with human narcolepsy. Author(s): Hohjoh H, Terada N, Kawashima M, Honda Y, Tokunaga K. Source: Tissue Antigens. 2000 November; 56(5): 446-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144293&dopt=Abstract
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Sleep and narcolepsy. Author(s): Culebras A. Source: Archives of Neurology. 1999 January; 56(1): 117-8. Erratum In: Arch Neurol 1999 May; 56(5): 632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9923772&dopt=Abstract
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Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs. Author(s): Mitler MM, Walsleben J, Sangal RB, Hirshkowitz M. Source: Electroencephalography and Clinical Neurophysiology. 1998 July; 107(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743270&dopt=Abstract
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Sleep-related spells associated with parasomnias and narcolepsy. Author(s): Aldrich MS. Source: Seminars in Neurology. 1995 June; 15(2): 194-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7481140&dopt=Abstract
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Solving the mysteries of narcolepsy: the hypocretin story. Author(s): Silber MH, Rye DB. Source: Neurology. 2001 June 26; 56(12): 1616-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425923&dopt=Abstract
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Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy: a pilot study. Author(s): Larrosa O, de la Llave Y, Bario S, Granizo JJ, Garcia-Borreguero D. Source: Sleep. 2001 May 1; 24(3): 282-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322710&dopt=Abstract
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Striatal dopamine D2 receptors in patients with narcolepsy measured with PET and 11C-raclopride. Author(s): Khan N, Antonini A, Parkes D, Dahlitz MJ, Meier-Ewert K, Weindl A, Leenders KL. Source: Neurology. 1994 November; 44(11): 2102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7969966&dopt=Abstract
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Subjective sleepiness ratings (Epworth sleepiness scale) do not reflect the same parameter of sleepiness as objective sleepiness (maintenance of wakefulness test) in patients with narcolepsy. Author(s): Sangal RB, Mitler MM, Sangal JM. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 December; 110(12): 2131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616118&dopt=Abstract
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The effect of regularly scheduled naps on sleep attacks and excessive daytime sleepiness associated with narcolepsy. Author(s): Rogers AE, Aldrich MS. Source: Nursing Research. 1993 March-April; 42(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8455986&dopt=Abstract
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The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Author(s): Silber MH, Krahn LE, Olson EJ, Pankratz VS. Source: Sleep. 2002 March 15; 25(2): 197-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902429&dopt=Abstract
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The genetics of narcolepsy. Author(s): Chabas D, Taheri S, Renier C, Mignot E. Source: Annual Review of Genomics and Human Genetics. 2003; 4: 459-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527309&dopt=Abstract
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The history of narcolepsy and other sleep disorders. Author(s): Dement WC. Source: Journal of the History of the Neurosciences. 1993 April; 2(2): 121-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11618448&dopt=Abstract
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The HTR1B 861G>C receptor polymorphism among patients suffering from alcoholism, major depression, anxiety disorders and narcolepsy. Author(s): Fehr C, Grintschuk N, Szegedi A, Anghelescu I, Klawe C, Singer P, Hiemke C, Dahmen N. Source: Psychiatry Research. 2000 December 4; 97(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104852&dopt=Abstract
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The importance of HLA DQB1*0602 typing in Slovene patients with narcolepsy. Author(s): Dolenc-Grosel L, Vodusek DB. Source: Cellular & Molecular Biology Letters. 2002; 7(2): 359-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097985&dopt=Abstract
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The neurobiology of narcolepsy-cataplexy syndrome. Author(s): Aldrich MS. Source: Int J Neurol. 1991-1992; 25-26: 29-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980061&dopt=Abstract
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The neurobiology of narcolepsy-cataplexy. Author(s): Aldrich MS. Source: Progress in Neurobiology. 1993 November; 41(5): 533-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8284435&dopt=Abstract
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The neurobiology, diagnosis, and treatment of narcolepsy. Author(s): Scammell TE. Source: Annals of Neurology. 2003 February; 53(2): 154-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557281&dopt=Abstract
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The prevalence of narcolepsy among Chinese in Hong Kong. Author(s): Wing YK, Li RH, Lam CW, Ho CK, Fong SY, Leung T. Source: Annals of Neurology. 2002 May; 51(5): 578-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112103&dopt=Abstract
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The prevalence of narcolepsy: an epidemiological study of the Finnish Twin Cohort. Author(s): Hublin C, Kaprio J, Partinen M, Koskenvuo M, Heikkila K, Koskimies S, Guilleminault C. Source: Annals of Neurology. 1994 June; 35(6): 709-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8210228&dopt=Abstract
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The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Author(s): Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, Vankova J, Black J, Harsh J, Bassetti C, Schrader H, Nishino S. Source: Archives of Neurology. 2002 October; 59(10): 1553-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374492&dopt=Abstract
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The role of hypocretins (orexins) in sleep regulation and narcolepsy. Author(s): Taheri S, Zeitzer JM, Mignot E. Source: Annual Review of Neuroscience. 2002; 25: 283-313. Epub 2002 March 20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052911&dopt=Abstract
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The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Author(s): Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E. Source: Cell. 1999 August 6; 98(3): 365-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458611&dopt=Abstract
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The treatment of narcolepsy. Author(s): Broughton RJ. Source: Suppl Clin Neurophysiol. 2000; 53: 371-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741023&dopt=Abstract
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Time-on-task decrements in “steer clear” performance of patients with sleep apnea and narcolepsy. Author(s): Findley LJ, Suratt PM, Dinges DF. Source: Sleep. 1999 September 15; 22(6): 804-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10505827&dopt=Abstract
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Tranylcypromine in narcolepsy. Author(s): Gernaat HB, Haffmans PM, Knegtering H, Birkenhager TK. Source: Pharmacopsychiatry. 1995 May; 28(3): 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7568373&dopt=Abstract
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Treatment modalities for narcolepsy. Author(s): Fry JM. Source: Neurology. 1998 February; 50(2 Suppl 1): S43-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9484423&dopt=Abstract
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Treatment of narcolepsy with methamphetamine. Author(s): Mitler MM, Hajdukovic R, Erman MK. Source: Sleep. 1993 June; 16(4): 306-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8341891&dopt=Abstract
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Twin studies in narcolepsy. Author(s): Partinen M, Hublin C, Kaprio J, Koskenvuo M, Guilleminault C. Source: Sleep. 1994 December; 17(8 Suppl): S13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701193&dopt=Abstract
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Ultradian aspects of sleep in narcolepsy. Author(s): Nobili L, Ferrillo F, Besset A, Rosadini G, Schiavi G, Billiard M. Source: Neurophysiologie Clinique = Clinical Neurophysiology. 1996; 26(1): 51-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8657098&dopt=Abstract
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Undetectable CSF level of orexin A (hypocretin-1) in a HLA-DR2 negative patient with narcolepsy-cataplexy. Author(s): Dalal MA, Schuld A, Pollmacher T. Source: Journal of Sleep Research. 2002 September; 11(3): 273. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220324&dopt=Abstract
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Undetectable levels of CSF hypocretin-1 (orexin-A) in two prepubertal boys with narcolepsy. Author(s): Tsukamoto H, Ishikawa T, Fujii Y, Fukumizu M, Sugai K, Kanbayashi T. Source: Neuropediatrics. 2002 February; 33(1): 51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930279&dopt=Abstract
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Use of modafinil in the treatment of narcolepsy: a long term follow-up study. Author(s): Besset A, Chetrit M, Carlander B, Billiard M. Source: Neurophysiologie Clinique = Clinical Neurophysiology. 1996; 26(1): 60-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8657099&dopt=Abstract
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Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy. Author(s): Aldrich MS, Chervin RD, Malow BA. Source: Sleep. 1997 August; 20(8): 620-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9351129&dopt=Abstract
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Vasotocin, melatonin and narcolepsy: possible involvement of the pineal gland in its patho-physiological mechanism. Author(s): Pavel S, Goldstein R, Petrescu M. Source: Peptides. 1980 Winter; 1(4): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7301633&dopt=Abstract
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Vigilance and automobile accidents in patients with sleep apnea or narcolepsy. Author(s): Findley L, Unverzagt M, Guchu R, Fabrizio M, Buckner J, Suratt P. Source: Chest. 1995 September; 108(3): 619-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7656606&dopt=Abstract
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Vigilance performance and autonomic function in narcolepsy: effects of central stimulants. Author(s): Levander S, Sachs C. Source: Psychophysiology. 1985 January; 22(1): 24-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2858111&dopt=Abstract
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Viloxazine hydrochloride in narcolepsy: a preliminary report. Author(s): Guilleminault C, Mancuso J, Salva MA, Hayes B, Mitler M, Poirier G, Montplaisir J. Source: Sleep. 1986; 9(1 Pt 2): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3704453&dopt=Abstract
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Visual P300 latency predicts treatment response to modafinil in patients with narcolepsy. Author(s): Sangal RB, Sangal JM, Belisle C. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 June; 110(6): 1041-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402091&dopt=Abstract
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Voxel-based morphometry in hypocretin-deficient narcolepsy. Author(s): Overeem S, Steens SC, Good CD, Ferrari MD, Mignot E, Frackowiak RS, van Buchem MA, Lammers GJ. Source: Sleep. 2003 February 1; 26(1): 44-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627731&dopt=Abstract
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CHAPTER 2. NUTRITION AND NARCOLEPSY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and narcolepsy.
Finding Nutrition Studies on Narcolepsy 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 “narcolepsy” (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 “narcolepsy” (or a synonym): •
Bright white light does not improve narcoleptic symptoms. Author(s): Neurological Hospital, Schwalmstadt-Treysa, Federal Republic of Germany. Source: Hajek, M Meier Ewert, K Wirz Justice, A Tobler, I Arendt, J Dick, H Fink, G EurArch-Psychiatry-Neurol-Sci. 1989; 238(4): 203-7 0175-758X
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Central administration of vitamin B12 aggravates cataplexy in canine narcolepsy. Author(s): Sleep Disorders and Research Center, Stanford University, Palo Alto, CA 94304, USA. Source: Honda, K Riehl, J Inoue, S Mignot, E Nishino, S Neuroreport. 1997 December 22; 8(18): 3861-5 0959-4965
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Cholinergic mechanisms in canine narcolepsy--I. Modulation of cataplexy via local drug administration into the pontine reticular formation. Author(s): Stanford University Sleep Disorders Research Center, Palo Alto, CA 94304. Source: Reid, M S Tafti, M Geary, J N Nishino, S Siegel, J M Dement, W C Mignot, E Neuroscience. 1994 April; 59(3): 511-22 0306-4522
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Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy. Author(s): Stanford Sleep Disorders Center, Stanford University School of Medicine, 94304., Palo Alto, CA 94304, USA. Source: Riehl, J Honda, K Kwan, M Hong, J Mignot, E Nishino, S Neuropsychopharmacology. 2000 July; 23(1): 34-45 0893-133X
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Dopamine D2 mechanisms in canine narcolepsy. Author(s): Stanford Sleep Disorders Research Center, Palo Alto, California 94304. Source: Nishino, S Arrigoni, J Valtier, D Miller, J D Guilleminault, C Dement, W C Mignot, E J-Neurosci. 1991 September; 11(9): 2666-71 0270-6474
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Effect of L-dopa on periodic movements in sleep in narcolepsy. Source: Bedard, M A Montplaisir, J Godbout, R Eur-Neurol. 1987; 27(1): 35-8 0014-3022
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Effectiveness of yohimbine in treating narcolepsy. Author(s): Eastern Virginia Medical School Sleep Disorders Center, Norfolk 23507. Source: Wooten, V South-Med-J. 1994 November; 87(11): 1065-6 0038-4348
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Effects of bromocriptine in human narcolepsy. Author(s): Centre d'Etude du Sommeil, Hopital Sacre-Coeur, Montreal, Quebec, Canada. Source: Boivin, D B Montplaisir, J Lambert, C Clin-Neuropharmacol. 1993 April; 16(2): 120-6 0362-5664
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Effects of central alpha-2 adrenergic compounds on canine narcolepsy, a disorder of rapid eye movement sleep. Author(s): Stanford Sleep Disorders Research Center, Palo Alto, California. Source: Nishino, S Haak, L Shepherd, H Guilleminault, C Sakai, T Dement, W C Mignot, E J-Pharmacol-Exp-Ther. 1990 June; 253(3): 1145-52 0022-3565
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Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures. Author(s): Department of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205. Source: Scrima, L Hartman, P G Johnson, F H Hiller, F C Biol-Psychiatry. 1989 August; 26(4): 331-43 0006-3223
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Familial occurrence of narcolepsy in miniature horses. Author(s): School of Veterinary Medicine, University of Wisconsin, Madison 53706. Source: Lunn, D P Cuddon, P A Shaftoe, S Archer, R M Equine-Vet-J. 1993 November; 25(6): 483-7 0425-1644
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Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. Author(s): Department of Neurology, Leiden University Hospital, The Netherlands. Source: Lammers, G J Arends, J Declerck, A C Ferrari, M D Schouwink, G Troost, J Sleepage 1993 April; 16(3): 216-20 0161-8105
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Heterozygosity at the canarc-1 locus can confer susceptibility for narcolepsy: induction of cataplexy in heterozygous asymptomatic dogs after administration of a combination of drugs acting on monoaminergic and cholinergic systems. Author(s): Stanford University Sleep Disorders Center, Palo Alto, California 94304. Source: Mignot, E Nishino, S Sharp, L H Arrigoni, J Siegel, J M Reid, M S Edgar, D M Ciaranello, R D Dement, W C J-Neurosci. 1993 March; 13(3): 1057-64 0270-6474
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L-tyrosine in the treatment of narcolepsy. Source: Roufs, J B Med-Hypotheses. 1990 December; 33(4): 269-73 0306-9877
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Narcolepsy in a 2-year-old boy. Author(s): Children's Hospital, Ladywood, Birmingham. Source: Winter, E Prendergast, M Green, A Dev-Med-Child-Neurol. 1996 April; 38(4): 356-9 0012-1622
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Narcolepsy. Author(s): School of Nursing, University of Pennsylvania, 420 Guardian Drive, Philadelphia, PA 19104, USA.
[email protected] Source: Rogers, A E Dreher, H M Nurs-Clin-North-Am. 2002 December; 37(4): 675-92 0029-6465
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Neurochemical perspectives of the narcoleptic syndrome. Author(s): University of Arizona. Source: Sandyk, R Bamford, C Labadie, E Int-J-Neurosci. 1988 January; 38(1-2): 21-30 0020-7454
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Neuronal activity in the cholinoceptive basal forebrain of freely moving narcoleptic dobermans. Author(s): Center for Narcolepsy, Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Palo Alto, CA 94304, USA. Source: Nishino, S Honda, K Riehl, J Okura, M Mignot, E Neuroreport. 1998 November 16; 9(16): 3653-61 0959-4965
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Nocturnal gamma-hydroxybutyrate. Effect on periodic leg movements and sleep organization of narcoleptic patients. Author(s): Centre d'etude du sommeil, Hopital du Sacre-Coeur, Montreal, Quebec, Canada. Source: Bedard, M A Montplaisir, J Godbout, R Lapierre, O Clin-Neuropharmacol. 1989 February; 12(1): 29-36 0362-5664
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Non-pharmacological approaches to the treatment of narcolepsy. Author(s): Unite des Troubles du Sommeil, Hopital de la Salpetriere, Paris, France. Source: Garma, L Marchand, F Sleepage 1994 December; 17(8 Suppl): S97-102 0161-8105
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Platelet alpha 2 adrenoceptors in human and canine narcolepsy. Author(s): Sleep Research Center, Stanford University School of Medicine, Palo Alto, CA 94304.
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Source: Valtier, D Nishino, S Guilleminault, C Dement, W C Mignot, E Biol-Psychiatry. 1991 February 15; 29(4): 376-82 0006-3223 •
Prostaglandin E2 and its methyl ester reduce cataplexy in canine narcolepsy. Author(s): Sleep Disorders Center, Stanford University School of Medicine, Palo Alto, CA 94304. Source: Nishino, S Mignot, E Fruhstorfer, B Dement, W C Hayaishi, O Proc-Natl-AcadSci-U-S-A. 1989 April; 86(7): 2483-7 0027-8424
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Relative efficacy of drugs for the treatment of sleepiness in narcolepsy. Author(s): Scripps Clinic and Research Foundation, La Jolla, California 92037. Source: Mitler, M M Hajdukovic, R Sleepage 1991 June; 14(3): 218-20 0161-8105
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Selegiline in narcolepsy. Author(s): University Department of Neurology, King's College School of Medicine, London, England. Source: Roselaar, S E Langdon, N Lock, C B Jenner, P Parkes, J D Sleepage 1987 October; 10(5): 491-5 0161-8105
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Selegiline in the treatment of narcolepsy. Author(s): Department of Neurology, University of Helsinki, Finland. Source: Hublin, C Partinen, M Heinonen, E H Puukka, P Salmi, T Neurology. 1994 November; 44(11): 2095-101 0028-3878
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Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is associated with response to modafinil. Author(s): Neurologie B, Hjpital Gui-de-Chauliac, Montpellier, France. Source: Dauvilliers, Y Neidhart, E Billiard, M Tafti, M Pharmacogenomics-J. 2002; 2(1): 65-8 1470-269X
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The cardioacceleratory response to arecoline infusion during sleep in narcoleptic subjects and controls. Source: Baruch, H L Kelwala, S Kapen, S Sleepage 1987 June; 10(3): 272-8 0161-8105
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The effect of naloxone on the symptoms of narcolepsy. Source: Sonka, K Roth, B Posmurova, M Agressologie. 1989 February; 30(2): 93-6 00021148
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The effects of L-dopa on excessive daytime sleepiness in narcolepsy. Author(s): Sleep Disorders Center, Sacre-Coeur Hospital, Montreal, Quebec, Canada. Source: Boivin, D B Montplaisir, J Neurology. 1991 August; 41(8): 1267-9 0028-3878
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Treatment of narcolepsy with L-tyrosine. Author(s): Unite Clinique de Psychiatrie Biologique, Hopital du Vinatier, Bron, France. Source: Mouret, J Lemoine, P Sanchez, P Robelin, N Taillard, J Canini, F Lancet. 1988 December 24-31; 2(8626-8627): 1458-9 0140-6736
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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CHAPTER 3. ALTERNATIVE MEDICINE AND NARCOLEPSY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to narcolepsy. 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 narcolepsy 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 “narcolepsy” (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 narcolepsy: •
A note on distinguishing between hypnotic “sleep” and narcoleptic “sleep”. Author(s): McCord H. Source: J Am Soc Psychosom Dent Med. 1967 April; 14(2): 55-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5229395&dopt=Abstract
•
A parasomnia overlap disorder involving sleepwalking, sleep terrors, and REM sleep behavior disorder in 33 polysomnographically confirmed cases. Author(s): Schenck CH, Boyd JL, Mahowald MW. Source: Sleep. 1997 November; 20(11): 972-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9456462&dopt=Abstract
•
Attentive and preattentive processing in narcolepsy as revealed by event-related potentials (ERPs). Author(s): Naumann A, Bierbrauer J, Przuntek H, Daum I.
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Source: Neuroreport. 2001 September 17; 12(13): 2807-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588581&dopt=Abstract •
Circadian distribution of motor activity and immobility in narcolepsy: assessment with continuous motor activity monitoring. Author(s): Middelkoop HA, Lammers GJ, Van Hilten BJ, Ruwhof C, Pijl H, Kamphuisen HA. Source: Psychophysiology. 1995 May; 32(3): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7784537&dopt=Abstract
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Clinical and polygraphic study of the cataplectic attacks. Author(s): Corfariu O, Popoviciu L. Source: Rev Roum Neurol Psychiatr. 1974; 11(1): 3-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4364223&dopt=Abstract
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Complex event-related potentials (P300 and CNV) and MSLT in the assessment of excessive daytime sleepiness in narcolepsy-cataplexy. Author(s): Aguirre M, Broughton RJ. Source: Electroencephalography and Clinical Neurophysiology. 1987 October; 67(4): 298-316. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2441963&dopt=Abstract
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EEG activation with Dimefline hydrochloride. Author(s): Kazamatsuri H. Source: Folia Psychiatr Neurol Jpn. 1969; 23(1): 15-23. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4390282&dopt=Abstract
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Effects of startle and laughter in cataplectic subjects: a neurophysiological study between attacks. Author(s): Lammers GJ, Overeem S, Tijssen MA, van Dijk JG. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 July; 111(7): 1276-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880803&dopt=Abstract
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Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome. Author(s): Howard RJ, Ellis C, Bullmore ET, Brammer M, Mellers JD, Woodruff PW, David AS, Simmons A, Williams SC, Parkes JD. Source: Magnetic Resonance Imaging. 1996; 14(9): 1013-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9070991&dopt=Abstract
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Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil.
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Author(s): Ellis CM, Monk C, Simmons A, Lemmens G, Williams SC, Brammer M, Bullmore E, Parkes JD. Source: Journal of Sleep Research. 1999 June; 8(2): 85-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389090&dopt=Abstract •
Hypnotherapy for narcolepsy. Author(s): Schneck JM. Source: Int J Clin Exp Hypn. 1980 April; 28(2): 95-100. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7364526&dopt=Abstract
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Hypnotherapy in the control of cataplexy in a narcoleptic subject. Author(s): Price R. Source: Am J Clin Hypn. 1987 January; 29(3): 201-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3825977&dopt=Abstract
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Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. Author(s): Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 September 15; 21(18): 7273-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549737&dopt=Abstract
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Immobility reactions: a modified classification. Author(s): Reese WG, Angel C, Newton JE. Source: Pavlov J Biol Sci. 1984 July-September; 19(3): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6541777&dopt=Abstract
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Medical-psychological implications of recent sleep research. Author(s): Pearlman CA, Greenberg R. Source: Psychiatry Med. 1970 October; 1(4): 261-76. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4402296&dopt=Abstract
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Method of promoting blood circulation to eliminate stasis in treatment of narcolepsy. Report of 4 cases. Author(s): Chen JH, Gao Y. Source: J Tradit Chin Med. 1982 March; 2(1): 67-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6765692&dopt=Abstract
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Muscarinic cholinergic receptors in human narcolepsy: a PET study. Author(s): Sudo Y, Suhara T, Honda Y, Nakajima T, Okubo Y, Suzuki K, Nakashima Y, Yoshikawa K, Okauchi T, Sasaki Y, Matsushita M.
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Source: Neurology. 1998 November; 51(5): 1297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818849&dopt=Abstract •
Narcolepsy: pathogenesis and nursing care. Author(s): Bergstrom DL, Keller C. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1992 June; 24(3): 153-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1645038&dopt=Abstract
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Near-fatal gamma-butyrolactone intoxication--first report in the UK. Author(s): Dupont P, Thornton J. Source: Human & Experimental Toxicology. 2001 January; 20(1): 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339620&dopt=Abstract
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Neurological aspects of hallucinogenic drugs. Author(s): Logan WJ. Source: Adv Neurol. 1975; 13: 47-78. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=814800&dopt=Abstract
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Non-pharmacological approaches to the treatment of narcolepsy. Author(s): Garma L, Marchand F. Source: Sleep. 1994 December; 17(8 Suppl): S97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701208&dopt=Abstract
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Parasomnias: epidemiology and management. Author(s): Wills L, Garcia J. Source: Cns Drugs. 2002; 16(12): 803-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421114&dopt=Abstract
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RTMS induces brief events of muscle atonia in patients with narcolepsy. Author(s): Hungs M, Mottaghy FM, Sparing R, Zuchner S, Boroojerdi B, Topper R. Source: Sleep. 2000 December 15; 23(8): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145324&dopt=Abstract
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Sleep disorders. Author(s): Olejniczak PW, Fisch BJ. Source: The Medical Clinics of North America. 2003 July; 87(4): 803-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834150&dopt=Abstract
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Sleep disorders. Author(s): Silber MH.
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Source: Neurologic Clinics. 2001 February; 19(1): 173-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471763&dopt=Abstract •
Sleep disorders. Author(s): Yousaf F, Sedgwick P. Source: Br J Hosp Med. 1996 March 20-April 2; 55(6): 353-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8696635&dopt=Abstract
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Sleep paralysis and hallucinosis. Author(s): Stores G. Source: Behavioural Neurology. 1998; 11(2): 109-112. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568409&dopt=Abstract
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Stimulus-induced drop episodes in Coffin-Lowry syndrome. Author(s): Nelson GB, Hahn JS. Source: Pediatrics. 2003 March; 111(3): E197-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612271&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/
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The following is a specific Web list relating to narcolepsy; 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 Asthma Source: Prima Communications, Inc.www.personalhealthzone.com Narcolepsy Source: Integrative Medicine Communications; www.drkoop.com Sleep Apnea Source: Integrative Medicine Communications; www.drkoop.com
•
Herbs and Supplements Ephedra Source: Prima Communications, Inc.www.personalhealthzone.com Methylphenidate Source: Healthnotes, Inc.; www.healthnotes.com Mixed Amphetamines Source: Healthnotes, Inc.; www.healthnotes.com Tyrosine Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON NARCOLEPSY Overview In this chapter, we will give you a bibliography on recent dissertations relating to narcolepsy. 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 “narcolepsy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on narcolepsy, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Narcolepsy 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 narcolepsy. 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: •
An Investigation of the Continuity and Alternative Channels Hypotheses in Sleep Paralysis and Narcolepsy by McNulty, Stacey A.; PhD from Carleton University (Canada), 2002, 253 pages http://wwwlib.umi.com/dissertations/fullcit/NQ71941
•
Having Narcolepsy: the Experience and Treatment in Children, Adolescents and Young Adults by Zafarlotfi, Susan, PhD from City University of New York, 1997, 210 pages http://wwwlib.umi.com/dissertations/fullcit/9732989
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Performance Impairment in Relation to Concomitant Physiological Vigilance Levels and Subjective States in Patients with Narcolepsy Compared to Matched Controls by Valley, Victoria; PhD from University of Ottawa (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK48648
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Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND NARCOLEPSY Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning narcolepsy.
Recent Trials on Narcolepsy The following is a list of recent trials dedicated to narcolepsy.8 Further information on a trial is available at the Web site indicated. •
Safety and efficacy of Xyrem oral solution (sodium oxybate) compared with placebo in narcoleptic patients Condition(s): Narcolepsy Study Status: This study is currently recruiting patients. Sponsor(s): Orphan Medical Purpose - Excerpt: The initial portion of the protocol involves discontinuing any medications for cataplexy that the patient may be taking. Subsequently, the patient is prescribed a dose of oral solution of study drug or placebo over a 10-11 week period. During the trial, narcolepsy symptoms will be evaluated. Participants are allowed to continue using stimulant medications at constant doses during the study. A total of 1 to 3 daytime visits in addition to 4 overnight visits to the sleep center will be required to complete the study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049803
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Sleep Disorders of Patients with Diseases of the Nervous System Condition(s): Hypersomnia; Narcolepsy; Nervous System Disease; Sleep Disorder
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These are listed at www.ClinicalTrials.gov.
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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to assist training doctors about different diseases of the nervous system affecting sleep. Patients selected to participate in this study will have any of a variety of sleep disorders. They will undergo several tests including an overnight recording of brain activity, eye movement, leg movement, breathing, heart rate, and other measures. Results of these tests will be used to better understand diseases causing sleep disorders and may be used to develop better treatments for them. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001664 •
Trial Comparing Effects of Xyrem taken Orally and Modafinil with Placebo in Treating Daytime Sleepiness in Narcolepsy Condition(s): Narcolepsy Study Status: This study is currently recruiting patients. Sponsor(s): Orphan Medical Purpose - Excerpt: This study will be conducted as a randomized, double blind, doubledummy, placebo-controlled, parallel-group trial in patients diagnosed with narcolepsy. Volunteers for this trial will be required to make 5 visits over up to 14 weeks to a participating expert physician practitioner for various sleep and narcolepsy evaluations and diaries will also be collected. Participants will take assigned medications during the course of the trial. Subjects will have a 25% probability of receiving placebo for both drugs (modafinil and Xyrem). All subject volunteers must meet criteria for narcolepsy and have evidence of daytime sleepiness. Patients will not incur any personal medical expenses due to participation in this trial. The sponsor is covering all visit costs not covered by insurance and there are some funds for patient expenses such as travel. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066170
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “narcolepsy” (or synonyms).
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While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON NARCOLEPSY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “narcolepsy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on narcolepsy, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Narcolepsy By performing a patent search focusing on narcolepsy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on narcolepsy: •
Bis (benzimidazole) derivatives serving as potassium blocking agents Inventor(s): Jensen; Bo Skaaning (Copenhagen S, DK), Olesen; S.o slashed.ren Peter (Klampenborg, DK), Peters; Dan (Arlov, DK), Str.o slashed.b.ae butted.k; Dorte (Farum, DK), Teuber; Lene (V.ae butted.rl.o slashed.se, DK) Assignee(s): Neurosearch A/S (Ballerup, DK) Patent Number: 6,194,447 Date filed: July 2, 1999 Abstract: This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions.Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Excerpt(s): This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Ion channels are transmembrane proteins, which catalyze the transport of inorganic ions across cell membranes. The ion channels participate in processes as diverse as the generation and timing of action potentials, synaptic transmissions, secretion of hormones, contraction of muscles, etc. Web site: http://www.delphion.com/details?pn=US06194447__
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Compounds with high monoamine transporter affinity Inventor(s): Blundell; Paul (Winchester, MA), Madras; Bertha K. (Newton, MA), Meltzer; Peter C. (Lexington, MA), Wang; Pinglang (Cambridge, MA) Assignee(s): Organix, Inc. (Woburn, MA), President and Fellows of Harvard College (Cambridge, MA) Patent Number: 6,525,206 Date filed: October 17, 2000 Abstract: Featured compounds have high monoamine transport affinity and are characterized by one of the following two general formulas set out above. The compounds bind selectively or non-selectively to monoamine transporters. The compounds are useful to treat various medical indications including attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke, and narcolepsy. Excerpt(s): This invention relates to novel compositions with affinity for a monoamine transporter, such as the dopamine, norepinephrine, or serotonin transporter, in brain and in peripheral tissues. Monoamine transporters play a variety of roles, and compounds with affinity for the monoamine transporters have been proposed for therapy and/or diagnosis of medical indications that include (but are not limited to) attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke, and narcolepsy. The dopamine transporter (DAT) in particular is a primary mechanism for terminating the effects of synaptic dopamine and maintaining homeostatic levels of extracellular dopamine in brain. Giros et al., Nature 379: 696-612 (1996). The dopamine transporter is a principal target of therapeutic and psychostimulant drugs of abuse. For example, the dopamine transporter is an important target of drugs (including methylphenidate, pemoline, amphetamine and bupropion) used to treat ADHD. Seeman and Madras, Mol. Psychiatry 3:386-396 (1998); Cyr and Brown, Drugs, 56:215-223 (1998); Biederman, J. Clin. Psychiatry 59: 4-16 (1998); Riggs et al., J. Am Acad. Child Adolesc. Psychiatry 37:1271-1278 (1999). The dopamine transporter is also a principal target of brain imaging agents used, for example, diagnostically. Web site: http://www.delphion.com/details?pn=US06525206__
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Method and composition for treating obesity, drug abuse, and narcolepsy Inventor(s): Hohenwarter; Mark (Mobile, AL) Assignee(s): Serotonin Industries of Charleston (Charleston, SC) Patent Number: 4,843,071 Date filed: December 5, 1986 Abstract: Compositions and methods are disclosed for the treatment of obesity, depression, drug abuse, and narcolepsy. The compositions comprise a norepinephrine precursor such as L-tyrosine or L-phenylalanine in combination with a norepinephrine re-uptake inhibitor such as desipramine. In another embodiment of the invention, the compositions further comprise enzymatic cofactors for the biosynthesis of norepinephrine.
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Excerpt(s): This invention relates to compositions comprising a norepinephrine precursor, such as L-tyrosine or L-phenylalanine in combination with a norepinephrine re-uptake inhibitor such as desipramine. The compositions are useful in controlling obesity, depression, drug abuse, and narcolepsy in animals. The invention also relates to said compositions further comprising one or more enzymatic cofactors for the biosynthesis of norepinephrine. This invention further relates to a method of controlling obesity, depression, drug abuse, or narcolepsy in an animal comprising administering an effective amount of the compositions of this invention to said animal. The use of appetite supressants such as diethylproprion and phenylpropanolamine operate by directly and/or indirectly stimulating noradrenergic receptors in the brain. However, long-term use of these drugs is met with increasing tolerance in most patients, requiring increased dosage and more frequent administration to achieve continued appetite suppression. Tolerance to these products occurs as the result of a depletion of norepinephrine from storage sites in the neuron with the use of indirect-acting agents. Catecholamines are stored in subcellular granules and released by exocytosis in the adrenal medulla and sympathetic nerve endings. The biosynthesis of catecholamines proceeds from the amino acid phenylalanine which is sequentially hydroxylated to form tyrosine, then 3,4-dihydroxyphenylalanine (DOPA). DOPA is decarboxylated to form dopamine. Hydroxylation on the beta position of the side chain forms norepinephrine. Web site: http://www.delphion.com/details?pn=US04843071__ •
Methods and compositions for treating chronic disorders using optically pure (+)bupropion Inventor(s): McCullough; John R. (Hudson, MA), Rubin; Paul D. (Sudbury, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,458,374 Date filed: January 28, 1999 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided
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by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06458374__ •
Therapeutic uses of polymers and oligomers comprising gamma-hydroxybutyrate Inventor(s): Martin; David P. (Arlington, MA), Williams; Simon F. (Sherborn, MA) Assignee(s): Metabolix, Inc. (Cambridge, MA), Tepha, Inc. (Cambridge, MA) Patent Number: 6,623,730 Date filed: September 14, 2000 Abstract: Oligomers and polymer compositions are provided which comprise GHB and produce GHB after administration in vivo. Devices for the storage and delivery of these polymers and oligomers are also provided. These oligomers and polymer compositions are useful in a variety of applications. The compositions can be used therapeutically, for example, in the treatment of patients with narcolepsy, chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, alcoholism, drug addiction and withdrawal, Parkinson's disease and other neuropharmacological illnesses, hypertension, ischemia, circulatory collapse, radiation exposure, cancer, and myocardial infarction. Other uses for the compositions include anesthesia induction, sedation, growth hormone production, heightened sexual desire, anorectic effects, euphoria, smooth muscle relaxation, muscle mass production, and sleep, including rapid eye movement sleep. In a still further embodiment, the oligomers and polymers may be used to produce absence seizures. Excerpt(s): The present invention is generally in the field of therapeutic formulations for delivering gamma-hydroxybutyrate. Gamma-hydroxybutyrate ("GHB") is a naturally occurring substance that is widely distributed in the mammalian body, being present, for example, in the brain, kidney, heart, liver, lung and muscle (Nelson, et al., J. Neurochem., 37:1345-48 (1981)). When administered exogenously, GHB readily crosses the blood-brain barrier and penetrates the brain, producing a number of neuropharmacological effects. For over 35 years, GHB has been used as an intravenous agent for the induction of anesthesia and for long-term sedation, without serious sideeffects on circulation or respiration (Entholzner, et al., Anesthetist, 44:345-50 (1995)), and without an accompanying seizure-inducing activity in humans (Tunnicliff, Clinical Toxicology, 35:581-90 (1997)). Patients with chronic schizophrenia characterized by autism, inactivity, and apathy; catatonic schizophrenia; chronic schizophrenia with hallucination and delusion; atypical psychoses; and chronic brain syndrome due to trauma, as well as neurotic patients (Tanaka, et al., Folia Psychiatrica et Neurologica, 20:9-17 (1966)), have all been treated using GHB. It also has recently been suggested that GHB may be a suitable agent for total intravenous anesthesia in patients with coronary artery disease (Kleinschmidt, et al., Euro. J. Anesthesiology, 14:590-99 (1997)), as well as for sedation during spinal anesthesia (Kleinschmidt, et al., Euro. J. Anaesthesiology, 16:23-30 (1999)). In addition to these uses, GHB also is used to treat narcolepsy, a chronic sleep disorder that usually begins in adolescence or early adulthood and lasts hroughout life. Narcolepsy is characterized by sudden sleep attacks lasting usually from a few to thirty minutes, paralysis upon lying down or waking, visual or auditory hallucinations at the onset of sleep, and temporary loss of muscle tone while awake (cataplexy) or asleep. Treatment with GHB substantially reduces these signs and symptoms of narcolepsy in humans (Scharf, Sleep, 21:507-14 (1998)).
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Web site: http://www.delphion.com/details?pn=US06623730__ •
Treatment of narcolepsy with immunosuppressants Inventor(s): Boehmer; Lisa N. (Northridge, CA), Siegel; Jerome M. (Northridge, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,204,245 Date filed: September 17, 1999 Abstract: The invention provides compositions and methods for treatment of narcolepsy or isolated cataplexy. Such methods entail administering a therapeutically effective regime of at least one immunosuppressive agent. The methods are particularly useful for prophylactic and therapeutic treatment of narcolepsy or isolated cataplexy. Excerpt(s): This invention resides in the fields of neurology, immunology, and medicine and relates to the treatment of narcolepsy, and immunosuppressive agents and compositions useful therein. Narcolepsy is a disabling neurological disorder that was first recognized 118 years ago by Gelineau, J. B. (De la narcolepsie, Gazette des Hopitaux Paris (1880) 53: 626-628). For a review of narcolepsy, see generally Chokroverty, S. (ed.), Sleep Disorders Medicine: Basic Science, Technical Considerations, and Clinical Aspects, 2.sub.2 nd edition, Butterworth Heinemann, Boston, Mass. U.S.A. 1999; Aldrich, M., Sleep Medicine, Oxford University Press, New York, N.Y. U.S.A. 1999; Vgnotzas, A. N. et al., Annu. Rev. Med. (1999) 50:387-400; and Guillenminault, C., Narcolepsy Syndrome in Principles and Practice of Sleep Medicine, 2.sup.nd edition (Kryger, M. H., et al. (eds.), (W. B. Saunders Philadelphia, Pa. U.S.A. 1989), pages 338-246). The symptoms of narcolepsy include excessive daytime sleepiness (EDS), hypnagogic and hypnopompic hallucinations (hallucinations during transitions into and out of sleep, respectively), cataplexy (sudden and reversible loss of muscle tone), sleep paralysis (an inability to move at sleep onset or awakening) and REM sleep at sleep onset (Guilleminault, C. 1989). In narcoleptics, sleep occurs at inappropriate times and in dangerous and embarrassing situations. Although total sleep time is near normal, nighttime sleep is disrupted by frequent awakenings (Mitler, M. et al., Psych Clin. N. Amer. (1987) 10:593606). Cataplexy, a temporary, partial or complete paralysis due to a sudden loss of muscle tone, with unimpaired consciousness, is typically triggered by sudden strong emotions, such as those accompanying laughter, anger and embarrassment. In some patients, status cataplecticus, or periods of repetitive loss of muscle tone, occurs and can last for hours or days. Narcolepsy has also been reported to occur in other animals and has been most intensively studied in canines (Foutz, A. S., et al., (1979) Sleep 1:413-421; Nishino, S. and Mignot, E. (1997) Prog. Neurobiol. 52:27-78; Cederberg, R., et al., (1998) Vet. Rec. 142, 31-36). Canine narcolepsy in Doberman pinschers and Labrador Retrievers is transmitted as an apparently single gene autosomal recessive trait with full penetrance, canarc-1 (Foutz, A. S., et al., (1979) Sleep 1:413-421; Baker, T.L. and Dement, W. C. (1985), Canine narcolepsy-cataplexy syndrome: evidence for an inherited monoaminergic-cholinergic imbalance in Brain Mechanisms of Sleep, D. J. McGinty, R. Drucker-Colin, A. Morrison, and P. L. Parmeggiani, eds. (New York: Raven Press), pages 199-233). A large number of physiological and pharmacological studies have demonstrated a close similarity between human and canine narcolepsy (Baker, T. L. and Dement, W. C. (1985) and Nishino, S. and Mignot, E. (1997)). These animals have all the major symptoms defining narcolepsy in humans, including episodes of cataplexy. Canine narcoleptics also exhibit excessive daytime sleepiness and interrupted sleep periods (Kaitin, K. I. et al., Electroenceph. Clin. Neurophysiol. (1986) 64:447-454).
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Cholinergic antagonists block cataplexy in both canine and human narcoleptics (Delashaw et al., (1979) Exp. Neurology 66:745-757).alpha.1 blockers (such as prazosin) exacerbate cataplexy in dogs and humans and can produce status cataplecticus in both species (Mignot et al., (1988) Brain Res. 444:184-188; Guilleminault et al., (1988) The Lancet 2: 511). Drugs used to treat cataplexy and excessive sleepiness in humans are also effective in narcoleptics dogs (Baker and Dement, 1985). Narcolepsy usually does not develop until adolescence in humans, but it can be seen as early as three or as late as 45 years of age or older (Yoss and Daly, (1960) Pediatrics 25:1025-1033; Billiard, (1985) Ann. Clin.Res 17:220-226). The appearance of cataplexy, as a proxy variable for the onset of narcolepsy/cataplexy, in canine narcolepsy, develops between 4 and 24 weeks of age. Web site: http://www.delphion.com/details?pn=US06204245__ •
Treatment of sleep disorders Inventor(s): Kluger; Ronald (Don Mills, CA), Mamelak; Mortimer (Willowdale, CA) Assignee(s): University of Toronto - Innovations Foundation (Toronto, CA) Patent Number: 4,599,355 Date filed: August 6, 1984 Abstract: Sleep disorders in mammals, such as insomnia and narcolepsy, are treated by administering an effective amount of ethyl 4-acetoxybutanoate, or a closely related homolog thereof. Excerpt(s): This invention relates to treatment of sleep disorders, and chemotherapeutic compounds and compositions useful therein. Sleep disorders are a problem in a large portion of the population. Narcolepsy and insomnia are widely occurring. Safe, nonaddictive and long-lasting drugs that are effective are substantially unavailable. Each class of drug currently used for this purpose has major drawbacks. For example, barbiturates have addictive tendencies, act as depressants on the central nervous system, and can be lethal in improper dosages. Benzodiazepines are less effective, and tend to lose their sedative effect with continued use. Gammahydroxybutyrate is effective in treatment of narcolepsy, and is a very powerful muscle relaxant, but is of only short duration of action, e.g. 2-3 hours. This is a major drawback, since the patient needs to be continually re-awakened for further dosages. where X is a linear methylene chain of from 3-5 carbon atoms in length, R is selected from lower alkyl groups, aryl and aralkyl groups of 7-12 carbon atoms, and R.sup.1 is selected from lower alkyl groups and benzyl group. Web site: http://www.delphion.com/details?pn=US04599355__
Patent Applications on Narcolepsy As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to narcolepsy:
10
This has been a common practice outside the United States prior to December 2000.
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Human narcolepsy gene Inventor(s): Gulcher, Jeffrey; (Chicago, IL), Olafsdottir, Berglind Ran; (Eskihlid, IS) Correspondence: Alice O. Carroll, ESQ.; Hamilton, Brook, Smith & Reynolds, P.C.; Two Militia Drive; Lexington; MA; 02421-4799; US Patent Application Number: 20020146719 Date filed: September 24, 2001 Abstract: The gene for hypocretin (orexin) receptor 1 (HCRTR1), which is associated with narcolepsy, is disclosed. Also described are methods of diagnosis of narcolepsy, pharmaceutical compositions comprising nucleic acids comprising the HCRTR1 gene, as well as methods of therapy of narcolepsy. Excerpt(s): This application is a Continuation of U.S. Ser. No. 09/479,128, filed Jan. 7, 2000, which is a Continuation-in-Part of U.S. Ser. No. 09/379,083, filed Aug. 23, 1999, now abandoned, the entire teachings of both of which are incorporated herein by reference. Narcolepsy, a disorder which affects approximately 1 in 2,000 individuals, is characterized by daytime sleepiness, sleep fragmentation, and symptoms of abnormal rapid eye movement (REM) sleep that include cataplexy (loss of muscle tone), sleep paralysis, and hypnagogic hallucinations (Aldrich, M. S., Neurology 42:34-43 (1992); Siegel, J. M.,Cell 98:409-412 (1999)). In humans, susceptibility to narcolepsy has been associated with a specific human leukocyte antigen (HLA) alleles, including DQB1*0602 (Mignot, E., Neurology 50:S16-22 (1998); Kadotani, H. et al., Genome Res. 8:427-434 (1998); Faraco, J. et al., J. Hered. 90:129-132 (1999)); however, attempts to verify narcolepsy as an autoimmune disorder have failed (Mignot, E. et al., Adv. Neuroimmunol. 5:23-37 (1995); Mignot, E., Curr. Opin. Pulm. Med. 2:482-487 (1996)). In a canine model of narcolepsy, the disorder is transmitted as an autosomal recessive trait, canarc-1 (Foutz, A. S. et al, Sleep 1:413-421 91979); Baker, T. L. and Dement, W. C., Brain Mechanisms of Sleep (D. J. McGinty et al., eds.s, New York: canine major histocompatibility complex has been excluded (Mignot, E. et al., Proc. Natl. Acad. Sci. USA 88:3475-3478 (1991)). A mutation in the hypocretin (orexin) receptor 2 gene in canines has been identified in narcolepsy (Lin, L. et al.,Cell 98:365-376 (1999)); Hypocrexins/orexins (orexin-A and -B) are neuropeptides associated with regulation of food consumption (de Lecea, L., et al., Proc. Natl. Acad. Sci. USA 95:322-327 (1998); Sakurai, T. et al., Cell 92:573-585 (1998)) as well as other possible functions (Peyron, C. et al., J. Neurosci. 18:9996-10015 (1998)). Human cDNA of receptors for orexins have been cloned (Sakurai, T. et al.,Cell 92:573-585 (1998)), however, full human genes for the orexin receptors have not yet been identified. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of using and compositions comprising (-) sibutramine optionally in combination with other pharmacologically active compounds Inventor(s): Jerussi, Thomas P.; (Framingham, MA), Young, James W.; (Palo Alto, CA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020006963 Date filed: January 29, 2001
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Abstract: This invention encompasses methods for the treatment and prevention of disorders that include, but are not limited to, eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.The invention further encompasses pharmaceutical compositions and dosage forms which comprise optically pure (-) sibutramine, optionally in combination with a phosphodiesterase inhibitor or a lipase inhibitor. Excerpt(s): This is a continuation-in-part of U.S. patent application 09/721,669, filed Nov. 27, 2000, which is a continuation of U.S. patent application 08/461,608, both of which are incorporated herein by reference in their entireties. This invention is directed to methods and compositions for the treatment or prevention of conditions using optically pure (-) sibutramine, optionally in combination with other pharmacologically active compounds. Sibutranmine, chemically named [N-1-[1-(4chlorophenyl)cyclobutyl]-- 3-methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (+)-bupropion Inventor(s): McCullough, John R.; (Hudson, MA), Rubin, Paul D.; (Sudbury, MA) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20010011103 Date filed: March 13, 2001 Abstract: Methods and compositions are disclosed utilizing the optically pure (+)-isomer of bupropion to assist in smoking cessation, for treating smoking and nicotine addiction, and for treating pain, including, but not limited to, chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders such as narcolepsy, chronic fatigue syndrome, fibromyalgia, seasonal affective disorder and premenstrual syndrome, while avoiding adverse affects associated with racemic bupropion. Excerpt(s): This invention relates to methods and pharmaceutical compositions for aiding smoking cessation, treating nicotine addiction, and pain, including chronic pain, neuropathetic pain and reflex sympathetic dystrophy, and other disorders. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and 1 are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except
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that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of using and compositions comprising sibutramine metabolites optionally in combination with other pharmacologically active compounds Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020010198 Date filed: January 29, 2001 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/662,135, filed Sep. 14, 2000, which is a continuation-in-part of U.S. application Ser. No. 09/372,158, filed Aug. 11, 1999, both of which are incorporated herein by reference in their entireties. The invention relates to methods of using and compositions comprising dopamine reuptake inhibitors such as racemic and optically pure metabolites of sibutramine, optionally in combination with other pharmacologically active compounds. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]3- -methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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MICROBIOLOGICALLY SOUND AND STABLE SOLUTIONS OF GAMMAHYDROXYBUTYRATE SALT FOR THE TREATMENT OF NARCOLEPSY Inventor(s): COOK, HARRY N.; (EDEN PRAIRIE, MN), DANIELSON, DOUG; (OTSEGO, MI), GODERSTAD, COLETTE; (ST. PAUL, MN), HAMILTON, MARTHA; (ST. PAUL, MN), REARDAN, DAYTON; (EXCELSIOR, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020077334 Date filed: December 22, 1999 Abstract: Disclosed are formulations of gamma-hydroxybutyrate in an aqueous medium that are resistant to microbial growth. Also disclosed are formulations of gammahydroxybutyrate that are also resistant to the conversion into GBL. Disclosed are methods to treat sleep disorders, including narcolepsy, with these stable formulations of GHB. The present invention also provides methods to treat alcohol and opiate withdrawal, reduced levels of growth hormone, increased intracranial pressure, and physical pain in a patient. Excerpt(s): This application claims priority from Provisional Application No. 60/113,745 filed Dec. 23, 1998, which is incorporated by reference herein. The present invention relates generally to the fields of pharmaceutical compositions to be used in treatments, such as, sleeping disorders, such as, e.g., narcolepsy (particularly cataplexy), drug abuse, alcohol and opiate withdrawal, a reduced level of growth hormone, anxiety, analgesia, effects in certain neurological disorders such as Parkinson's Disease, depression, certain endocrine disturbances and tissue protection following hypoxia/anoxia such as in stroke or myocardial infarction, or for an increased level of intracranial pressure or the like. The present invention particularly relates to the field of pharmaceutical production of microbiologically resistant and chemically stable preparations or solutions of gamma-hydroxybutyrate (GHB), also known as 4hydroxybutyrate, and the sodium salt of GHB (sodium oxybate) and other salts such as magnesium, ammonium and calcium, e.g. GHB is an endogenous compound with hypnotic properties that is found in many human body tissues. GHB is present, for example, in the mammalian brain and other tissues. In brain the highest GHB concentration is found in the hypothalamus and basal ganglia and GHB is postulated to function as a neurotransmitter (Snead and Morley, 1981). The neuropharmacologic effects of GHB include increases in brain acetylcholine, increases in brain dopamine, inhibition of GABA-ketoglutarate transaminase and depression of glucose utilization but not oxygen consumption in the brain. GHB is converted to succinate and then metabolized via the Krebs cycle. Clinical trials have shown that GHB increases delta sleep and improves the continuity of sleep (Ladinsky et al., 1983; Anden and Stock, 1973; Stock et al., 1973; Laborit, 1973; Lapierre et al., 1988; Lapierre et al., 1990; Yamda et al., 1967; Grove-White and Kelman, 1971; Scharf, 1985). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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PHARMACEUTICAL USES FOR NOS INHIBITORS Inventor(s): LOWE, JOHN A. III; (STONINGTON, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020151572 Date filed: August 11, 1999 Abstract: The present invention relates to new pharmaceutical uses for compounds that exhibit activity as nitric oxide synthase (NOS) inhibitors. Specifically, it relates to the use of NOS inhibitors, particularly selective neuronal NOS (N-NOS) inhibitors: (a) alone or in combination with another active agent for the treatment of psoriasis; (b) in combination with an antiinflammatory agent for the treatment of inflammatory disorders; (c) in combination with a narcotic analgesic (e.g., opiates such as morphine or demerol) for the treatment of pain; (d) alone or in combination with other active agents for the enhancement of cognition; and (e) alone or in combination with other active agents for the treatment of sleep disorders such as apnea, narcolepsy and insomnia. Excerpt(s): There are three known isoforms of NOS--an inducible form (I-NOS) and two constitutive forms referred to as, respectively, neuronal NOS (N-NOS) and endothelial NOS (E-NOS). Each of these enzymes carries out the conversion of arginine to citrulline while producing a molecule of nitric oxide (NO) in response to various stimuli. It is believed that excess nitric oxide (NO) production by NOS plays a role in the pathology of a number of disorders and conditions in mammals. For example, NO produced by INOS is thought to play a role in diseases that involve systemic hypotension such as toxic shock and therapy with certain cytokines. It has been shown that cancer patients treated with cytokines such as interleukin 1 (IL-1), interleukin 2 (IL-2) or tumor necrosis factor (TNF) suffer cytokine-induced shock and hypotension due to NO produced from macrophages, i.e., inducible NOS (I-NOS), see Chemical & Engineering News, December 20, p. 33, (1993). I-NOS inhibitors can reverse this. It is also believed that INOS plays a role in the pathology of diseases of the central nervous system such as ischemia. For example, inhibition of I-NOS has been shown to ameliorate cerebral ischemic damage in rats, see Am. J. Physiol., 268, p. R286 (1995)). Suppression of adjuvant induced arthritis by selective inhibition of I-NOS is reported in Eur. J. Pharmacol., 273, p. 15-24 (1995). NO produced by N-NOS is thought to play a role in diseases such as cerebral ischemia, pain, and opiate tolerance. For example, inhibition of N-NOS decreases infarct volume after proximal middle cerebral artery occlusion in the rat, see J. Cerebr. Blood Flow Metab., 14, p. 924-929 (1994). N-NOS inhibition has also been shown to be effective in antinociception, as evidenced by activity in the late phase of the formalin-induced hindpaw licking and acetic acid-induced abdominal constriction assays, see Br. J. Pharmacol., 110, p. 219-224 (1993). In addition, subcutaneous injection of Freund's adjuvant in the rat induces an increase in NOSpositive neurons in the spinal cord that is manifested in increased sensitivity to pain, which can be treated with NOS inhibitors, see Japanese Journal of Pharmacology, 75, p. 327-335 (1997). Finally, opioid withdrawal in rodents has been reported to be reduced by N-NOS inhibition, see Neuropsychopharmacol., 13, p. 269-293 (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmaceutically active morpholinol Inventor(s): Ascher, John A.; (Durham, NC), Bye, Alan; (Ware, GB), Joseph, Johnston Andrews; (Chapel Hill, NC), Susan, Learned-Coughlin Marie; (Durham, NC) Correspondence: David J Levy, Corporate Intellectual Property; Glaxosmithkline; Five Moore DR., PO Box 13398; Research Triangle Park; NC; 27709-3398; US Patent Application Number: 20030032643 Date filed: May 17, 2002 Abstract: Disclosed is the compound (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2- morpholinol and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions comprising them, and processes for their preparation; also disclosed is a method of treating depression, attention deficit hyperactivity disorder (ADHD), obesity, migraine, pain, sexual dysfunction, Parkinson's disease, Alzheimer's disease, addiction to cocaine or tobacco products, seasonal affective disorder, chronic fatigue, narcolepsy or cognitive impairment using such compound, salts, solvates or compositions. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/886,391 filed Jun. 22, 2001, which is a divisional application of U.S. Ser. No. 09/233,531, filed Jan. 20, 1999, now U.S. Pat. No. 6,274,579. This invention relates to an optically pure morpholinol, salts and solvates thereof, pharmaceutical formulations containing them and processes for their preparation and use. Bupropion is extensively metabolized in man as well as laboratory animals. Urinary and plasma metabolites include biotransformation products formed via hydroxylation of the tert-butyl group and/or reduction of the carbonyl group of bupropion. Four basic metabolites have been identified. They are the erythro- and threo-amino alcohols of bupropion, the erythroamino diol of bupropion, and a morpholinol metabolite. These metabolites of bupropion are pharmacologically active, but their potency and toxicity relative to bupropion have not been fully characterized. Because the plasma concentrations of the metabolites are higher than those of bupropion, they may be of clinical importance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Potassium channel blocking agents Inventor(s): Jensen, Bo Skaaning; (Copenhagen S, DK), Olesen, Soren Peter; (Klampenborg, DK), Peters, Dan; (Arlov, SE), Strobaek, Dorte; (Farum, DK), Teuber, Lene; (Vaerlose, DK) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20020049246 Date filed: December 29, 2000 Abstract: This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions.Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia,
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cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Excerpt(s): This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Ion channels are transmembrane proteins, which catalyze the transport of inorganic ions across cell membranes. The ion channels participate in processes as diverse as the generation and timing of action potentials, synaptic transmissions, secretion of hormones, contraction of muscles, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Salts of bicyclic, N-acylated imidazo-3-amines and imidazo-5-amines Inventor(s): Gerlach, Matthias; (Brachttal, DE), Sundermann, Corinna; (Aachen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030119842 Date filed: October 18, 2002 Abstract: Salts of a bicyclic, N-acylated imidazo-3-amine or an imidazo-5-amine of the formula: 1addition products thereof with acids, and methods for preparing the salts and addition products. Also disclosed are pharmaceutical compositions comprising the same and methods using the pharmaceutical compositions for the treatment or prophylaxis of pain, drug or alcohol abuse, diarrhoea, gastritis, ulcers, urinary incontinence, depression, narcolepsy, overweight, asthma, glaucoma, tinnitus, itching, hyperkinetic syndrome, epilepsy, or schizophrenia, for inducing anesthesia, and for anxiolysis. Excerpt(s): The present application is a continuation of international patent application no. PCT/EP01/03772, filed Apr. 3, 2001, designating the United States of America, and published in German as WO 01/81344, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. 100 19 714.0, filed Apr. 20, 2000. The present invention relates to salts of bicyclic, N-acylated imidazo-3-amines and imidazo-5-amines, to a process for producing them, to their use for producing pharmaceutical compositions and to pharmaceutical compositions containing these compounds. Individual compounds from the category of
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non-acylated bicyclic imidazo-3-amines and imidazo-5-amines which form the basis of the compounds according to the present invention are known to have interesting pharmacological properties. Thus, certain imidazo[1,2-a]pyridines are described as blood pressure-reducing active ingredients (GB-B-1,135,893), as anthelmintics and antimycotics (J. Med. Chem. 1972, 15, 982-985) and as anti-secretory active ingredients for the treatment of inflammatory diseases (EP-A-0 068 378). EP-A-0 266 890 and J. Med. Chem. 1987, 30, 2031-2046 also describe an effect of individual imidazopyridines against inflammatory diseases, in particular of the stomach. Further pharmacological effects described for individual representatives of the category of non-acylated imidazo-3amines and imidazo-5-amines are antibacterial properties (Chem. Pharm. Bull. 1992, 40, 1170), antiviral properties (J. Med. Chem. 1998, 41 5108-5112) and the effect as benzodiazepine-receptor antagonist (J. Heterocyclic Chem. 1998, 35, 1205-1217). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted pyrrole mannich bases to combat pain and allergic reactions Inventor(s): Gerlach, Matthias; (Brachttal, DE), Maul, Corinna; (Aachen, DE) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030023100 Date filed: June 25, 2002 Abstract: The invention relates to substituted pyrrole Mannich bases of general formula (I), wherein R.sup.1=H, a C.sub.1-10-alkyl-, aryl, a heteroaryl- or an aryl, heteroaryl-, CN, Br--, Cl or OH radical bound by a C.sub.1-6 alkylene group, R.sup.2=CH(R.sup.4)N(R.sup.5)(R.sup.6), R3, R3', R3" identically or individually represent H, F, Cl, Br, CF.sub.3, CN, NO.sub.2, SO.sub.2NH.sub.2, NHR', SR.sup.8, OR.sup.9, CO(OR.sup.10), CH.sup.2CO(OR.sup.11), COR.sup.15, a C.sub.1-10-alkyl-, aryl-, heteroaryl- aryl radical or a heteroalkyl radical bound by a C.sub.1-6 alkylene group, R.sup.4=an unsubstituted phenyl radical or a phenyl radical substituted at least with C.sub.1-4 alkyl, C.sub.1-3-alkoxy-, halogen-, a method for the production of the above-mentioned compounds, medicaments containing said compounds, and the use of said compounds in the production of medicaments. Said active ingredients are particularly suitable for pain therapy, and for treating inflammatory and allergic reactions, drug or alcohol abuse, diarrhoea, gastritis, ulcers, cardiovascular diseases, urinary incontinence, depressions, states of shock, migranes, narcolepsy, overweight, asthma, glaucoma, hyperkinetic syndrome, lack of drive, bulimia, anorexia, catalepsia, anxiolysis increasing vigilance and/or increasing libido. Excerpt(s): The invention relates to substituted pyrrole Mannich bases, processes for their preparation, medicaments comprising these compounds and the use of these compounds for the preparation of medicaments. Pain is one of the basic clinical symptoms. There is a worldwide need for effective pain treatments. The urgent need for action for target-orientated treatment of chronic and non-chronic states of pain appropriate for the patient, by which is to be understood successful and satisfactory pain treatment for the patient, is documented in the large number of scientific works which have been published in the field of applied analgesia and basic research in nociception in recent years. Conventional opioids, such as e.g. morphine, are effective in the treatment of severe to very severe pain. However, they have as undesirable concomitant symptoms, inter alia, respiratory depression, vomiting, sedation, constipation and development of tolerance.
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Treatment of convulsive states Inventor(s): Craig, Fiona; (Kent, GB), Davidson, Elizabeth Janina; (Herts, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030162810 Date filed: December 9, 2002 Abstract: Single enantiomer-threo-methylphenidate is useful in the therapy of a convulsant state, e.g. epilepsy, a bipolar disorder or narcolepsy. It may be administered topically. Excerpt(s): This invention relates to the treatment of epilepsy and other convulsive states, bipolar disorder and narcolepsy. Existing therapies for epilepsy have a variety of associated problems. For example, Epilim.RTM. (sodium valproate) is associated with liver dysfunction, including hepatic failure which has resulted in death, and has been found to interact with other drugs such as monoamine oxidase inhibitors. Drowsiness and sedation are among the side-effects on the CNS that have been noted for Epanutin.RTM. (phenytoin) and the benzodiazepine Valium.RTM. (diazepam). Drugs with the capacity to inhibit hepatic enzymes, such as cimetidine and omeprazole, have been found to reduce the clearance of benzodiazepines and can potentiate their action. A further issue with existing anti-epilepsy treatments is patient compliance. Most of the oral treatments require repeated dosing within the day and it is not uncommon for doses to be omitted in error or inadvertently for logistical reasons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of benzopyranols to treat neurological disorders Inventor(s): Evans, John Morris; (Roydon, GB), Parsons, Andrew; (Arlesey, GB), Thompson, Mervyn; (Harlow, GB), Upton, Neil; (Harlow, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020010209 Date filed: July 19, 2001 Abstract: Benzopyran derivatives and analogs are disclosed as useful for the treatment and/or prophylaxis of degenerative diseases such as Huntingdon's chorea, schizophrenia, neurological deficits associated with AIDS, sleep disorders (including circadian rhythm disorders, insomnia and narcolepsy), tics (e.g. Giles de la Tourette's syndrome), traumatic brain injury, tinnitus, neuralgia, especially trigeminal neuralgia, neuropathic pain, dental pain, cancer pain, inappropriate neuronal activity resulting in neurodysthesias in diseases such as diabetes, MS and motor neurone disease, ataxias, muscular rigidity (spasticity), temporomandibular joint dysfunction. Excerpt(s): This invention relates to a novel method of treatment. EP-A-0 126 311 discloses substituted benzopyran compounds having blood pressure lowering activity, including 6-acetyl-trans-4-(4-fluoroben- zoylamino)-3,4-dihydro-2,2-dimethyl-2H-1benzopyran-3-ol. Also EP-A-0 376 524, EP-A-0 205 292, EP-A-0 250 077, EP-A-0 093 535,
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EP-A-0 150 202, EP-A-0 076 075 and WO/89/05808 (Beecham Group plc) describe certain benzopyran derivatives which possess anti-hypertensive activity. 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 narcolepsy, 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 “narcolepsy” (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 narcolepsy. You can also use this procedure to view pending patent applications concerning narcolepsy. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON NARCOLEPSY Overview This chapter provides bibliographic book references relating to narcolepsy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on narcolepsy 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 “narcolepsy” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “narcolepsy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “narcolepsy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Commercial Perspectives: Sleep Disorders - Insomnia, Narcolepsy & Restless Leg Syndrome [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000UF8CU; http://www.amazon.com/exec/obidos/ASIN/B0000UF8CU/icongroupinterna
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Dave McKean - Narcolepsy: Retrospective Tentoonstelling; ISBN: 096420696X; http://www.amazon.com/exec/obidos/ASIN/096420696X/icongroupinterna
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Hla in Narcolepsy by Y. Honda, T. Juji (Editor) (1988); ISBN: 0387189564; http://www.amazon.com/exec/obidos/ASIN/0387189564/icongroupinterna
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Narcolepsy by C. Guilleminault (Editor); ISBN: 0883311615; http://www.amazon.com/exec/obidos/ASIN/0883311615/icongroupinterna
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Narcolepsy : A Scientific American article [DOWNLOAD: PDF] by Jerome M. Siegel (Author); ISBN: B00006BNPJ; http://www.amazon.com/exec/obidos/ASIN/B00006BNPJ/icongroupinterna
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Narcolepsy and Hypersomnia by Bedrich Roth, et al; ISBN: 380550490X; http://www.amazon.com/exec/obidos/ASIN/380550490X/icongroupinterna
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Narcolepsy: A Funny Disorder That's No Laughing Matter by Marguerite J. Utley; ISBN: 0964332809; http://www.amazon.com/exec/obidos/ASIN/0964332809/icongroupinterna
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Narcolepsy: Proceedings of the First International Symposium on Narcolepsy, July 1975, Montpellier, France by 1st, Montpellier, France, 1975. International Symposium on Narcolepsy, Christian Guilleminault; ISBN: 0470151242; http://www.amazon.com/exec/obidos/ASIN/0470151242/icongroupinterna
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Psychosocial Aspects of Narcolepsy by Meeta Goswami (Editor), et al (1996); ISBN: 0789060477; http://www.amazon.com/exec/obidos/ASIN/0789060477/icongroupinterna
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Sleep Disorders Sourcebook: Basic Consumer Health Information About Sleep and Its Disorders, Including Insomnia, Sleepwalking, Sleep Apmea, Restless Leg Syndrome, and Narcolepsy; by Jenifer Swanson (Editor), Jennifer Swanson (1999); ISBN: 0780802349; http://www.amazon.com/exec/obidos/ASIN/0780802349/icongroupinterna
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Sleep Disorders: Insomnia and Narcolepsy by Henry Kellerman; ISBN: 0876302649; http://www.amazon.com/exec/obidos/ASIN/0876302649/icongroupinterna
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The Official Patient's Sourcebook on Narcolepsy by James N. Parker (Editor), Philip M. Parker (Editor) (2002); ISBN: 0597831718; http://www.amazon.com/exec/obidos/ASIN/0597831718/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 “narcolepsy” (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:11 •
Narcolepsy. Author: Daniels, Luman Elmer.; Year: 1968; [Minneapolis] 1932
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Psychosocial aspects of narcolepsy Author: Goswami, Meeta.; Year: 2000; New York: Haworth Press, [c1992]; ISBN: 1560242221 http://www.amazon.com/exec/obidos/ASIN/1560242221/icongroupinterna
11
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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Chapters on Narcolepsy In order to find chapters that specifically relate to narcolepsy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and narcolepsy 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 “narcolepsy” (or synonyms) into the “For these words:” box.
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CHAPTER 8. MULTIMEDIA ON NARCOLEPSY Overview In this chapter, we show you how to keep current on multimedia sources of information on narcolepsy. 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 Narcolepsy 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 narcolepsy (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 narcolepsy: •
Narcolepsy [videorecording]. Year: 2000; Format: Videorecording; Boston, MA: Fanlight Productions, c2000
•
Narcolepsy, migraine headache [sound recording] Source: T. J. Murray; [made by] Sigma Information; Year: 1975; Format: Sound recording; Leonia, N.J.: Sigma, c1975
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CHAPTER 9. PERIODICALS AND NEWS ON NARCOLEPSY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover narcolepsy.
News Services and Press Releases One of the simplest ways of tracking press releases on narcolepsy 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 “narcolepsy” (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 narcolepsy. 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 “narcolepsy” (or synonyms). The following was recently listed in this archive for narcolepsy: •
Cephalon narcolepsy drug shows early promise to treat ADHD Source: Reuters Industry Breifing Date: May 20, 2003
•
Mylan files for FDA approval of generic narcolepsy drug Source: Reuters Industry Breifing Date: April 02, 2003
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•
More evidence of a link between narcolepsy and migraine Source: Reuters Medical News Date: March 31, 2003
•
Cephalon to seek expanded label for narcolepsy drug after positive study results Source: Reuters Industry Breifing Date: October 23, 2002
•
Cephalon narcolepsy drug approved in new markets Source: Reuters Industry Breifing Date: August 30, 2002
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Express Scripts to distribute Orphan Medical narcolepsy drug Source: Reuters Industry Breifing Date: August 23, 2002
•
FDA approves Xyrem for narcolepsy, as controlled substance Source: Reuters Medical News Date: July 18, 2002
•
FDA approves Orphan Medical's Xyrem for narcolepsy, but as "controlled substance" Source: Reuters Industry Breifing Date: July 18, 2002
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Narcolepsy education campaign launched in Germany Source: Reuters Medical News Date: July 10, 2002
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Panel backs Orphan Medical's Xyrem for narcolepsy Source: Reuters Industry Breifing Date: June 06, 2001
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FDA slates new advisory committee review date for narcolepsy drug candidate Source: Reuters Industry Breifing Date: April 11, 2001
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FDA postpones advisory review of Orphan Medical's narcolepsy drug Source: Reuters Industry Breifing Date: March 02, 2001
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Orphan Medical's narcolepsy NDA accepted by FDA; Canada approves Antizol Source: Reuters Industry Breifing Date: December 04, 2000
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Absence of neurotransmitter hypocretin linked to human narcolepsy Source: Reuters Industry Breifing Date: August 31, 2000
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Brain chemical deficiency linked to narcolepsy Source: Reuters Health eLine Date: August 29, 2000
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Narcolepsy drug helps relieve fatigue of multiple sclerosis Source: Reuters Health eLine Date: May 02, 2000
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Fatigue of MS relieved with narcolepsy drug Source: Reuters Medical News Date: May 02, 2000
Periodicals and News
•
Cephalon expands marketing territory for narcolepsy drug Source: Reuters Medical News Date: March 23, 2000
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New drug helps narcolepsy patients stay awake Source: Reuters Health eLine Date: March 14, 2000
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Modafinil improves excessive daytime sleepiness in narcolepsy Source: Reuters Medical News Date: March 14, 2000
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Orphan Medical narcolepsy drug demonstrates positive benefits Source: Reuters Medical News Date: January 20, 2000
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Underexpression of hypocretin 1 implicated in narcolepsy Source: Reuters Medical News Date: December 31, 1999
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Missing protein linked to narcolepsy Source: Reuters Health eLine Date: December 31, 1999
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Gene mutation associated with narcolepsy identified in dogs Source: Reuters Medical News Date: August 06, 1999
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Narcolepsy gene identified Source: Reuters Health eLine Date: August 05, 1999
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High rate of migraine observed in narcoleptic patients Source: Reuters Medical News Date: April 21, 1999
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FDA grants approval of first nonamphetamine for treatment of narcolepsy Source: Reuters Medical News Date: December 29, 1998
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FDA approves narcolepsy drug Source: Reuters Health eLine Date: December 28, 1998
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UK Medicines Control Agency Approves Modafinil For Narcolepsy Source: Reuters Medical News Date: March 04, 1998
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Narcolepsy Underdiagnosed In Older Patients Source: Reuters Medical News Date: February 26, 1998
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Narcolepsy Underdiagnosed In Over 40s Source: Reuters Health eLine Date: February 23, 1998
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Cephalon Submits NDA For Narcolepsy Drug Source: Reuters Medical News Date: January 01, 1997
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Cephalon To File For FDA Okay of Narcolepsy Drug By Year's End Source: Reuters Medical News Date: December 05, 1996
•
Effective Treatment For Narcolepsy Reported In Washington Source: Reuters Medical News Date: June 03, 1996
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[] - Cephalon Says Modafinil Effective In Patients With Narcolepsy Source: Reuters Medical News Date: March 15, 1996
•
[] - Cephalon Narcolepsy Drug Shows Promise Source: Reuters Medical News Date: February 13, 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. 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 “narcolepsy” (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 “narcolepsy” (or synonyms). If you know the name of a company that is relevant to narcolepsy, you can go to any stock trading Web site (such as http://www.etrade.com/) and
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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 “narcolepsy” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “narcolepsy” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on narcolepsy: •
Coping With Fatigue Source: Fibromyalgia Aware. p. 58-61. May-August 2002. Contact: Available from National Fibromyalgia Association. 2238 N. Glassell Street, Orange, CA 92865. (714) 921-0150. Summary: This newsletter article discusses fatigue in patients with fibromyalgia and medications that may help treat it. Fatigue is a common symptom in fibromyalgia. Fatigue can be related to other symptoms such as disrupted sleep and depression, or medical conditions like thyroid disorder or anemia. In addition to prescribing medication, patient education, exercise, social interaction, and psychological intervention are advised. One of the most encouraging drugs in the treatment of fatigue is modafanil (Provigil). This drug was originally used to alleviate sleepiness in patients with narcolepsy but has had positive results in patients with fibromyalgia and multiple sclerosis. Doctors often prescribe off-label medications (those medications FDA approved for other conditions) because no drugs have been approved by the FDA for fatigue. Doctors need to consider the side effects and benefits of any drug they prescribe. It is important to follow-up with the patient after six weeks on any medication. Side effects for drugs used for fatigue include anxiety, jitters, sleeplessness, headache, nausea, and rapid heart rate.
Academic Periodicals covering Narcolepsy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to narcolepsy. In addition to these sources, you can search for articles covering narcolepsy that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to
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http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. 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 narcolepsy. 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 narcolepsy. 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 narcolepsy: Amphetamines •
Systemic - U.S. Brands: Adderall; Desoxyn; Desoxyn Gradumet; Dexedrine; Dexedrine Spansule; DextroStat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202031.html
Antidepressants, Tricyclic •
Systemic - U.S. Brands: Anafranil; Asendin; Aventyl; Elavil; Endep; Norfranil; Norpramin; Pamelor; Sinequan; Surmontil; Tipramine; Tofranil; Tofranil-PM; Vivactil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202055.html
Fluoxetine •
Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html
Methylphenidate •
Systemic - U.S. Brands: Concerta; Ritalin; Ritalin-SR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202361.html
Modafinil •
Systemic - U.S. Brands: Provigil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203466.html
Pemoline •
Systemic - U.S. Brands: Cylert http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202444.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
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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 narcolepsy 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 “narcolepsy” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for narcolepsy: •
Modafinil (trade name: Provigil) http://www.rarediseases.org/nord/search/nodd_full?code=121
•
Gamma hydroxybutyrate http://www.rarediseases.org/nord/search/nodd_full?code=206
•
Oxbate (trade name: Xyrem) http://www.rarediseases.org/nord/search/nodd_full?code=1298
•
Gamma-hydroxybutyrate http://www.rarediseases.org/nord/search/nodd_full?code=715
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 Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
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
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
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
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
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
•
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.13 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:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
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
13
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). 14 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 Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “narcolepsy” (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 2148 32 928 0 1 3109
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “narcolepsy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
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 Biologists20 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.21 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.22 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 Narcolepsy In the following section, we will discuss databases and references which relate to the Genome Project and narcolepsy. 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).23 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. 20 Adapted 21
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. 22 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. 23 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 “narcolepsy” (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 narcolepsy: •
Cerebellar Ataxia, Deafness, and Narcolepsy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604121
•
Disseminated Sclerosis with Narcolepsy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?223300
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Narcolepsy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?161400
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Narcolepsy, Hla-associated Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605841 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
•
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
•
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 select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “narcolepsy” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 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 Database25 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 “narcolepsy” (or synonyms) into the search box, and
24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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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 narcolepsy 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 narcolepsy. 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 narcolepsy. 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 “narcolepsy”:
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Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Dizziness and Vertigo http://www.nlm.nih.gov/medlineplus/dizzinessandvertigo.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Seizures and Epilepsy http://www.nlm.nih.gov/medlineplus/tutorials/seizuresandepilepsyloader.html Sleep Apnea http://www.nlm.nih.gov/medlineplus/sleepapnea.html Sleep Disorders http://www.nlm.nih.gov/medlineplus/sleepdisorders.html Tuberous Sclerosis http://www.nlm.nih.gov/medlineplus/tuberoussclerosis.html
Within the health topic page dedicated to narcolepsy, the following was listed: •
General/Overviews How Well Are You Sleeping? Source: Food and Drug Administration http://www.fda.gov/fdac/features/2002/602_sleep.html Interactive Sleep Quiz Source: National Heart, Lung, and Blood Institute http://www.nhlbisupport.com/sleep_scripts/tfSleepQuiz.pl Sleep Disorders http://www.nlm.nih.gov/medlineplus/tutorials/sleepdisordersloader.html
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Treatment FDA Approves Xyrem for Cataplexy Attacks in Patients with Narcolepsy Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01157.html
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Alternative Therapy Melatonin Source: American Academy of Family Physicians http://familydoctor.org/258.xml Questions and Answers about Valerian for Insomnia and Other Sleep Disorders Source: National Institutes of Health, Office of Dietary Supplements http://ods.od.nih.gov/factsheets/valerian.html
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Coping Helping Yourself to a Good Night's Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/goodnights.cfm Living with Narcolepsy Source: National Sleep Foundation http://www.sleepfoundation.org/publications/livingnarcolepsy.cfm Tips for Shift Workers: How to Eat, Sleep and Stay Fit When You Work Nights Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01388
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Specific Conditions/Aspects Excessive Daytime Sleepiness Source: National Sleep Foundation http://www.sleepfoundation.org/epworth/quizfaq.cfm Hypersomnia Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/hypersomnia.htm Insomnia: How to Get a Good Night's Sleep Source: American Academy of Family Physicians http://familydoctor.org/110.xml Kleine-Levin Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/kleine_levin.htm Pain and Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/sleepandpain.cfm Public Split on Keeping Daylight Saving Time Year-Round Source: National Sleep Foundation http://www.sleepfoundation.org/PressArchives/yearround.cfm Sleep and the Traveler: How to Get the Most Out of Sleep When Traveling Source: National Sleep Foundation http://www.sleepfoundation.org/publications/travel.cfm Sleep Disorders (PDQ) Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/supportivecare/sleepdisorders/patient/ What Is Bruxism? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00337
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Children Nightmares and Night Terrors in Children Source: American Academy of Family Physicians http://familydoctor.org/566.xml
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Sleep Problems: Parasomnia Source: Nemours Foundation http://kidshealth.org/parent/general/sleep/parasomnia.html Sleepwalking in Children Source: American Academy of Family Physicians http://familydoctor.org/160.xml •
From the National Institutes of Health Brain Basics: Understanding Sleep Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/understanding_sleep_brain _basic_.htm Good Night's Sleep? Merely a Dream for Millions Source: National Institutes of Health http://www.nih.gov/news/WordonHealth/jun98/story02.htm Star Sleeper Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/sleep/starslp/
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Men Women & Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/women.cfm
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Organizations American Academy of Sleep Medicine http://www.aasmnet.org/ American Sleep Apnea Association http://www.sleepapnea.org/ National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/index.htm National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ National Sleep Foundation http://www.sleepfoundation.org/ Society for Neuroscience http://web.sfn.org/
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Research “Power Nap” Prevents Burnout; Morning Sleep Perfects a Skill Source: National Institute of Mental Health http://www.nih.gov/news/pr/jul2002/nimh-02.htm
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Scientists Pinpoint Possible Cause for Debilitating Sleep Disorder Narcolepsy Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/pressrelease_narcolepsy_082900.ht m?type=current •
Statistics 2000 Omnibus Sleep in America Poll Source: National Sleep Foundation http://www.sleepfoundation.org/publications/2000poll.cfm Events of 9-11 Took Their Toll on American's Sleep, Particularly for Women Source: National Sleep Foundation http://www.sleepfoundation.org/whatsnew/crisis_poll.cfm How Common Are Sleep Problems in Children? Source: Nemours Foundation http://kidshealth.org/research/sleep_problems.html
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Teenagers Pointers for Parents Source: National Sleep Foundation http://www.sleepfoundation.org/PressArchives/teens2.cfm Teens and Sleep Source: Nemours Foundation http://kidshealth.org/teen/your_body/take_care/sleep.html
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Women Women & Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/women.cfm
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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “narcolepsy” (or synonyms). The following was recently posted:
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Practice parameters for the treatment of narcolepsy: an update for 2000. Source: American Academy of Sleep Medicine - Professional Association; 1994 (updated 2001 Jun); 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2933&nbr=2159&a mp;string=narcolepsy Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Facts About Narcolepsy Summary: Narcolepsy is a chronic sleep disorder with no known cause. The main characteristic of narcolepsy is excessive and overwhelming daytime sleepiness, even after adequate nighttime sleep. Source: National Center on Sleep Disorders Research, National Heart, Lung, and Blood Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=715
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Narcolepsy Summary: A general overview of narcolepsy that includes a description of the disorder, and treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=783
•
Narcolepsy FAQs Summary: This document answers frequently asked questions about the cause, diagnosis, and treatment of narcolepsy. Source: Stanford Center for Narcolepsy http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7714
•
Test Your Sleep I.Q. Summary: This true-false quiz tests what you know about sleep. Questions cover topics on snoring, narcolepsy, insomnia, restless legs syndrome, and other issues. Source: National Center on Sleep Disorders Research, National Heart, Lung, and Blood Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2384
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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to narcolepsy. 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. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on narcolepsy can be purchased from NORD for a nominal fee. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Associations and Narcolepsy The following is a list of associations that provide information on and resources relating to narcolepsy: •
Narcolepsy Institute Telephone: (718) 920-6799 Toll-free: TTY: Fax: (718) 654-9580 Background: The Narcolepsy Institute is a not-for-profit, voluntary organization dedicated to providing comprehensive care to people with narcolepsy by integrating the medical, social, psychological, and spiritual dimensions of health in spirit of kindness and respect toward all, irrespective of race, creed, ethnicity, or social class. The
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Institute hopes that recipients of care may realize their optimal potential and live productively. Narcolepsy is a genetic disorder characterized by excessive daytime drowsiness. An individual with narcolepsy feels an irresistible urge to sleep during the day and often has disturbed nocturnal sleep as well. Established in 1985, the Institute strives to provide comprehensive psychosocial services and inform individuals about non-medical management of narcolepsy and improve the quality of their lives. The Narcolepsy Institute consists of 300 members. Educational materials include the biyearly newsletter 'Perspectives,' a guide entitled 'Narcolepsy Primer,' as well as an informational brochure 'Narcolepsy Institute.' Program activities include referrals, crisis intervention, counseling, nutritional planning, outreach, and advocacy. Relevant area(s) of interest: Narcolepsy •
Narcolepsy Network, Inc Telephone: (513) 891-3522 Fax: (513) 891-3836 Email:
[email protected] Web Site: http://www.narcolepsynetwork.org Background: The Narcolepsy Network is a national voluntary organization that was formed to serve the needs of people with narcolepsy. It is composed of people with narcolepsy, their families, friends, health care professionals, and other interested individuals. The Network is dedicated to improving the quality of life for people with narcolepsy and finding a cure for this disorder. To this end, the organization maintains a network of local support groups and chapters. The organization promotes programs of communication, advocacy, research, support, and education. A booklet entitled 'Narcolepsy: A Guide to Understanding' provides information on narcolepsy. Topics covered within the booklet include the symptoms, causes, diagnosis of the disorder, associated sleep apnea, treatments, and social implications. The organization also distributes a reading list, bibliography, and an educational materials order form. Relevant area(s) of interest: Narcolepsy
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to narcolepsy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with narcolepsy. 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 narcolepsy. 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.
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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 “narcolepsy” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “narcolepsy”. 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 “narcolepsy” (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 “narcolepsy” (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.26
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
26
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)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
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/
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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 narcolepsy: •
Basic Guidelines for Narcolepsy Narcolepsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000802.htm
•
Signs & Symptoms for Narcolepsy Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Hypersomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm
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Inability to speak Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Insomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Sleepiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Sleepy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Somnolence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Wakefulness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •
Diagnostics and Tests for Narcolepsy ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm EEG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003931.htm Polysomnogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm Polysomnography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm Sleep studies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm
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•
Background Topics for Narcolepsy Aggravated by Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002227.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Genetics Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Stimulants Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002308.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
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
163
NARCOLEPSY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] 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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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]
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Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] Allo: A female hormone. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] 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,
Dictionary 165
magnet therapy, spiritual healing, and meditation. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Alcohols: Compounds possessing both a hydroxyl (-OH) and an amino group (NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of
166 Narcolepsy
hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [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] Anthelmintics: Agents destructive to parasitic worms. They are used therapeutically in the treatment of helminthiasis in man and animal. [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody Specificity: The property of antibodies which enables them to react with some antigenic determinants and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site. [NIH]
Dictionary 167
Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] 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] Apathy: Lack of feeling or emotion; indifference. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Aqueous: Having to do with water. [NIH] Arecoline: An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetycholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH]
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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] 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] Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH]
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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] 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] 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] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [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] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH]
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Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH]
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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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] 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] Catalyse: To speed up a chemical reaction. [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] 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
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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] Causal: Pertaining to a cause; directed against a cause. [EU] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] 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] Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellopontine: Going from the cerebellum (the part of the brain responsible for coordinating movement) to the pons (part of the central nervous system located near the base of the brain.) [NIH] Cerebellopontine Angle: Junction between the cerebellum and the pons. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] 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]
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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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid
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secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [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] Claudication: Limping or lameness. [EU] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] 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] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup
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characteristics. [NIH] Colitis: Inflammation of the colon. [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] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH]
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Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] 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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm
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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] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a 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] 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] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [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] 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] Cyst: A sac or capsule filled with fluid. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, .
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New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] 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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusion: A false belief, not susceptible to argument or reason, and determined, pathologically, by some form of mental disorder. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple
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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] Dextrorotatory: Turning towards the right hand. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Diethylproprion: An appetite suppressant prescribed in the treatment of obesity. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diurnal: Occurring during the day. [EU]
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Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] 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] Down syndrome: A disorder caused by the presence of an extra chromosome 21 and characterized by mental retardation and distinguishing physical features. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [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] Dyskinesias: Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (movement disorders). Dyskinesias are also a relatively common manifestation of basal ganglia diseases. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU]
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Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] 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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles
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or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit.
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[NIH]
Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [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] 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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Faecal: Pertaining to or of the nature of feces. [EU]
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Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] 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] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Galanin: A neurotransmitter. [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] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
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Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [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 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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [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] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
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Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft vs Host Reaction: An immunological attack mounted by a graft against the host because of tissue incompatibility when immunologically competent cells are transplanted to an immunologically incompetent host; the resulting clinical picture is that of graft vs host disease. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Helminthiasis: Infestation with parasitic worms of the helminth class. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially
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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] 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] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] 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] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] 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,
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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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [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] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] 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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] 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
Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH]
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Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Inertia: Inactivity, inability to move spontaneously. [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]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH]
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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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [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]
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Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney 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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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]
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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] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
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] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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
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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] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
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]
Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannich Bases: Ketonic amines prepared from the condensation of a ketone with formaldehyde and ammonia or a primary or secondary amine. A Mannich base can act as the equivalent of an alpha,beta unsaturated ketone in synthesis or can be reduced to form physiologically active amino alcohols. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mazindol: Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but
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with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [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]
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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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Methyltransferase: A drug-metabolizing enzyme. [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] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [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] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] 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,
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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] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [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] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] 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]
Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] 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] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [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] 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]
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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] 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] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [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] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] 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] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] 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.
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Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [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] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by
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polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] 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] Nursing Care: Care given to patients by nursing service personnel. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] 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]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. [NIH] 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
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foreign literature it is often called osteoarthrosis deformans. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papilledema: Swelling around the optic disk. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasympathomimetic: 1. Producing effects resembling those of stimulation of the parasympathetic nerve supply to a part. 2. An agent that produces effects similar to those produced by stimulation of the parasympathetic nerves. Called also cholinergic. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU]
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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]
PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH]
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PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [NIH] 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] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [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]
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Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] 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] 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] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the
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mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Pontine: A brain region involved in the detection and processing of taste. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
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] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH]
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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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [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] 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] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [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] 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] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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]
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Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protriptyline: Tricyclic antidepressant similar in action and side effects to imipramine. It may produce excitation. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] 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] Psychotomimetic: Psychosis miming. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts.
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[NIH]
Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] 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] Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor antagonist. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [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 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative
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risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [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]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] 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]
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Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] Schizophrenia, Catatonic: A type of schizophrenia characterized by abnormality of motor behavior which may involve particular forms of stupor, rigidity, excitement or inappropriate posture. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH]
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Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
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Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [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 apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [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] Sleep Paralysis: A state experienced by a person while going to sleep or on waking: consciousness is present but muscular movement is lost as well as the ability to speak. [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]
Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH]
Social Class: A stratum of people with similar position and prestige; includes social stratification. Social class is measured by criteria such as education, occupation, and income.
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[NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Sodium Oxybate: The sodium salt of 4-hydroxybutyric acid. Anesthetic used for both induction and maintenance. It may cause bradycardia and dyskinesias. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] 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] 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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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] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] 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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Subthalamus: A transition zone in the anterior part of the diencephalon interposed between the thalamus, hypothalamus, and tegmentum of the mesencephalon. Components of the subthalamus include the subthalamic nucleus, zona incerta, nucleus of field H, and the
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nucleus of ansa lenticularis. The latter contains the entopeduncular nucleus. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [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] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of 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] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU]
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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] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] 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] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are
Dictionary 217
concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of 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] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [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] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] 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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]
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]
218 Narcolepsy
Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transplantation Immunology: A general term for the complex phenomena involved in alloand xenograft rejection by a host and graft vs host reaction. Although the reactions involved in transplantation immunology are primarily thymus-dependent phenomena of cellular immunity, humoral factors also play a part in late rejection. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH]
Dictionary 219
Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [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] 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] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Vertebrae: A bony unit of the segmented spinal column. [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] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH]
220 Narcolepsy
Vibrio cholerae: The etiologic agent of cholera. [NIH] Villous: Of a surface, covered with villi. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]
Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
221
INDEX A Abdominal, 108, 163, 191, 201, 205 Abdominal Pain, 163, 191 Ablate, 13, 163 Ablation, 50, 163 Acceptor, 163, 201, 217 Acetylcholine, 13, 107, 163, 173, 199 Action Potentials, 98, 110, 163 Adaptation, 163, 190 Adenylate Cyclase, 163, 173 Adipocytes, 163, 191 Adjuvant, 108, 163 Adolescence, 11, 101, 103, 163, 202 Adrenal Cortex, 163, 177 Adrenal Medulla, 100, 163, 171, 182, 199 Adrenergic, 18, 28, 64, 80, 101, 106, 163, 167, 180, 182, 203, 205, 206, 215, 218, 220 Adverse Effect, 163, 212 Afferent, 8, 164, 191, 200, 203, 211 Affinity, 30, 99, 164, 168, 178, 198, 213 Age of Onset, 15, 34, 164 Agonist, 17, 20, 31, 164, 167, 170, 180, 188, 196, 197, 199, 203 Airway, 164, 212 Alertness, 12, 30, 31, 32, 164, 172 Algorithms, 164, 169 Alkaline, 164, 165, 171 Alkaloid, 164, 167, 170, 174, 196, 199, 220 Alleles, 13, 20, 21, 33, 104, 164, 192 Allo, 164, 218 Allografts, 164, 187 Allylamine, 164, 165 Alpha Particles, 164, 208 Alpha-1, 164, 205 Alternative medicine, 124, 164 Amenorrhea, 165, 170 Amine, 9, 110, 165, 187, 193 Amino Acid Sequence, 165, 166, 169, 183, 185 Amino Acids, 165, 169, 185, 199, 202, 204, 206 Amino Alcohols, 109, 165, 193 Ammonia, 165, 193 Amphetamine, 9, 12, 28, 58, 86, 99, 165, 178, 193 Amplification, 20, 165 Amygdala, 6, 32, 165, 169, 192, 211, 216 Anaesthesia, 165, 189
Anal, 165, 182 Analgesic, 108, 165, 174, 192, 196, 200 Analog, 80, 165 Anaphylatoxins, 165, 175 Anatomical, 22, 28, 31, 35, 165, 189, 210 Anemia, 125, 139, 165 Anesthesia, 39, 101, 110, 164, 166, 177 Anesthetics, 166, 168, 182 Angina, 98, 110, 166, 206 Angina Pectoris, 98, 110, 166, 206 Animal model, 7, 9, 16, 28, 57, 166 Anions, 166, 191 Anorexia, 111, 166 Anoxia, 107, 166 Antagonism, 36, 166 Anthelmintics, 111, 166 Anthropometry, 24, 25, 26, 27, 166 Antibacterial, 111, 166, 213 Antibiotic, 166, 202, 213 Antibodies, 16, 71, 166, 183, 186, 188, 189, 193, 196, 204 Antibody, 16, 164, 166, 167, 175, 182, 186, 187, 188, 189, 194, 196, 211, 213 Antibody Specificity, 16, 166 Anticoagulant, 167, 206 Anticonvulsants, 167, 168 Antidepressant, 167, 170, 184, 188, 207 Antigen, 7, 51, 104, 164, 166, 167, 175, 187, 188, 189, 194, 211 Antigen-Antibody Complex, 167, 175 Antipsychotic, 167, 208 Antiseptic, 167, 171 Antiviral, 111, 167, 202 Anxiety, 8, 32, 70, 71, 74, 98, 105, 106, 107, 110, 125, 167, 201, 206, 210 Anxiety Disorders, 32, 71, 74, 167 Apathy, 101, 167 Aqueous, 107, 167, 169, 178, 181 Arecoline, 82, 167 Arginine, 108, 165, 167, 199 Aromatic, 167, 203 Arrhythmia, 98, 110, 167 Arterial, 164, 168, 188, 206, 215 Arteries, 168, 170, 172, 177, 195, 197 Arteriovenous, 62, 168 Articular, 168, 200 Assay, 5, 15, 23, 168 Astringent, 168, 171
222 Narcolepsy
Astrocytes, 168, 185, 196, 198 Asymptomatic, 52, 81, 168 Ataxia, 138, 139, 168, 188, 216 Atrophy, 138, 139, 168 Atypical, 70, 101, 168 Auditory, 6, 32, 58, 101, 168 Autoimmune disease, 168, 196 Autonomic, 40, 77, 163, 167, 168, 199, 202 Autopsy, 5, 168 Autoradiography, 64, 168 Avian, 18, 168 Axons, 15, 168, 200, 205 B Bacteria, 12, 166, 167, 168, 176, 182, 184, 195, 213, 217, 219 Barbiturates, 103, 168, 210 Basal Ganglia, 107, 167, 168, 169, 173, 180, 192, 200 Basal Ganglia Diseases, 168, 169, 173, 180 Base, 17, 169, 172, 178, 185, 191, 193, 216 Benign, 169, 186, 198 Benzene, 169 Benzodiazepines, 103, 112, 169 Beta-Endorphin, 54, 169 Bile, 169, 184, 192, 214 Biochemical, 9, 12, 19, 20, 164, 169, 200, 211 Biosynthesis, 99, 100, 169 Biotechnology, 36, 116, 124, 135, 137, 138, 139, 140, 169 Biotransformation, 109, 169 Bipolar Disorder, 63, 112, 144, 169 Bladder, 98, 109, 110, 169, 184, 189, 196, 206, 218, 219 Blastocyst, 169, 176 Bloating, 170, 191 Blood Coagulation, 170, 171, 216 Blood Platelets, 170, 211 Blood pressure, 14, 111, 112, 170, 171, 188, 196, 212, 213 Blood vessel, 170, 171, 173, 174, 182, 191, 202, 212, 214, 216, 219 Blood-Brain Barrier, 101, 170, 192 Body Composition, 24, 25, 26, 27, 170 Body Fluids, 170, 213 Body Mass Index, 170, 201 Bone Density, 24, 25, 26, 27, 170 Bowel, 165, 170, 179, 190, 214 Bowel Movement, 170, 179, 214 Bradycardia, 170, 213 Bradykinin, 170, 199 Brain Stem, 47, 170, 172
Branch, 157, 170, 199, 201, 213, 215, 216 Bromocriptine, 46, 80, 170 Bronchitis, 170, 173 Bulimia, 111, 170 Bupropion, 70, 99, 100, 105, 109, 170 C Calcium, 13, 35, 107, 171, 175, 212 Calmodulin, 13, 171 Capsules, 171, 180 Carbohydrate, 171, 204, 210, 211 Carbon Dioxide, 171, 178, 184, 209 Carcinogenic, 169, 171, 206, 214 Carcinogens, 171, 200 Cardiac, 164, 171, 182, 183, 197, 214 Cardioselective, 171, 206 Cardiovascular, 6, 18, 111, 165, 171, 211 Cardiovascular disease, 18, 111, 171 Case report, 40, 48, 57, 68, 171, 174 Case series, 52, 171, 174 Catalyse, 171, 217 Catechol, 72, 82, 171 Catecholamine, 171, 180, 203 Cations, 171, 191 Caudal, 36, 171, 179, 188, 200, 205 Caudate Nucleus, 169, 172, 200 Causal, 7, 172, 182 Celiac Disease, 35, 172 Cell Differentiation, 172, 212 Cell Division, 138, 168, 172, 194, 204, 206, 210 Cell membrane, 98, 110, 172, 178, 183, 184, 203, 205, 213 Cell proliferation, 172, 190, 212 Cell Respiration, 172, 209 Central Nervous System Infections, 172, 186 Central Nervous System Stimulants, 70, 172 Cerebellar, 138, 168, 172, 208 Cerebellopontine, 42, 172 Cerebellopontine Angle, 42, 172 Cerebellum, 172, 184, 205, 208 Cerebral, 98, 105, 106, 108, 110, 168, 170, 172, 173, 176, 182, 183, 184, 186, 195, 213, 216 Cerebral Arteries, 172, 195 Cerebral hemispheres, 168, 170, 172, 173, 216 Cerebrospinal, 5, 8, 15, 54, 59, 75, 172, 173, 212 Cerebrospinal fluid, 5, 8, 15, 54, 59, 75, 173, 212
Index 223
Cerebrovascular, 169, 171, 173, 216 Cerebrum, 172, 173, 204, 216, 218 Cervix, 173, 184 Character, 166, 173, 178, 185 Chemotactic Factors, 173, 175 Cholera, 13, 173, 219, 220 Cholera Toxin, 13, 173 Cholinergic, 6, 8, 18, 20, 22, 23, 28, 35, 52, 61, 80, 81, 87, 102, 167, 173, 199, 201, 211 Chorea, 112, 167, 173 Choreatic Disorders, 173 Chromosomal, 165, 173 Chromosome, 7, 21, 27, 58, 173, 176, 180, 192, 210 Chronic Disease, 15, 173 Chronic Fatigue Syndrome, 42, 100, 105, 173 Chronic Obstructive Pulmonary Disease, 98, 109, 110, 173 Chronic renal, 173, 204 Cimetidine, 112, 173 Circadian, 8, 9, 13, 41, 55, 86, 112, 174 Circadian Rhythm, 9, 112, 174 Circulatory system, 174, 181, 190 Claudication, 98, 110, 174 Clear cell carcinoma, 174, 178 Clinical Medicine, 174, 205 Clinical study, 174, 176 Clinical trial, 3, 14, 93, 95, 107, 135, 174, 176, 196, 202, 207, 208 Cloning, 7, 169, 174 Coca, 174 Cocaine, 4, 99, 105, 106, 109, 174, 194 Cochlear, 174, 217, 219 Cochlear Diseases, 174, 217 Codeine, 46, 174, 200 Cofactor, 174, 206, 216 Cognition, 46, 108, 174 Cohort Studies, 174, 182 Colitis, 175, 191 Collapse, 101, 175, 212 Colloidal, 175, 181 Complement, 19, 165, 175, 185, 193 Complementary and alternative medicine, 85, 90, 175 Complementary medicine, 85, 175 Complete remission, 42, 175, 209 Computational Biology, 135, 137, 175 Computed tomography, 24, 25, 26, 27, 170, 175, 176 Computerized axial tomography, 175, 176 Computerized tomography, 175, 176
Conception, 11, 176 Concomitant, 32, 91, 111, 176 Cones, 176, 203, 209 Conjugated, 16, 176, 177 Conjugation, 169, 176 Conjunctiva, 176, 218 Connective Tissue, 176, 184, 209, 215 Consciousness, 46, 102, 165, 176, 178, 179, 212 Constipation, 111, 167, 176, 191, 212 Constriction, 108, 176, 191, 207 Consumption, 18, 104, 176, 201 Contraindications, ii, 176 Controlled clinical trial, 29, 176 Controlled study, 49, 81, 176 Convulsions, 98, 109, 110, 176 Convulsive, 112, 176 Coordination, 10, 31, 172, 177, 196 Coronary, 98, 101, 109, 110, 166, 171, 177, 195, 197 Coronary Circulation, 166, 177 Coronary heart disease, 171, 177 Coronary Thrombosis, 177, 195, 197 Cortex, 168, 172, 177, 183, 187, 195, 208 Cortical, 13, 17, 68, 177, 183, 211, 216 Cortisol, 69, 177 Cranial, 172, 177, 186, 190, 198, 200, 202, 218, 219 Craniocerebral Trauma, 169, 177, 186, 216, 217 Cross-Sectional Studies, 177, 182 Curare, 177, 196 Curative, 177, 216 Cyclic, 14, 163, 171, 177, 186, 199, 203, 210 Cyst, 42, 177 Cytochrome, 174, 177 Cytokine, 108, 178 Cytoplasm, 172, 173, 178, 186 Cytotoxic, 178, 189, 212 D Databases, Bibliographic, 135, 178 Deamination, 178, 196 Decarboxylation, 178, 187, 196 Degenerative, 15, 112, 178, 185, 200 Dehydration, 173, 178 Deletion, 37, 178 Delusion, 101, 178 Dementia, 98, 110, 167, 178 Dendrites, 178, 198 Dendritic, 13, 178, 194 Density, 21, 25, 26, 27, 56, 170, 178, 200 Depolarization, 178, 212
224 Narcolepsy
DES, 81, 102, 165, 178 Desipramine, 99, 100, 178 Dextroamphetamine, 165, 178, 195 Dextrorotatory, 100, 105, 179 Diagnostic procedure, 97, 124, 179 Dialyzer, 179, 186 Diarrhea, 179, 191 Diarrhoea, 98, 109, 110, 111, 179 Diastolic, 179, 188 Diencephalon, 62, 179, 182, 188, 206, 214, 216 Dietary Fats, 179, 192 Diethylproprion, 100, 179 Digestion, 169, 170, 179, 190, 192, 214, 219 Digestive system, 95, 179 Dimethyl, 105, 106, 112, 179 Diphtheria, 13, 179 Diphtheria Toxin, 13, 179 Direct, iii, 4, 7, 33, 127, 172, 174, 179, 180, 203, 208, 215 Dissection, 7, 179 Dissociation, 164, 179 Distal, 179, 205, 207 Diurnal, 32, 65, 179 Dizziness, 63, 144, 180 Dopa, 46, 57, 80, 82, 180, 192 Dorsal, 21, 24, 31, 180, 182, 205, 211 Dorsum, 180 Dosage Forms, 105, 106, 180 Dose-dependent, 22, 180 Down syndrome, 63, 180 Drive, ii, vi, 79, 81, 111, 180, 192 Drug Interactions, 128, 129, 180 Drug Tolerance, 180, 217 Duodenum, 169, 180, 214 Dyskinesias, 169, 180, 213 Dysmenorrhea, 98, 110, 180 Dysplasia, 139, 180 Dystrophy, 100, 105, 138, 180 E Eating Disorders, 4, 105, 106, 181 Effector, 163, 175, 181, 198, 199, 203 Effector cell, 181, 198, 199 Efficacy, 19, 47, 69, 80, 82, 93, 181 Elective, 181 Electrolyte, 181, 205, 213 Electrons, 169, 181, 191, 201, 208 Electrophoresis, 20, 181 Electroplating, 171, 181 Embryo, 169, 172, 181, 189 Emphysema, 173, 181 Emulsion, 168, 181
Encephalitis, 65, 181 Encephalitis, Viral, 181 Endemic, 173, 181, 214 Endocrine System, 181, 198 Endocytosis, 20, 181 Endothelial cell, 170, 182, 216 Endothelium, 182, 199 Endothelium-derived, 182, 199 Endotoxin, 182, 218 End-stage renal, 173, 182, 204 Energy balance, 182, 191 Enkephalin, 169, 182 Environmental Exposure, 11, 182, 200 Environmental Health, 134, 136, 182 Enzymatic, 99, 100, 171, 175, 182, 187, 209 Enzyme, 23, 163, 181, 182, 186, 192, 195, 196, 202, 203, 206, 212, 216, 220 Epidemic, 14, 182, 214 Epidemiologic Studies, 11, 182 Epidemiological, 7, 74, 182 Epinephrine, 163, 180, 182, 199, 218 Epithalamus, 179, 182, 192 Epithelial, 173, 182 Epithelial Cells, 173, 182 Epitope, 16, 182, 183 Epitope Mapping, 16, 183 Ergot, 170, 183 Erythrocytes, 165, 183 Esophagus, 179, 183, 214 Essential Tremor, 139, 183 Ethnic Groups, 41, 42, 53, 183 Eukaryotic Cells, 183, 189 Euphoria, 101, 183 Evacuation, 176, 183 Evoke, 183, 214 Excitability, 35, 183, 197 Excitation, 22, 34, 172, 183, 207 Excitatory, 9, 13, 24, 34, 35, 183, 185, 188 Exhaustion, 166, 183 Exocytosis, 100, 183 Exogenous, 6, 169, 183 Exon, 37, 183 Expiration, 183, 209 Extensor, 183, 207 Extracellular, 14, 23, 99, 168, 176, 181, 183, 195, 198, 213 Extracellular Space, 183, 195 Extrapyramidal, 167, 180, 183 Eye Movements, 12, 183 F Faecal, 179, 183 Family Planning, 135, 184
Index 225
Fat, 24, 25, 26, 27, 163, 170, 177, 184, 191, 192, 196, 201, 209 Fatigue, 11, 109, 122, 125, 173, 184, 186, 202 Feces, 176, 183, 184, 214 Fibrosis, 98, 109, 110, 139, 164, 184, 210 Flexion, 27, 184 Fluoxetine, 38, 128, 184 Fold, 4, 184 Forearm, 170, 184 Fourth Ventricle, 184, 193, 216 Fundus, 184 G Galanin, 4, 184 Gallbladder, 163, 179, 184 Gamma-hydroxybutyrate, 10, 30, 47, 80, 81, 101, 107, 129, 184 Ganglia, 163, 169, 184, 198, 202 Ganglioside, 71, 184 Gap Junctions, 184, 215 Gas, 165, 171, 184, 188, 191, 199, 209 Gas exchange, 184, 209 Gastric, 14, 173, 180, 184, 187, 202 Gastric Acid, 173, 184 Gastrin, 174, 184, 187 Gastritis, 110, 111, 185 Gastrointestinal, 98, 109, 110, 170, 182, 185, 211, 213, 214, 219 Gastrointestinal tract, 185, 211, 213 Gels, 20, 185 Gene Expression, 12, 139, 185 Gene Library, 185 Genetic Code, 185, 200 Genetic Engineering, 169, 174, 185 Genetics, 9, 27, 34, 42, 51, 73, 161, 176, 185, 202 Genomic Library, 7, 185 Genotype, 28, 164, 185, 203 Germ Cells, 185, 194, 213, 216 Gland, 163, 185, 201, 206, 210, 214, 216, 217 Gliosis, 65, 185 Glucose, 15, 107, 138, 185, 186, 190 Glutamate, 6, 15, 17, 185 Gluten, 19, 172, 185 Glycoprotein, 185, 216, 218 Governing Board, 185, 205 Gp120, 185, 202 Graft, 164, 186, 187, 218 Graft vs Host Reaction, 186, 218 Granulocytes, 186, 191, 212, 220
Growth, 101, 107, 138, 163, 166, 167, 172, 186, 190, 193, 198, 200, 204, 210, 213, 216, 217, 218 Guanylate Cyclase, 186, 199 Gyrus Cinguli, 186, 192 H Hallucination, 101, 186 Haplotypes, 21, 52, 186 Haptens, 164, 186 Headache, 48, 119, 125, 186, 205, 212 Headache Disorders, 186 Heart attack, 171, 186 Heart failure, 186, 205 Helminthiasis, 166, 172, 186 Hemodialysis, 46, 179, 186 Hemoglobin, 166, 183, 186, 187, 191 Hemoglobinuria, 138, 187 Hemorrhage, 177, 186, 187, 214 Hemostasis, 187, 211 Hepatic, 112, 187, 196 Hereditary, 9, 16, 173, 187, 209 Heredity, 51, 65, 185, 187 Heterogeneity, 50, 164, 187 Heterogenic, 187 Heterogenous, 32, 187 Hippocampus, 187, 192, 211 Histamine, 17, 165, 167, 173, 187 Histocompatibility, 19, 53, 59, 187 Holidays, 19, 187 Homeostasis, 6, 15, 53, 59, 187 Homologous, 164, 187, 210, 215 Hormonal, 168, 187 Hormone, 15, 80, 101, 107, 164, 169, 174, 177, 178, 182, 184, 187, 191, 206, 209, 210, 212, 213, 216, 217 Host, 164, 186, 187, 218, 220 Human Development, 27, 134, 187 Humoral, 187, 218 Hybrid, 20, 187 Hydrogen, 163, 165, 169, 171, 187, 188, 195, 199, 201, 203, 207 Hydrolysis, 169, 188, 203, 204, 206 Hydroxylation, 100, 109, 188 Hypersensitivity, 188, 209 Hypertension, 98, 101, 110, 171, 188, 190, 205, 206 Hyperthyroidism, 188, 206 Hypertrophy, 188, 205 Hypnotic, 13, 85, 107, 188 Hypotension, 108, 167, 176, 188 Hypothalamic, 5, 12, 14, 17, 23, 36, 188 Hypoxia, 107, 188, 216
226 Narcolepsy
I Ibotenic Acid, 188, 196 Id, 83, 89, 145, 148, 149, 156, 158, 188 Idiopathic, 43, 47, 54, 56, 67, 188 Imipramine, 188, 207 Immune function, 188, 189 Immune response, 163, 167, 168, 186, 188, 193, 214 Immune system, 181, 188, 189, 193, 196, 219, 220 Immunity, 62, 188, 218 Immunochemistry, 183, 188 Immunodeficiency, 138, 188 Immunofluorescence, 16, 188 Immunoglobulin, 36, 166, 189, 196 Immunohistochemistry, 20, 189 Immunology, 37, 55, 102, 163, 164, 189, 218 Immunosuppressive, 102, 189 Immunosuppressive Agents, 102, 189 Impairment, 12, 91, 109, 168, 189, 194, 207 Implantation, 176, 189 Impotence, 189, 220 In situ, 12, 189 In Situ Hybridization, 12, 189 In vitro, 17, 28, 55, 189, 211 In vivo, 15, 17, 28, 33, 34, 45, 55, 101, 189, 195 Incision, 189, 190 Incontinence, 98, 105, 106, 109, 110, 111, 189 Indicative, 115, 189, 201, 219 Induction, 52, 81, 101, 167, 189, 206, 213 Inertia, 43, 189 Infarction, 189 Infection, 168, 173, 179, 181, 188, 189, 193, 198, 202, 209, 214, 220 Infertility, 170, 189 Inflammation, 4, 170, 175, 181, 184, 185, 190, 197, 209, 214, 215, 217 Infusion, 10, 82, 190 Inorganic, 98, 110, 190, 196 Inositol, 20, 190, 210 Inotropic, 180, 190 Insight, 35, 190 Institutionalization, 15, 190 Insulator, 190, 196 Interleukins, 189, 190 Intermittent, 35, 98, 110, 190 Interpersonal Relations, 19, 190 Intestinal, 172, 173, 190, 193 Intestine, 170, 190, 191
Intoxication, 88, 190, 220 Intracellular, 13, 35, 189, 190, 199, 205, 208, 210, 212 Intracranial Hypertension, 186, 190, 217 Intracranial Pressure, 107, 190, 207 Intravenous, 101, 190 Intrinsic, 164, 190 Introns, 185, 190 Invasive, 8, 29, 188, 190, 193 Involuntary, 169, 173, 180, 183, 190, 197, 208, 213 Ion Channels, 98, 110, 168, 191, 198, 199, 215 Ionizing, 164, 182, 191, 193 Ions, 98, 110, 169, 171, 179, 181, 188, 191, 195, 205, 213 Irritable Bowel Syndrome, 98, 105, 106, 109, 110, 191 Ischemia, 101, 108, 168, 184, 191 J Jealousy, 38, 191 Joint, 34, 112, 168, 191, 200, 215 K Kb, 134, 191 Keto, 191, 217 Kidney Disease, 95, 98, 109, 110, 134, 139, 191 Kinetics, 14, 191 L Labile, 175, 191 Large Intestine, 179, 190, 191, 208, 212 Latency, 29, 33, 43, 58, 61, 72, 76, 77, 191 Latent, 191, 205 Leptin, 68, 191 Lesion, 5, 185, 191, 192 Lethal, 103, 179, 191 Leucine, 169, 191, 202 Leucocyte, 51, 164, 191 Leukemia, 138, 192 Leukocytes, 173, 186, 190, 192, 218 Levo, 58, 180, 192 Levodopa, 180, 192, 211 Libido, 111, 192 Library Services, 156, 192 Ligament, 192, 206 Ligands, 4, 20, 192 Limbic, 32, 65, 165, 186, 192 Limbic System, 32, 165, 186, 192 Linkage, 7, 21, 34, 36, 58, 192 Linkage Disequilibrium, 34, 192 Lipase, 105, 192 Lipid, 191, 192, 196
Index 227
Liver, 101, 112, 163, 169, 179, 181, 184, 187, 192, 196 Localization, 189, 192 Localized, 8, 179, 189, 192, 196, 204 Locomotion, 8, 192, 193, 204 Locomotor, 30, 193 Locus Coeruleus, 15, 18, 22, 24, 193 Lupus, 193, 215 Lymphocyte, 167, 193, 194 Lymphoid, 166, 191, 193 Lymphoma, 138, 193 M Magnetic Resonance Imaging, 86, 193 Major Histocompatibility Complex, 104, 186, 193 Malabsorption, 138, 172, 193 Malformation, 62, 193 Malignant, 138, 193, 198 Malnutrition, 168, 193, 197 Manic, 167, 169, 193, 207 Manic-depressive psychosis, 193, 207 Manifest, 27, 193 Man-made, 171, 193 Mannich Bases, 111, 193 Mastication, 193, 218 Mazindol, 55, 60, 193 Mediate, 14, 28, 180, 194 Mediator, 180, 194, 211 MEDLINE, 135, 137, 139, 194 Meiosis, 194, 215 Melanin, 193, 194, 203, 218 Melanocytes, 194 Melanoma, 138, 194 Membrane Glycoproteins, 194 Memory, 98, 110, 166, 178, 194 Meninges, 172, 177, 194 Menopause, 194, 206 Menstrual Cycle, 194, 205 Menstruation, 165, 180, 194, 205 Mental Disorders, 95, 194, 207 Mental Retardation, 140, 180, 194 Mesencephalic, 193, 194, 208 Meta-Analysis, 51, 194 Metabolite, 106, 109, 169, 179, 194 Methamphetamine, 76, 195 Methionine, 169, 179, 195 Methylphenidate, 90, 99, 112, 128, 195 Methyltransferase, 72, 82, 195 MI, 107, 161, 195 Microbe, 195, 217 Microbiology, 163, 168, 195 Microdialysis, 15, 23, 28, 31, 195
Microorganism, 174, 195, 220 Middle Cerebral Artery, 108, 195 Milliliter, 170, 195 Mitochondrial Swelling, 195, 197 Modeling, 9, 195 Modification, 185, 195, 208 Modulator, 17, 195 Molecular Structure, 166, 195, 218 Monitor, 5, 195, 199 Monoamine, 39, 60, 61, 99, 105, 106, 112, 165, 179, 196, 211, 218 Monoamine Oxidase, 39, 112, 165, 179, 196, 211, 218 Monoclonal, 20, 196 Monoclonal antibodies, 20, 196 Mononuclear, 196, 218 Morphine, 108, 111, 174, 196, 197, 200 Motility, 196, 211 Motion Sickness, 196, 197 Motor Activity, 15, 34, 41, 86, 176, 196 Motor nerve, 196 Mucosa, 172, 193, 196, 206 Mucus, 196, 210 Multicenter study, 19, 196 Multiple sclerosis, 48, 61, 67, 71, 122, 125, 196 Muscimol, 31, 196 Muscle Fibers, 196, 197 Muscle relaxant, 103, 196 Muscle tension, 196, 197 Muscular Atrophy, 138, 197 Muscular Dystrophies, 180, 197 Mydriatic, 197, 220 Myelin, 196, 197, 198 Myocardial infarction, 101, 107, 177, 195, 197, 206 Myocardial Ischemia, 166, 197 Myocarditis, 179, 197 Myocardium, 166, 195, 197 Myotonic Dystrophy, 138, 197 N Naloxone, 54, 82, 169, 197 Narcosis, 197 Narcotic, 108, 196, 197 Nausea, 125, 167, 180, 197, 205, 207 NCI, 1, 95, 133, 197, 202 Necrosis, 38, 51, 189, 195, 197 Need, 111, 117, 125, 129, 151, 173, 197, 217 Neoplasia, 138, 198 Neoplasm, 198, 218 Neoplastic, 193, 198 Nephropathy, 191, 198
228 Narcolepsy
Nerve, 6, 100, 163, 166, 168, 178, 193, 194, 196, 198, 199, 200, 201, 203, 205, 210, 214, 218, 219 Nerve Endings, 100, 198 Neural, 17, 21, 22, 32, 35, 36, 164, 178, 187, 196, 198, 206, 211, 213 Neuralgia, 112, 198 Neuroblastoma, 20, 198 Neuroeffector Junction, 198 Neuroendocrine, 14, 198 Neuroglia, 185, 198 Neurologic, 56, 89, 144, 198 Neuromuscular, 163, 198 Neuromuscular Junction, 163, 198 Neuronal, 6, 15, 22, 31, 34, 81, 105, 106, 108, 112, 197, 198 Neuropathy, 105, 106, 198 Neuropeptide, 5, 8, 13, 14, 16, 198 Neuropharmacology, 28, 46, 47, 48, 59, 66, 199 Neurophysiology, 14, 40, 41, 44, 64, 65, 69, 72, 73, 76, 77, 86, 178, 199 Neurosis, 101, 199 Neurotic, 101, 199, 219 Neurotoxin, 5, 199 Neurotransmitters, 7, 22, 34, 199, 205, 212 Neutrons, 164, 199, 208 Nicotine, 100, 105, 106, 199 Nitric Oxide, 108, 199 Nitrogen, 164, 165, 199, 218 Norepinephrine, 22, 99, 100, 105, 106, 163, 178, 180, 199, 203, 212 Nuclear, 34, 168, 176, 181, 183, 192, 193, 197, 199, 216 Nuclei, 6, 12, 22, 164, 165, 176, 181, 182, 185, 190, 193, 199, 200, 204, 207, 211, 219 Nucleic acid, 104, 185, 189, 199 Nucleus Accumbens, 14, 200 Nursing Care, 88, 200 O Ocular, 12, 64, 200 Odds Ratio, 200, 209 Ointments, 180, 200 Oncogene, 31, 138, 200 Opacity, 178, 200 Opium, 196, 200 Optic Chiasm, 188, 200, 205 Optic Nerve, 200, 207, 209 Optic Nerve Diseases, 200, 207 Osteoarthritis, 105, 106, 200 Overweight, 83, 110, 111, 201 Oxidation, 163, 169, 177, 201
Oxidation-Reduction, 169, 201 Oxygen Consumption, 107, 201, 209 P Palate, 201, 212, 219 Palliative, 201, 216 Palsy, 35, 201, 213 Pancreas, 163, 179, 192, 201, 213 Pancreatic, 138, 201 Pancreatic cancer, 138, 201 Panic, 32, 188, 201 Papilledema, 201, 207 Paralysis, 6, 89, 101, 102, 160, 177, 194, 201, 213 Parasitic, 166, 186, 201 Parasympathomimetic, 167, 201 Paroxetine, 64, 201 Paroxysmal, 32, 65, 138, 166, 186, 201 Partial remission, 201, 209 Pathogenesis, 22, 88, 201 Pathologic, 29, 177, 188, 201, 207 Pathologies, 35, 202 Pathophysiology, 7, 27, 48, 54, 202 Patient Compliance, 112, 202 Patient Education, 125, 154, 156, 161, 202 PDQ, 145, 202 Pediatrics, 29, 56, 89, 103, 202 Pedigree, 10, 202 Pelvic, 202, 206 Pemoline, 99, 128, 202 Penicillin, 166, 202 Pepsin, 174, 202 Pepsin A, 174, 202 Peptide, 3, 13, 21, 22, 24, 34, 35, 43, 169, 173, 191, 202, 204, 206, 217 Peptide T, 13, 34, 202 Perception, 186, 202, 210 Perfusion, 23, 188, 202 Pericardium, 202, 215 Peripheral Nervous System, 201, 202, 205, 213, 214 PH, 64, 170, 203 Pharmaceutical Solutions, 180, 203 Pharmacokinetic, 31, 203 Pharmacologic, 19, 166, 203, 217, 219 Pharmacotherapy, 40, 46, 50, 203 Phenotype, 8, 203 Phenyl, 111, 203 Phenylalanine, 99, 100, 202, 203, 218 Phenylpropanolamine, 100, 203 Phosphodiesterase, 105, 203 Phospholipases, 203, 212 Phospholipids, 184, 190, 203
Index 229
Phosphorus, 171, 203 Photoreceptors, 9, 176, 203, 210 Phototherapy, 203, 210 Phototransduction, 9, 203, 210 Physiologic, 29, 164, 169, 180, 194, 203, 208 Physiology, 14, 33, 35, 163, 199, 204 Pigment, 194, 204 Pilot study, 73, 204 Pineal Body, 182, 204 Pineal gland, 76, 204 Plants, 164, 171, 174, 185, 199, 204, 217 Plasma, 54, 66, 109, 166, 172, 186, 187, 204, 211 Plasma cells, 166, 204 Platelet Activation, 204, 212 Platelet Aggregation, 165, 199, 204 Platelets, 199, 204 Pleomorphic, 200, 204 Poisoning, 183, 190, 197, 204 Polycystic, 98, 109, 110, 139, 204 Polymers, 101, 204, 206 Polymorphic, 19, 204 Polymorphism, 19, 38, 55, 72, 74, 204 Polypeptide, 165, 202, 204, 206, 213, 220 Polysaccharide, 167, 204 Pons, 6, 170, 172, 184, 204, 209 Pontine, 6, 23, 39, 67, 80, 205 Posterior, 17, 165, 168, 172, 180, 182, 201, 204, 205, 219 Postsynaptic, 31, 198, 205, 212, 215 Post-synaptic, 35, 205 Postural, 8, 205 Potassium, 98, 109, 110, 205 Potassium Channels, 98, 109, 110, 205 Potentiate, 112, 205 Potentiation, 205, 212 Practice Guidelines, 136, 147, 205 Prazosin, 103, 205 Precursor, 99, 100, 180, 181, 182, 192, 199, 203, 205, 218 Predisposition, 54, 205 Premenstrual, 100, 105, 106, 205 Premenstrual Syndrome, 100, 105, 106, 205 Preoptic Area, 15, 31, 36, 205 Presynaptic, 28, 198, 205, 215 Presynaptic Terminals, 198, 205 Prevalence, 7, 11, 24, 25, 26, 28, 67, 74, 200, 205 Probe, 195, 206 Prognostic factor, 206, 215 Progression, 166, 206, 211
Progressive, 172, 173, 178, 180, 186, 197, 200, 204, 206, 218 Projection, 15, 22, 199, 200, 206, 208 Prolactin, 170, 206 Promoter, 72, 206 Prophase, 206, 215 Prophylaxis, 110, 112, 206 Propranolol, 101, 106, 206 Prosencephalon, 179, 206, 216 Prospective study, 24, 25, 26, 27, 206 Prostate, 138, 206 Protein C, 3, 16, 21, 165, 185, 206 Protein S, 12, 14, 116, 139, 169, 179, 185, 206 Proteins, 12, 16, 20, 22, 98, 110, 165, 167, 172, 175, 184, 195, 199, 202, 204, 206, 208, 211, 216, 217 Proteolytic, 164, 175, 206 Protocol, 27, 93, 207 Protons, 164, 188, 191, 207, 208 Protriptyline, 47, 207 Proximal, 108, 179, 205, 207, 211 Proxy, 103, 207 Pseudotumor Cerebri, 59, 190, 207 Psoriasis, 108, 207 Psychiatric, 6, 8, 18, 32, 194, 207, 212 Psychic, 192, 199, 207, 211 Psychosis, 98, 110, 167, 207 Psychotomimetic, 165, 179, 207 Public Policy, 135, 207 Publishing, 36, 149, 207 Pulmonary, 66, 170, 176, 207, 219 Pulmonary Artery, 170, 207, 219 Pulse, 13, 196, 207 Pyridoxal, 208, 217 Q Quality of Life, 16, 29, 51, 150, 208, 215 R Race, 100, 105, 106, 149, 180, 208 Raclopride, 73, 208 Radiation, 101, 166, 168, 182, 191, 193, 208, 220 Radioactive, 168, 188, 189, 193, 196, 199, 208 Randomized, 29, 68, 94, 181, 208 Reality Testing, 207, 208 Receptor, 3, 6, 13, 14, 16, 20, 22, 23, 28, 30, 33, 35, 64, 70, 72, 74, 75, 104, 111, 163, 167, 180, 185, 202, 208, 211, 212 Receptors, Serotonin, 208, 211 Recombinant, 12, 16, 208 Rectum, 170, 179, 184, 189, 191, 206, 208
230 Narcolepsy
Recur, 208, 210 Recurrence, 169, 174, 193, 208, 210 Red Nucleus, 168, 208 Refer, 1, 175, 180, 192, 199, 207, 208 Reflex, 100, 105, 183, 208 Refraction, 208, 213 Refractory, 49, 208 Regimen, 181, 202, 203, 208 Relative risk, 53, 208 Relaxant, 209 Reliability, 54, 209 Remission, 169, 193, 208, 209 Research Design, 29, 209 Research Support, 27, 209 Respiration, 6, 32, 101, 167, 171, 177, 195, 209 Respirator, 12, 209, 219 Respiratory failure, 18, 209, 219 Restless legs, 27, 148, 209 Reticular, 8, 23, 34, 80, 209 Reticular Formation, 23, 80, 209 Retina, 176, 198, 200, 203, 209, 210 Retinal, 200, 203, 209 Retinoblastoma, 138, 209 Rheumatism, 209 Rheumatoid, 35, 209 Rheumatoid arthritis, 35, 209 Rhinorrhea, 98, 109, 110, 210 Rigidity, 112, 190, 204, 210 Risk factor, 11, 33, 34, 182, 206, 208, 210 Rods, 203, 209, 210, 219 S Salivary, 70, 179, 201, 210 Salivary glands, 179, 210 Schizoid, 210, 220 Schizophrenia, 4, 8, 15, 63, 67, 71, 101, 110, 112, 210, 220 Schizophrenia, Catatonic, 101, 210 Schizotypal Personality Disorder, 210, 220 Sclerosis, 138, 139, 196, 210 Screening, 4, 41, 42, 71, 174, 202, 210 Seasonal Affective Disorder, 100, 105, 109, 210 Second Messenger Systems, 199, 210 Secretion, 69, 98, 110, 170, 174, 187, 190, 196, 210, 211, 219 Secretory, 98, 109, 110, 111, 198, 210, 215 Sedative, 13, 103, 174, 188, 210, 219 Sedatives, Barbiturate, 168, 210 Sedentary, 12, 210 Segregation, 21, 71, 210
Seizures, 98, 101, 110, 144, 160, 167, 201, 211 Selegiline, 69, 71, 82, 211 Semen, 206, 211 Semisynthetic, 170, 211 Sensor, 12, 211 Septal, 192, 211 Septal Nuclei, 192, 211 Sequence Analysis, 52, 211 Sequence Homology, 202, 211 Serology, 53, 211 Serotonin, 13, 31, 99, 105, 106, 167, 178, 184, 196, 201, 203, 208, 211, 212, 218 Serum, 16, 165, 175, 211, 218 Sex Characteristics, 163, 211 Sex Determination, 139, 211 Shock, 108, 111, 211, 218 Shunt, 59, 212 Sibutramine, 104, 105, 106, 212 Side effect, 125, 127, 129, 163, 167, 172, 194, 207, 212, 215, 217 Signal Transduction, 20, 22, 190, 212 Signs and Symptoms, 101, 209, 212 Skeletal, 6, 177, 197, 212, 213 Skeleton, 191, 212 Skull, 177, 190, 212, 216 Sleep apnea, 16, 18, 24, 25, 26, 29, 35, 42, 43, 56, 63, 70, 75, 77, 150, 212 Sleep Deprivation, 15, 58, 212 Sleep Paralysis, 33, 91, 102, 104, 212 Small intestine, 180, 187, 190, 212 Smooth muscle, 101, 164, 165, 187, 196, 212, 213, 214 Snoring, 148, 212 Social Class, 149, 212 Social Environment, 208, 213 Sodium, 93, 107, 112, 203, 213 Sodium Channels, 203, 213 Sodium Oxybate, 93, 107, 213 Soma, 65, 213 Somatic, 163, 187, 192, 194, 202, 213 Somatostatin, 13, 213 Somnolence, 43, 49, 160, 213 Spasm, 176, 194, 213 Spastic, 191, 213 Spasticity, 112, 213 Spatial disorientation, 180, 213 Specialist, 44, 150, 213 Species, 103, 164, 177, 182, 187, 194, 196, 201, 208, 211, 213, 214, 218, 219, 220 Specificity, 17, 30, 164, 166, 213 Spectrum, 7, 33, 40, 213
Index 231
Sperm, 173, 213 Spinal cord, 14, 22, 108, 168, 170, 172, 173, 194, 198, 202, 208, 214 Spondylitis, 35, 214 Sporadic, 21, 209, 214 Stasis, 60, 87, 214 Steroid, 177, 214 Stimulant, 7, 19, 30, 73, 93, 165, 167, 178, 187, 195, 202, 214 Stimulus, 14, 89, 180, 181, 183, 186, 191, 208, 214, 216 Stomach, 111, 163, 179, 183, 184, 185, 187, 197, 202, 212, 214 Stool, 189, 191, 214 Strand, 20, 214 Stress, 32, 171, 177, 191, 197, 205, 209, 214 Striatum, 12, 200, 214 Stroke, 94, 95, 99, 107, 134, 145, 146, 147, 148, 171, 214 Stupor, 197, 210, 214 Subarachnoid, 59, 184, 186, 214 Subclinical, 189, 211, 214 Subcutaneous, 108, 163, 214 Subspecies, 213, 214 Substance P, 194, 210, 214 Subthalamus, 179, 214 Support group, 150, 215 Supportive care, 202, 215 Suppression, 6, 8, 31, 32, 57, 98, 100, 108, 110, 215 Survival Analysis, 34, 215 Sympathomimetic, 165, 178, 180, 182, 195, 199, 203, 215, 218 Symphysis, 206, 215 Symptomatic, 15, 54, 215 Symptomatology, 47, 67, 215 Synapses, 198, 199, 215 Synapsis, 215 Synaptic, 15, 34, 35, 98, 99, 110, 199, 212, 215 Synaptic Transmission, 98, 110, 199, 215 Systemic, 63, 108, 128, 170, 179, 182, 189, 190, 215 Systemic lupus erythematosus, 63, 215 Systolic, 188, 215 T Telangiectasia, 139, 216 Telencephalon, 168, 206, 216 Temporal, 165, 186, 187, 216 Temporal Lobe, 165, 216 Testicular, 65, 216 Testis, 216
Thalamic, 168, 182, 216 Thalamic Diseases, 168, 216 Thalamus, 179, 182, 192, 214, 216 Therapeutics, 14, 129, 196, 216 Third Ventricle, 182, 188, 204, 216 Threonine, 202, 216 Threshold, 5, 183, 188, 216 Thrombin, 204, 206, 216 Thrombomodulin, 206, 216 Thrombosis, 206, 214, 216 Thymus, 216, 218 Thyroid, 125, 188, 216, 217, 218 Thyroid Gland, 188, 216, 217 Thyroid Hormones, 216, 217, 218 Thyroiditis, 19, 217 Thyrotropin, 80, 217 Thyroxine, 203, 217 Tidal Volume, 32, 217 Tinnitus, 110, 112, 207, 217, 219 Tolerance, 100, 108, 111, 217 Tomography, 217 Tonic, 18, 217 Toxic, iv, 12, 108, 169, 176, 177, 179, 182, 183, 188, 193, 198, 199, 217 Toxicity, 30, 109, 180, 217 Toxicology, 40, 88, 101, 136, 217 Toxins, 167, 181, 189, 196, 217 Trachea, 216, 217 Transaminase, 107, 217 Transduction, 212, 217 Transfection, 169, 218 Translational, 16, 218 Transmitter, 6, 14, 22, 163, 168, 180, 191, 194, 198, 199, 215, 218 Transplantation, 19, 173, 193, 218 Transplantation Immunology, 19, 218 Trauma, 32, 101, 197, 218 Tricyclic, 128, 178, 188, 193, 207, 218 Trigeminal, 112, 218 Tryptophan, 211, 218 Tubercle, 200, 218 Tuberculosis, 176, 193, 218 Tuberous Sclerosis, 139, 144, 218 Tumor Necrosis Factor, 66, 72, 108, 218 Tumour, 38, 51, 218 Tyramine, 196, 218 Tyrosine, 59, 81, 82, 90, 99, 100, 180, 218 U Unconscious, 166, 188, 218 Urethra, 206, 218, 219 Urinary, 98, 109, 110, 111, 189, 205, 218, 219
232 Narcolepsy
Urinary Retention, 205, 219 Urine, 24, 25, 26, 27, 169, 187, 189, 218, 219 Uterus, 173, 184, 194, 219 Uvula, 212, 219 V Vaccine, 163, 207, 219 Vacuoles, 181, 219 Vagina, 173, 178, 194, 219 Valerian, 144, 219 Vascular, 98, 109, 110, 164, 182, 186, 189, 199, 216, 219 Vasodilator, 170, 180, 187, 219 Vein, 168, 190, 199, 219 Venous, 168, 206, 219 Ventilator, 209, 219 Ventral, 13, 188, 200, 205, 219 Ventricle, 165, 172, 187, 200, 207, 215, 219 Vertebrae, 214, 219 Vestibulocochlear Nerve, 217, 219 Vestibulocochlear Nerve Diseases, 217, 219 Veterinary Medicine, 81, 135, 219 Vibrio, 173, 219, 220 Vibrio cholerae, 173, 220 Villous, 172, 220
Virulence, 217, 220 Viruses, 167, 195, 219, 220 Visceral, 192, 220 Visual field, 200, 207, 220 Vitamin A, 190, 220 Vitro, 28, 220 Vivo, 28, 34, 220 W Wakefulness, 6, 8, 12, 17, 21, 23, 32, 33, 35, 70, 72, 73, 160, 220 Weight Gain, 105, 106, 210, 220 White blood cell, 166, 192, 193, 196, 204, 220 Windpipe, 216, 220 Withdrawal, 4, 10, 30, 101, 107, 108, 220 X Xenograft, 166, 218, 220 X-ray, 170, 175, 176, 193, 199, 220 Y Yeasts, 203, 220 Yohimbine, 46, 80, 220 Z Zygote, 176, 220 Zymogen, 206, 220
Index 233
234 Narcolepsy
Index 235
236 Narcolepsy
