Sleep Deprivation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

SLEEP

DEPRIVATION 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., 1960Sleep Deprivation: 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: 0-597-84215-9 1. Sleep Deprivation-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 sleep deprivation. 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 SLEEP DEPRIVATION ................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Sleep Deprivation.......................................................................... 6 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND SLEEP DEPRIVATION ..................................................................... 109 Overview.................................................................................................................................... 109 Finding Nutrition Studies on Sleep Deprivation ...................................................................... 109 Federal Resources on Nutrition ................................................................................................. 113 Additional Web Resources ......................................................................................................... 114 CHAPTER 3. ALTERNATIVE MEDICINE AND SLEEP DEPRIVATION ............................................... 115 Overview.................................................................................................................................... 115 National Center for Complementary and Alternative Medicine................................................ 115 Additional Web Resources ......................................................................................................... 122 General References ..................................................................................................................... 122 CHAPTER 4. DISSERTATIONS ON SLEEP DEPRIVATION ................................................................. 125 Overview.................................................................................................................................... 125 Dissertations on Sleep Deprivation ........................................................................................... 125 Keeping Current ........................................................................................................................ 126 CHAPTER 5. CLINICAL TRIALS AND SLEEP DEPRIVATION ........................................................... 127 Overview.................................................................................................................................... 127 Recent Trials on Sleep Deprivation ........................................................................................... 127 Keeping Current on Clinical Trials ........................................................................................... 128 CHAPTER 6. PATENTS ON SLEEP DEPRIVATION ........................................................................... 131 Overview.................................................................................................................................... 131 Patents on Sleep Deprivation..................................................................................................... 131 Patent Applications on Sleep Deprivation................................................................................. 133 Keeping Current ........................................................................................................................ 136 CHAPTER 7. BOOKS ON SLEEP DEPRIVATION ............................................................................... 137 Overview.................................................................................................................................... 137 Book Summaries: Online Booksellers......................................................................................... 137 The National Library of Medicine Book Index ........................................................................... 138 Chapters on Sleep Deprivation .................................................................................................. 139 CHAPTER 8. MULTIMEDIA ON SLEEP DEPRIVATION .................................................................... 141 Overview.................................................................................................................................... 141 Bibliography: Multimedia on Sleep Deprivation ....................................................................... 141 CHAPTER 9. PERIODICALS AND NEWS ON SLEEP DEPRIVATION ................................................. 143 Overview.................................................................................................................................... 143 News Services and Press Releases.............................................................................................. 143 Academic Periodicals covering Sleep Deprivation ..................................................................... 146 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 149 Overview.................................................................................................................................... 149 NIH Guidelines.......................................................................................................................... 149 NIH Databases........................................................................................................................... 151 Other Commercial Databases..................................................................................................... 153 APPENDIX B. PATIENT RESOURCES ............................................................................................... 155 Overview.................................................................................................................................... 155 Patient Guideline Sources.......................................................................................................... 155 Finding Associations.................................................................................................................. 158 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 161

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Overview.................................................................................................................................... 161 Preparation................................................................................................................................. 161 Finding a Local Medical Library................................................................................................ 161 Medical Libraries in the U.S. and Canada ................................................................................. 161 ONLINE GLOSSARIES................................................................................................................ 167 Online Dictionary Directories ................................................................................................... 167 SLEEP DEPRIVATION DICTIONARY..................................................................................... 169 INDEX .............................................................................................................................................. 227

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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 sleep deprivation 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 sleep deprivation, 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 sleep deprivation, 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 sleep deprivation. 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 sleep deprivation, 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 sleep deprivation. 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 SLEEP DEPRIVATION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on sleep deprivation.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and sleep deprivation, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “sleep deprivation” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Sleep Disorders: Overview and Relationship to Orofacial Pain Source: Dental Clinics of North America. 41(2): 189-209. April 1997. Summary: In this article, the author considers sleep disorders and their relationship to orofacial pain. The author notes that when pain is present, sleep becomes disrupted. Consequently, the days are seemingly longer and normal activities are more difficult because of inadequate rest. The author briefly reviews the history of sleep disorders, normal sleep, the impact of temperature on sleep, sleep deprivation, and the potential impact of drug ingestion. The author then introduces sleep disorders in general (including their classification) and discusses specific sleep disorders related to orofacial pain: sleep apnea, insomnia, primary snoring (upper airway resistance syndrome), periodic limb movement disorders, and sleep bruxism (grinding the teeth). Other sleep

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related disorders that occur less frequently but may contribute to an orofacial pain problem are also discussed, including posttraumatic hypersomnia, sleep related asthma, sleep related gastroesophageal reflux, shift work sleep disorders, irregular sleep wake pattern, and sleep deprivation in Lyme disease. The article concludes with brief sections on related painful conditions and sleep, including burning mouth syndrome, rheumatoid arthritis, menopause, trigeminal neuralgia, glossopharyngeal neuralgia, Lyme disease, headache disorders, temperal arteritis (headache), temporomandibular disorders, and atypical odontalgia. 5 figures. 2 tables. 35 references. •

Self-Care Regimens for Patients With Interstitial Cystitis Source: Urologic Clinics of North America. 21(1): 121-130. February 1994. Contact: Available from W.B. Saunders Company. The Curtis Center, Independence Square West, Philadelphia, PA 19106. (800) 654-2452. Summary: In this article, the author explores self-care regimens for patients with interstitial cystitis (IC). The author notes that coping with interstitial cystitis requires dealing with chronic pain and sleep deprivation, acceptance of a difficult diagnostic process, and patience during a trial-and-error regimen to find the combination of therapeutic modalities that can achieve a remission in symptoms. Topics covered include the systemic manifestations of IC; gynecologic manifestations of IC; the typical flare and remission course of IC; etiology; diagnostic work-up; recommended approach to patient management; and self-care treatment regimens, including dietary manipulation, nutritional supplements, stress reduction, exercise, bladder retraining, and bladder instillations; and dealing with chronic pain. 2 figures. 5 tables. 51 references.

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Sleep Debt A Wake-Up Call Source: Diabetes Self-Management. 19(2): 67-71. March-April 2002. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Website: www.diabetes-self-mgmt.com. Summary: Most research on sleep deprivation has focused on its cognitive (thinking) effects, but recent studies show that sleep debt affects the body as well as the mind. These studies suggest that sleep deprivation may lead to weight gain and might also worsen insulin resistance. This article offers readers with diabetes information about the impact of sleep debt. The author discusses theories as to why humans sleep, the two basic phases of sleep, six different stages of sleep, sociological changes that have resulted in less sleep, research on the effects of sleep loss, carbohydrate metabolism and how it changes with sleep loss, sleep and insulin sensitivity, and strategies to increase the likelihood of getting regular, healthy amounts of sleep. One side bar explains sleep apnea, a condition in which breathing stops repeatedly during sleep.

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Pruritus in End-Stage Renal Disease Source: ANNA Journal. American Nephrology Nurses' Association Journal. 21(2): 147153. April 1994. Contact: Available from American Nephrology Nurses' Association. Box 56, East Holly Avenue, Pitman, NJ 08071. (609) 256-2320. Summary: Pruritus is common in end-stage renal disease (ESRD) clients, and can be severe. The author of this article reviews the anatomy and physiology of the skin,

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describes the pathophysiology of pruritus; discusses proposed etiologies; reviews an assessment for an ESRD client with pruritus; and discusses the collaborative management of pruritis in ESRD. The author notes that assessment tools are available to nurses and clients to grade the severity, frequency, distribution, and sleep deprivation experienced with the itching. Various treatments have been used to manage pruritus in ESRD with limited success. 2 figures. 34 references. (AA-M). •

Practical Strategies for Nocturia in Adults Source: Patient Care. 33(8): 147-148, 153-154, 157-158. April 30, 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article reviews the practical care strategies that can be used to manage the adult patient with nocturia (urination at night). A common reason for visits to urologists, nocturia causes sleep deprivation and increases the risk of traumatic injury due to falls, especially among the elderly. The authors stress that, despite a variety of possible etiologies, nocturia can be classified, diagnosed, and treated with a sensible strategy that combines a little math, a voiding diary, and thorough investigative techniques. Treatment typically involves attempts to resolve either detrusor instability or bladder outlet obstruction. Although one or both of these conditions may exist in a patient who reports nocturia, the authors note that treatment may fail because of the often overlooked component of nocturnal polyuria (NP), or excessive nighttime urine production. Treatment options discussed in the article include compressive stockings, afternoon naps, diuretics, and antidiuretic hormone. The authors recommend that initial treatment should be directed at the NP component of the problem, unless its contribution is minor in comparison to the magnitude of noctural detrusor overactivity (NDO). Patient care algorithms are provided to help the reader through the process of diagnosis and treatment. 2 figures. 3 tables. 15 references.

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Treating Sleep Disorders in Patients With Fibromyalgia Source: Journal of Musculoskeletal Medicine. 14(6):25-28,33-34; June 1997. Summary: This journal article for health professionals reviews current knowledge about sleep disorders in patients with fibromyalgia and the treatment strategies currently used. Sleep disturbance may be central to the fibromyalgia syndrome. Many patients have difficulty in falling and staying asleep and awaken unrefreshed with intensified morning aching. Alpha-delta sleep, in which internally triggered arousal results in delta sleep deprivation, appears responsible. Moreover, such triggers may also lead to depressed and anxious mood, fatigue, morning stiffness, and musculoskeletal pain, which, in turn, contribute to the nonrestorative sleep cycle. Success in improving sleep is greatest when general approaches and specific sleep interventions are combined. Psychotherapy, behavioral therapy, and exercise may lead to better sleep habits and symptomatic relief. Tricyclic agents improve sleep and overall functioning. Benzodiazepines administered with nonsteroidal anti-inflammatory drugs may improve sleep and decrease tenderness. 29 references and 2 tables. (AA-M).

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Neuroscience and Endocrinology of Fibromyalgia, The Source: Journal of Musculoskeletal Pain. 6(3): i-xiv,1-105. 1998. Summary: This journal provides health professionals with an overview of the neuroscience and endocrinology of fibromyalgia syndrome (FMS). Articles in this issue

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are from participants who attended the second National Institutes of Health Conference on FMS. The conference focused on the process of pain signal transmission to perception, sleep physiology, and neuroendocrine function. Contributors in the chronic pain segment of the conference provided evidence that the central nervous system (CNS) may be primarily involved in FMS through altered pain modulatory mechanisms, presented an overview of how peripheral tissue or nerve injury often results in hyperalgesia characterized by increased sensitivity to painful stimuli, and described a model for chronic pain that suggests that FMS is a disorder characterized by abnormal CNS processing of sensory or nociceptive stimuli. Other contributors in this segment examined the role of substance P in FMS, discussed animal models of gender differences in pain and analgesia, and reviewed the evidence for cognitive behavioral interventions in the rheumatic diseases. Contributors in the neuroendocrine segment of the conference provided an overview of the physiology and phenomenology of the stress system and its complex interactions with other endocrine and neurological pathways and with the immune system, reviewed studies addressing the effects of early environmental exposures on the stress system, discussed interactions between the hypothalamic pituitary adrenal axis and hypothalamic pituitary gonadal axis, considered the responses of the sympathetic nervous and adrenomedullary hormonal systems to stressors, and reviewed research supporting an association between FMS and perturbed function of stress response systems and other neuroendocrine axes. Sleep segment topics included animal models of sleep and sleep deprivation influences on behavior and immune function in animals. 8 figures, 3 tables, and numerous references.

Federally Funded Research on Sleep Deprivation The U.S. Government supports a variety of research studies relating to sleep deprivation. 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 sleep deprivation. 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 sleep deprivation. The following is typical of the type of information found when searching the CRISP database for sleep deprivation: •

Project Title: ADIPOSITY, BP & THE INFLAMMATORY RESPONSE TO SLEEP LOSS Principal Investigator & Institution: Mullington, Janet M.; Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Summary: (provided by applicant): Recent studies have shown that mediators of inflammation, useful in predicting risk of developing cardiovascular disease in healthy asymptomatic individuals, are also increased by experimental sleep deprivation. Low basal increases in inflammatory markers are also seen in "metabolic syndrome" and we hypothesize that inadequate or insufficient sleep may be a pivotal contributing factor in the development of metabolic syndrome. We will test the hypothesis that basal changes in inflammation are actually secondary to cardiovacular factors associated with shear stress, by blocking the increase of blood pressure that is known to ensue during sleep deprivation. We expect that blocking the sleep deprivation associated increase in blood pressure will prevent the rise of inflammatory markers. We will also test the hypothesis that moderately adipose individuals are at greater risk to suffer the inflammatory and autonomic consequences of acute sleep deprivation. In screening data from this study we will also investigate the relationship between adiposity, cardiovascular fitness, Creactive protein and habitual sleep duration and quality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADOLESCENT ADHD: SLEEP, SYMPTOMS, AND MEDICATION Principal Investigator & Institution: Fallone, Gahan P.; Emma Pendleton Bradley Hospital East Providence, Ri 02915 Timing: Fiscal Year 2002; Project Start 03-JUN-2002; Project End 31-MAY-2004 Summary: Attention-Deficit/Hyperactivity (ADHD) is a developmental disorder characterized by age-inappropriate levels of restlessness, impulsivity, and/or inattention that is increasingly diagnosed and treated among adolescents. Research performed in our lab has demonstrated that normal adolescents are at heightened risk for insufficient sleep and are likely to display behavioral and academic problems due to sleep restriction. Among adolescents predisposed to behavioral and academic difficulties, such as those with ADHD, the impact of shortened sleep may be amplified. Characteristics of ADHD may increase both the risk for and vulnerability to restricted sleep. In addition, restricted sleep may affect attitudes toward treatment, particularly since psychostimulant medication is a common treatment for ADHD and also an effective countermeasure for the effects of restricted sleep. The Exploratory/Developmental Grant (R21) Program was selected because the proposed project involves "research directions requiring preliminary testing and development" and uses "approaches new to a substantive area". The projects applies techniques and expertise developed describing sleep in normal adolescents to the exploration of sleep patterns and the response to restricted sleep among adolescents with ADHD. Study 1 confirms the validity of the actigraphy algorithm derived in non-ADHD samples for measuring sleep/wake states in ADHD adolescents, using laboratory-based nocturnal polysomography as the research standard. Actigraphy is then used to assist in describing self-selected sleep patterns and verifying compliance with assigned sleep schedules in Study 2. Study 2 uses a 3-phrase protocol to explore sleep- patterns, daytime sleepiness, ADHD symptoms, perceived need for medication, and medication use under self-selected, extended, and restricted sleep conditions. We hypothesize that self-selected sleep of adolescents with ADHD will be shortened on school nights. Further, under conditions of restricted sleep, we predict that adolescents with ADHD will show increased sleepiness, increased ADHD symptom severity, and increased perceived need for psychostimulant medication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADULT FAILURE TO THRIVE IN LONG-TERM VENTILATOR PATIENTS Principal Investigator & Institution: Higgins, Patricia A.; None; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2005 Summary: Long-term ventilator (LTV) patients represent a growing population that consumes considerable health care resources. Although the majority of critically ill patients require short-term ventilator support, LTV patients may require mechanical ventilation and thus, intensive care hospitalization for weeks or months. Prolonged mechanical ventilation usually involves a lengthy weaning period (an interval in which mechanical ventilator support is gradually withdrawn). To date, much of the research on LTV patients has focused on respiratory parameters that predict weaning outcome and mortality. There are indications, however, that factors such as malnutrition, mood state, social isolation, and poor sleep patterns may be as significant as respiratory parameters in predicting outcomes of LTV patients. Little is known about these factors in LTV patients but they are associated with adult failure to thrive (FTT), a syndrome defined as a lower than expected level of functioning that frequently is associated with nutritional deficits, depressed mood state, and social isolation. In addition to the need to assess factors that affect respiratory functioning in LTV patients, there is increasing recognition that weaning is a process, not a single incident. The proposed research will use a prospective longitudinal design to describe weaning patterns and patterns of FTTrelated variables (nutrition, mood state, social isolation, and sleep) in 300 LTV patients. Descriptive statistics will be used to characterize this patient population and graphic analysis will be used to characterize patterns of change in the variables over time and illustrate between-group variability. Multivariate analyses will investigate the relationship between FTT variables and four outcome variables: discharge disposition, length of stay, weaning outcome, and readmit status. Through identification of factors that can be modified by nurses (e.g., nutritional adequacy, sleep habits, support systems, or mood state), research about weaning and FTT variables in LTV patients will provide data for future intervention studies. It has the potential, therefore, to decrease the morbidity and mortality associated with adult FTT and long-term mechanical ventilation and it will help nurses, patients and families prepare for post-hospital care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AFFECT REGULATION AND ADOLESCENT BRAIN MATURATION Principal Investigator & Institution: Dahl, Ronald E.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): This application describes a Research Network aimed at conceptual and methodological advances in understanding affect dysregulation in adolescence. The central theme for this project is the development and refinement of measures of affect regulation that can be used to investigate neurobehavioral systems in adolescents within a developmental framework. These include tasks that can be used in functional MRI and ERP (event-related potential) studies to examine the development of neurobehavioral systems in both clinical and normative populations of adolescents. It is also important to devise experimental paradigms that address clinically relevant and ecologically valid aspects of emotion and its regulation. This will require developing better conceptual models and formulating specific hypotheses about affective changes in developmental pathways of emotional

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disorders in adolescence. The long-term goals of this work are to address clinically relevant questions-to identify developmental pathways and mechanisms of affect dysregulation that can inform treatment strategies for early-onset depression, anxiety, and other emotional disorders emerging in adolescence. We focus on adolescence because this developmental phase represents a period of increased vulnerabilities for emotional disorders, yet also presents opportunities for early intervention. Ultimately, mechanistic understanding of the development of affect regulation can lead to prevention strategies targeting high-risk populations prior to the onset of more serious emotional disorders. A deeper understanding of affect regulation in adolescence may also provide insights into behaviors such as increased sensation seeking, risk-taking, and substance use-common behaviors in adolescence that can lead to serious consequences. The specific aims of this research network are: (1) To develop and refine fMRI and ERP tasks of emotion regulation that can be used in clinical and developmental studies of older children and adolescents. (2) To develop and refine behavioral and experience-sampling methods of assessing emotion and its regulation in the natural environments of adolescents. (3) To improve heuristic models of affect regulation and dysregulation during adolescent development within a cognitive/affective neuroscience framework. (4) To provide outstanding interdisciplinary training experiences for young investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALCOHOLISM: SLEEP AND CYTOKINES IN AFRICAN AMERICANS Principal Investigator & Institution: Irwin, Michael R.; Professor; Psychiatry & Biobehav Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAR-2006 Summary: (Provided by applicant): Disturbances of sleep are prominent in alcoholic patients, persist into recovery, and have recently been found to predict those alcoholics who are most likely to relapse. This study hypothesizes that the complex cytokine network is one system that is associated with declines of sleep depth and loss of delta sleep in alcoholics. Basic observations demonstrate that pro-inflammatory and helper T cell type 1/type 2 (Thl/Th2) cytokines have a physiological role in the regulation of sleep with both somnogenic and inhibitory effects depending on the cytokine, dose, and circadian phase. However, translation of these basic mechanisms into the clinical setting is limited, and virtually no study has examined the relationships between cytokine expression and disordered sleep in patients with chronic alcohol dependence. Because evidence further indicates that African American alcoholics are at increased risk for infectious disease morbidity, disordered sleep, and abnormal cytokine expression, this study further proposes to examine the effects of alcohol dependence on sleep and on the relationships between sleep and pro-inflammatory and Thl/Th2 cytokine expression in "at risk" African American alcoholics vs. Euro-American alcoholics and controls. Sleep deprivation serves as a naturalistic probe of sleep regulatory processes to evaluate the capacity of sleep recovery in alcoholics and to test the effects of sleep on immune system functioning. The specific aims of this study are to: 1) evaluate whether alcohol dependence and African American ethnicity are associated with disturbances of sleep including loss of delta sleep and deficits in recovery of delta sleep following sleep deprivation as compared to ethnicity matched controls; 2) establish the impact of sleep on the diurnal- and nocturnal expression of pro-inflammatory-, Thl, and Th2 cytokine levels in African American and Euro- American alcoholics vs. controls; 3) determine the predictive validity of circulating interlekin-6 on delta sleep. This study will advance our

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understanding of the reciprocal relationships between cytokines and sleep in alcohol dependence with implications for answering why sleep is disordered in alcoholics patients and for the development of novel treatments (e.g., cytokine antagonists) for sleep disturbance in alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BASIC MECHANISMS OF DELAYED SLEEP PHASE SYNDROME Principal Investigator & Institution: Wyatt, James K.; Assistant Professor; RushPresbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Delayed Sleep Phase Syndrome (DSPS) describes patients who cannot fall asleep until several hours past their preferred bedtime and have extreme difficulty arising in the morning in order to attend to normal activities (e.g., school, work). This differs from traditional sleep-onset insomnia in that DSPS patients can fall asleep quickly and obtain a normal 8-hr sleep episode, but only at a much-delayed clock hour (e.g., 3 am to 11 pm). Prevalence estimates range from 0.13 percent to 7 percent. Peak onset is in the second and third decades. Possible consequences of this disorders include increased risk for accidents, impaired learning, higher use of alertness-enhancing substances, and lower productivity. The specific aims are: 1. To confirm the hypothesis that the circadian phase, as assessed from core body temperature and salivary melatonin, will be delayed, with week-to-week stability, in patients with Delayed Sleep Phase Syndrome (DSPS) relative to normal-sleeping, ageand gender-matched control subjects. 2. To test the hypothesis that DSPS patients will display the same internal phase relationships between their habitual bedtimes and wake-times, and the circadian phase markers of the minimum of core body temperature, the dim-light melatonin onset, and the fitted maximum of melatonin, but will have a larger amplitude of core body temperature and melatonin rhythms. 3. To test the hypothesis that with a sufficient increase in sleep homeostatic drive, given by the sleep loss incurred during a constant routine protocol, patients with DSPS syndrome will be able to obtain a normal sleep episode at a clock time 3 hours earlier than their habitual, delayed schedule. However, unlike normal control subjects, patients with DSPS return to their baseline pattern of inability to fall asleep at this earlier hour, on a second recovery night of sleep following the constant routine. The proposed investigations fulfill the criteria for the R21 mechanism by offering innovation (e.g., first measurement of temporal stability of phase delay, first measurement of full circadian and sleep parameters), bringing approaches new to an area (e.g., constant routine protocol), and initiating the first step in programmatic research for this investigator (basic mechanisms, diagnostic protocols, and evidence-based treatments for circadian phase disorders, beginning with DSPS). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BEHAVIORAL AND PHYSIOLOGIC PATHOBIOLOGY OF MICE Principal Investigator & Institution: Toth, Linda A.; Professor; Pharmacology; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The Principal Investigator's (PI) long-term career objectives are to: 1) continue to contribute in a meaningful way to basic research on the mechanisms and functions of sleep; 2) enhance resources and training that will support the continued growth of biomedical research at the SIU School of Medicine; and 3)

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advocate the value of and need for the humane and judicious use of animal models to expedite the elucidation of causes, treatments, cures, and prevention of human disease. The PI's past and current service and administrative responsibilities has limited the time available for introducing new research methodology into the laboratory, for mentoring students and other trainees, and for actively participating in collaborative research as a specialist in mouse pathobiology. The relief from institutional service offered by this award will allow the PI the time to accomplish the following Specific Aims: 1) to develop skills in new analytic (microarray technology) and behavioral [sleep deprivation (SD), depression, and anxiety] methodologies for application to interests in delineating the immune modulatory role of sleep; 2) to increase mentoring efforts directed toward both students and faculty; and 3) to initiate collaborations that will promote and support the study of mouse models of human disease. Research goals for this proposal focus on defining the health implications of inadequate sleep. Sleepiness and poor sleep quality broadly influence measures of general health status, particularly impacting perceptions about energy, fatigue, and self-sufficiency. Sleep fragmentation, non-restorative sleep, and inadequate sleep are commonly assumed to adversely impact host defense capabilities. However, these relationships have not been empirically defined. Some studies in animals suggest that inadequate or poor-quality sleep may increase susceptibility to disease, exacerbate symptoms of disease, or delay recuperation. The development and use of an appropriate animal model to evaluate the relationships between sleep, sleep loss, and susceptibility to or recuperation from infectious or inflammatory disease is the primary research goal of this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIORAL INTERVENTION FOR INSOMNIA IN OLDER ADULTS Principal Investigator & Institution: Epstein, Dana R.; U.S. Carl T. Hayden Vet Affairs Med Ctr Affairs Medical Center Phoenix, Az 85012 Timing: Fiscal Year 2002; Project Start 15-SEP-1998; Project End 31-JUL-2004 Summary: Insomnia is a prevalent health problem and frequent complaint of older adults. The majority of research in the non-pharmacological treatment of insomnia has focused on young and middle-aged adults while only a small number of studies have evaluated treatment for late-life insomnia. Knowledge of the intervention or combination of interventions best suited for older adults is limited. Therefore, the purpose of the study is to evaluate and compare the efficacy of single interventions (stimulus control instructions, sleep restriction therapy) and multi- component intervention (stimulus control instructions and sleep restriction therapy) for sleep maintenance insomnia in community dwelling older adults. The study will incorporate multiple sleep measures to determine the short and long-term effects of the interventions on sleep outcomes. The efficiency of the interventions, intervention dosage, compliance with treatment and clinical significance of the outcomes will be addressed. The long-term goal of the research is to provide clinically significant and applicable non-pharmacological, theory driven intervention that effectively addresses the specific insomnia problems of older adulthood. One hundred eighty community dwelling older adults with sleep maintenance insomnia will participate in a randomized controlled study using a waiting-list design. Subjects will be randomly assigned to one of the four conditions: (a) multi- component intervention, (b) stimulus control instructions, (c) sleep restriction therapy, or (d) waiting-list control. There will be a 2week baseline period, a 6-week treatment period, and a 2-week post- treatment period. The waiting-list subjects will receive treatment after the immediate treatment groups

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have completed their treatment and immediate post-treatment phases. Follow up evaluation will occur for 2-week periods at 3 and 12 months post-treatment. Descriptive and inferential statistics will be used to accomplish the specific aims of the study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOPSYCHOSOCIAL MODEL OF SLEEP EDUCATION Principal Investigator & Institution: Owens, Judith A.; Associate Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from the Applicant's Abstract) The purpose of this application is to develop, implement, and evaluate an innovative medical school curriculum at the Brown University School of Medicine in sleep and its disorders. Curriculum organization is based on a biopsychosocial approach to sleep and emphasizes two fundamental educational goals for students: acquisition of a basic foundation in sleep physiology and clinical diagnostic skills related to sleep and sleep disorders in both adults and children, and translation of these basic knowledge, skills, and attitudes about sleep into an organized and comprehensive clinical approach to sleep and sleep disorders in infants, children, and adolescents. Curriculum development will be guided by specific educational principles, namely adult learning theory and instructional technology process, as well as by integration into the Brown MD 2000 competencybased curriculum. Curriculum content will be organized into eight modules, with each addressing a specific sleep issue on a pre-clinical and/or clinical medical school level. Specific educational objectives include the development of a pediatric sleep history instrument; a self-study, self-health and awareness program for medical students on sleep, sleep habits, and the effects of sleep deprivation; development of several video vignettes on sleep problems in children and adolescents; and development of a community education project with medical students giving presentations on adolescent sleep needs and drowsy driving. The curriculum is intended to be modifiable for use in primary care (pediatrics, family medicine) and mental health (child psychology, psychiatry) training programs and other medical school settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHOLINERGIC PHENOTYPE IN MURINE MODELS OF SLEEP Principal Investigator & Institution: Lydic, Ralph B.; Bert La Du Professor of Anesthesia; Anesthesiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Disorders of sleep are estimated to affect 70 million Americans. Sleep is a product of the brain and the cellular mechanisms regulating sleep are incompletely understood. This application is submitted in response to RFA HL-99-001, seeking to stimulate improved molecular, cellular, and systems approaches to investigate sleep in mice. The approach of this application is to use the C57BL/6J mouse (B6) for phenotype characterization of neuronal systems known in other mammals to regulate sleep. The long-term objectives are to advance scientific knowledge by providing data on cholinergic neurotransmission not presently available for mouse. The focus of this application is on muscarinic cholinergic receptors (mAChRs), adenosine A1 receptors, and their associated guanine nucleotide binding proteins (G proteins). Since mammalian sleep is known to be regulated by cholinergic neurotransmission, localizing mAChR subtypes in mouse brain is an essential step for phenotype characterization of the mouse

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as a model for sleep neurobiology. Aim 1 will use in vitro autoradiography to localize and quantify mAChR subtypes in nuclei of B6 mouse forebrain and brain stem. These studies will test the hypothesis that mAChRs in mouse brain stem, basal forebrain, and preoptic hypothalamus parallel the distribution of mAChRs in rat and cat. Activation of mAChRs initiates a transmembrane signal transduction cascade mediated by G proteins. Thus, Aim 2 will use autoradiography to quantify G proteins in the brain regions described by Aim 1. Aim 2 will provide the first phenotype data in B6 mouse localizing cholinergically activated G proteins in brain regions known to regulate sleep and breathing. Concentration-response and antagonist blocking conditions will make it possible to test the hypothesis that G proteins in these nuclei are activated by mAChR stimulation. Cholinergic neuron excitability is modulated by the somnogenic factor adenosine. Aim 3 will test the hypothesis that sleep deprivation alters muscarinic and adenosinergic activation of G proteins in sleep- and breathing-related brain regions. Aim 4 will extend characterization of mouse cholinergic phenotype to the cerebral cortex. Cortical electroencephalographic (EEG) activity comprises a defining measure of sleep, and the EEG is cholinergically modulated. Aim 4 will test the hypothesis that acetylcholine release in frontal association cortex is modulated by muscarinic cholinergic autoreceptors. Aim 4 will further determine the subtype of cortical muscarinic autoreceptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CIRCADIAN AND SLEEP/WAKE ASPECTS OF NOCTURNAL ASTHMA Principal Investigator & Institution: Shea, Steven A.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: There exists a disproportionately high frequency of asthmatic events during the latter half of the usual sleep episode. Patients with nocturnal asthma demonstrate increased morbidity and mortality relative to other patients with asthma. Diurnal studies involving repeated measurements during the sleep/wake cycle, sleep deprivation or shift work suggest the existence of separate sleep and circadian dependent effects on bronchoconstriction. Recent data from established circadian protocols clearly indicate significant circadian rhythms in pulmonary function and respiratory control in healthy subjects, and that indices of airways inflammation have a diurnal rhythm (circadian and sleep/wake cycles not separated) in patients with asthma and healthy controls. The primary aim is to test the hypothesis that asthma severity is affected by separate circadian influences (independent of sleep) and sleep/wake cycle influences (independent of circadian rhythm). The principal dependent variables include bronchoconstriction (spirometry and airways resistance) and asthma symptoms (validated questionnaire and usage of any rescue medication). To overcome methodological problems with previous studies a 'forced desynchrony' protocol will be used, wherein subjects sleep and wake episodes occur at all phases of the circadian cycle. This will be accomplished by scheduling a recurring artificial day length of 28 hours throughout a 10-day protocol in healthy subjects and patients with nocturnal asthma. The specific aims will test the hypotheses that 1) bronchoconstriction is influenced by separate circadian and sleep/wake effects; 2) bronchoconstriction is affected by circadian or sleep/wake influences on airway inflammation; and 3) bronchoconstriction is affected by circadian or sleep/wake influences on sympathovagal balance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CIRCADIAN RHYTHMS AND SLEEP IN FAMILIAL DSPS AND ASPS Principal Investigator & Institution: Zee, Phyllis C.; Professor; Neurology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Tremendous progress in the past few years has led to the identification of several circadian clock genes. This now makes it possible to determine how alterations of human circadian clock genes, and their expression, could lead to differences in circadian and sleep/wake cycle phenotypes. Of particular interest for understanding genetics of the human circadian system are individuals with sleep phase disorders, such as delayed sleep phase syndrome (DSPS) and advanced sleep phase syndrome (ASPS), because recent studies indicate a genetic basis for these disorders. While it is assumed that both ASPS and DSPS are disorders of circadian timing, little is known about how the circadian clock system, or its interaction with sleep processes, are affected in these individuals. Therefore, one of the overall objectives of the proposed studies is to determine the properties (e.g., phase, amplitude, and period) of circadian rhythms under entrained and constant routine conditions in familial ASPS or DSPS. A second objective is to test hypotheses that could explain the mechanisms (i.e., response to light, alterations in period) that underlie the phase disturbance in these conditions. Although it is commonly assumed that sleep per se is normal in the circadian sleep phase disorders, there is some evidence to suggest that the regulation of sleep homeostasis may be altered in DSPS. Therefore, a third specific aim of the proposed studies is to define the sleep-wake characteristics via EEG/polysomnography in DSPS and ASPS subjects during baseline sleep and recovery sleep following sleep deprivation in which the subjects are allowed to begin recovery sleep at a normal or an abnormal circadian time. The approach of studying familial DSPS and ASPS provides a unique opportunity to clearly define circadian and sleep phenotypes in individuals whose sleep/wake cycle is due to intrinsic biological changes and not merely a result of environmental influences and societal pressures. The results of these studies are expected to not only lead to new insights into the regulation of sleep and circadian rhythms in humans, but also to new therapeutic approaches for the treatment of sleep/wake cycle disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONSEQUENCES OF MDMA IN HUMANS Principal Investigator & Institution: Tancer, Manuel E.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by the applicant): 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") use has soared in the past few years despite increasing scientific evidence of adverse consequences. MDMA is perceived as safe by many users despite media reports of deaths and serious medical complications. The mechanism(s) underlying the reported consequences of MDMA use (e.g. hyperthermia, disrupted sleep, mood and anxiety problems) are not known. The goal of the proposed studies is to define both the acute and chronic consequences of MDMA use in humans. Controlled laboratory administration of MDMA (2 mg/kg) will be used to assess the acute effects of MDMA on physiological (thermoregulation, metabolism, and sleep), psychological (mood, anxiety), and cognitive parameters. For an evaluation of chronic effects of MDMA use on mood and anxiety symptoms and cognitive measures, a longitudinal study will be conducted. Specific Aim 1 is to determine the effect of MDMA (compared to placebo) on

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thermoregulation and metabolism under different ambient temperatures (18 and 30 deg C) or under different activity levels (bed rest and moderate exercise [40 percent max V02] for 60 minutes at 23 deg C). Specific Aim 2 is to directly measure the effect of MDMA (compared to placebo, d-amphetamine, or partial sleep deprivation) on sleep time and architecture, cognitive function, mood, subsequent day mood, sleepiness, and cognitive function. Specific Aim 3 is to longitudinally measure cognitive function and psychopathology in novice (1-5 exposures) MDMA users over a two-year period, following an extensive baseline evaluation. The long-term goal of these studies is to provide reliable information about the extent and basis for MDMA-related acute and long-term adverse health consequences. This information will be applied to develop and test strategies to block the effects or at least minimize consequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--ANIMAL BEHAVIOR AND INFORMATICS Principal Investigator & Institution: Davies, Richard O.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: The Animal Behavioral and Informatics Core will provide support to the basic science animal projects in the Specialized Center of Research (SCOR). The core will have the following specific functions: a. To support studies of behavior for the protocols in the animal projects. This will involve studies of rest/activity, computer processing of data and ensuring that the animal being studied is normal and not a behavioral outlier. The Core staff will assist staff in the individual projects in conducting sleep (rest) deprivation studies and in sacrifice of animals. For studies involving sleep/wake recording by electroencephalographic (EEG) and electromyographic (EMG) means, the Core staffwill assist project staff in this activity and be responsible for hand scoring of all EEG/EMG records. b. To provide data base support to investigators in the SCOR using the Mouse Informatics system to allow investigators to archive and retrieve information on mouse behavior, details of animal health, method of sacrifice, tissue dissection and amount of RNA or protein obtained from microdissection techniques. c. To continue further development of the Mouse Informatics Center, and developing an Informatics Center for studies in Drosophila. d. To characterize sleep/wake patterns by EEG/EMG recording in a large sample of C57BL/6J mice during the behavioral protocols to be conducted, including the response to different durations of sleep deprivation. e. To continue participation in development of improved non-invasive ways of phenotyping mouse sleep. This will involve recording of rest/activity and analysis of digital video images with validation studies comparing the data obtained with definitive scoring of sleep by EEG/EMG methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS OF COMPENSATORY SLEEP PHENOTYPE IN MICE Principal Investigator & Institution: Dement, William C.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Increased NonREM sleep time, sleep episode duration, and EEG delta power reflect normal compensatory sleep responses (CSR) to extended wakefulness and constitute a central tenet of sleep physiology- that sleep is homeostatically regulated. In rats, catecholamine releasing stimulants (e.g., methamphetamine) also potently induce

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CSR. Wakefulness induced by selective dopamine reuptake blockers (e.g., GBR12909), however, produces no CSR, suggesting dopamine transporter involvement in sleep homeostatic mechanisms. To further investigate this possibility we will first confirm that these phenomena generalize to mice. We will then investigate stimulant interactions with sleep homeostasis in mice with null mutations of the dopamine transporter allele and in Cast/Ei mice. Our preliminary data show that Cast/Ei mice have less sleep time and attenuated compensatory sleep responses to sleep deprivation and methamphetamine-induced wakefulness relative to C57BL/6 mice. Using high throughput automated sleep scoring technology, we will investigate the involvement of the dopamine transporter in sleep homeostasis, and will begin to identify the genetic underpinnings of sleep regulatory variation between C57BL/6 and Cast/Ei mice. Four interrelated specific aims will test the hypotheses that: (1) mice (C57BL/6J) exhibit compensatory sleep responses to behavioral SD or methamphetamine-induced wakefulness, but do not exhibit compensatory sleep responses to wakefulness induced by the selective dopamine reuptake blocker GBR12909 or adenosine receptor antagonists, akin to that observed in laboratory rats; (2) the cell membrane dopamine transporter is necessary for the wakefulness-promoting effects of GBR12909, methamphetamine, caffeine and cyclopentyltheophylline.; (3) the cell membrane dopamine transporter is a functional constituent of sleep homeostasis and is therefore necessary for compensatory sleep responses to sleep deprivation (SD). We will also test the hypothesis that (4) three sleep phenotypes that differ between C57BL/6 mice and Cast/Ei mice - i.) total sleep time, ii.) compensatory sleep response to behavioral SD, and iii.) compensatory sleep response to wakefulness induced by methamphetamine treatment-- are not regulated by distinct genetic loci. Finally, we propose a set of pilot studies that will test if the cell membrane serotonin transporter is necessary for compensatory sleep responses to sleep deprivation and wakefulness induced by methamphetamine. The proposed research will advance our understanding of dopaminergic stimulant interactions with sleep homeostasis, CSR mechanisms, and genetic determinants of phenotypic variation in sleep homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINING THE GENETICS OF RESTLESS LEGS SYNDROME Principal Investigator & Institution: Earley, Christopher J.; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-MAR-2004 Summary: Restless Legs Syndrome (RLS) is a common sleep disorder especially for older adults. It is characterized by episodes of distressing sensations in the limbs, generally the legs, which are relieved by movement of the affected extremity. It is generally progressive starting at various ages but becoming both more common and more distressing for older adults. Symptoms become so severe, particularly for older adults, that in many cases activities in which movements are seriously limited and cognitive stimulation is minimal become difficult if not impossible. In addition, individuals usually have great difficulty initiating and maintaining sleep and experience severe, chronic, disabling sleep deprivation. Several reports have been published in which multiple family members are affected with RLS. Investigators have surmised that transmission of RLS follows a Mendelian autosomal dominant pattern. To date, however, no systematically ascertained family study of RLS has been published in the literature. Likewise, there are no studies of the mode of transmission for RLS. Despite this, there have been three unpublished attempts to use linkage analysis to find the

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gene(s) causing RLS. No vulnerability loci have been found. Our pilot data from 96 families of RLS patients show there is indeed a strong familial component to RLS, particularly in relatives of probands with onset earlier than 45 years of age. In these families, risk for RLS in first-degree relatives was 23.6 percent (by history as reported by the proband). This is significantly elevated over the 3.5 percent of first-degree relatives of unaffected controls found to be affected with RLS (also by history). Even within this early-onset group, there appear to be familial and non-familial groups. The Aims of the current proposal are: (1) to use direct interview methods for assessing the presence of RLS in all first- and second-degree relatives of 130 probands with RLS and compare these rates to those found in a control sample assessed with the same methodology; (2) to test the hypothesis There exists a more familial, early-onset subgroup of RS and to determine the optimum age of onset for defining such a group: and (3) to deduce the most likely mode of genetic inheritance using segregation analysis on diagnostic data of the estimated 1700 family members in the RLS sample and to perform this analysis separately for the early and late onset RLS probands. The ultimate goal of this research would be to provide reliable data from a carefully characterized family study sample with attention to evaluating age-of-onset determination of two different phenotypes as the needed basic groundwork for research to determine the genetics of RLS, a relatively common and often severely distressing disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF SLEEP HOMEOSTASIS IN THE DEVELOPING RAT Principal Investigator & Institution: Heller, Horace Craig.; Professor and Chair; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 03-JUL-1998; Project End 31-DEC-2003 Summary: (Adapted from applicant's abstract): This proposal will investigate the development of homeostatic sleep mechanisms and emergence of distinct arousal states in the neonatal rat. Arousal states cannot be identified by EEG parameters early in postnatal development, thus, arousal states in neonates are defined behaviorally as active sleep (AS) and quiet sleep (QS). AS and QS are generally considered homologous to REM and NREM sleep in adults, however, we found that EEG slow wave activity (SWA) occurs as often during AS as it does in QS at postnatal day 12 (P12). Thus, AS may not be an immature form of adult REM sleep, rather, it may be an undifferentiated state of the nervous system out of which NREM sleep emerges first and REM sleep second. We will test this hypothesis by determining when additional physiological parameters (e.g., respiratory patterns, electro-oculogram (EOG), brain and skin temperatures, and myoclonia) coalesce and form identifiable arousal states. We have developed a system for simultaneous recording of EEG, EMG, and behavioral sleep (by videotape) in neonatal rats continuously from P12 to P30. We found that adult-like responses to sleep deprivation (SD) were not present until P24; prior to that age, SD elicits increases in total sleep time (TST) without affecting the intensity or amount of SWA. From P12-P24, SWA increases progressively beyond adult levels, yet is not affected by SD. Thus, critical components of adult sleep homeostatic mechanisms must be absent prior to P24. Convergent lines of evidence support a role for adenosine in regulating SWA; however, its link to homeostatic mechanisms is unknown. We found that the adenosine A~ receptor agonist, N6-Cyclopentyladenosine (CPA), mimics the effects of SD in both adult and neonatal rats. Furthermore, CPA elicits SWA at ages (P16 and P20) when 3 h of SD have no effect on SWA. Thus, A1 receptors are present and functional but apparently not activated by SD. This proposal will investigate arousal

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state emergence, development of sleep homeostasis, and adenosinergic regulation of sleep homeostasis in neonatal rats. These studies will contribute significantly toward clinical studies on sudden infant death syndrome (SIDS) because they investigate the mechanisms by which arousal and, hence, failure to arouse, from sleep develop. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVICE TO CANCEL SECONDHAND SNORING & FOR SLEEP RESEARCH Principal Investigator & Institution: Vosburgh, Frederick; Sr Staff Fellow, Lab of Biochemistry; Nekton Research, Llc 4625 Industry Ln Durham, Nc 27713 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 30-JUN-2004 Summary: (provided by applicant): Some 25% of adults snore habitually, creating secondhand problems for those trying to sleep nearby (bed partners), frequently including chronic sleep deprivation. Sleep deprivation can impose a significant burden on health, cognition, driving ability, and social relationships. In the proposed Phase I effort, we will conduct a proof of concept (POC) test of technology for unobtrusively canceling the sound of snoring at the ears of a bed partner while permitting natural hearing of other sounds. The POC effort will comprise; 1) assembling a test system, 2) determining an adaptive situational transfer function, 3) quantifying real-time snore canceling performance of the Phase I device and algorithm and investigating sensor fusion enabling multi-transducer embodiments, and 4) working with our academic collaborator to secure IRB approval for Phase II activities involving human subjects. In Phase II, a device will be developed having consumer and sleep research applications. By selectively canceling snoring sounds, the envisioned device will enable a bed partner to sleep more and more peacefully. The envisioned device also is the basis for a new sleep research tool to study the impact of secondhand effects of snoring, as well as automating and simplifying the gathering and analyzing of breathing sound and other data useful in sleep research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIFFERENTIAL VULNERABILITY TO MORBIDITIES OF SLEEP APNEA Principal Investigator & Institution: Veasey, Sigrid C.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract) Obstructive sleep apnea (OSA) affects over 2% of the adult population in the United states and is associated with significant neurobehavioral and cardiovascular morbidities. The morbidities of OSA relate at least in part to sleep fragmentation and intermittent hypoxia, both consequences of sleeprelated collapse of the upper airway. In humans with OSA, there is significant variance in the manifestation of both the neurobehavioral and cardiovascular consequences. This variance in morbidity is only partially explained by the severity of disease. These investigators believe that vulnerability tot he morbidities of OSA is, in part, geneticallydetermined. For this proposal, they will focus on the substantial neurobehavioral consequences of sleep apnea. To begin to determine the genetic mechanisms contributing to the differential vulnerabilities, they will look separately at sleep fragmentation and chronic intermittent hypoxia (CIH) responses in inbred strains of mice. They will first expand the phenotypical response to sleep disruption to include, not only electroencephalographic changes, but also to characterize the neurobehavioral

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responses: sleepiness, changes in motor activity, learning, short and long term memory, vigilance and recovery for each of these parameters following exposure to sleep fragmentation or CIH. Responses to CIH will be characterized in the same manner. A high throughput screening algorithm will be validated against the full phenotypic responses to detect not only mutant sleep responses but mutant neurobehavioral responses characteristic of OSA. Therefore, this work provides an essential foundation for determining gene function in the susceptibility of sleepiness, impaired cognation and behavioral responses caused by obstructive sleep apnea. (End of Abstract.) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DRUG ABUSE, SLEEP AND COGNITION Principal Investigator & Institution: Hobson, J A.; Professor; Massachusetts Mental Health Institute 74 Fenwood Rd Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 30-JUN-2004 Summary: Many dysfunctional aspects of drug abuse can be understood and effectively treated only when the links between changes in levels of neuromodulators, sleep, and cognition are well described and analyzed. This proposal focuses on the cognitive effects of two drug classes, the psychostimulants (here cocaine) and the selective serotonin reuptake inhibitors or SSRIs (here paroxetine), both of which are known to potentiate the monoaminergic neuronal systems of the brain. Drawing upon our basic neurobiological knowledge and theories of sleep and cognition, we have generated specific predictions on the sleep and neuromodulatory factors mediating the cognitive effects of cocaine abuse. We will combine our validated ambulatory sleep monitor, the Nightcap, with cognitive tests that can be presented and performed on the same Macintosh computer that analyzes sleep measurements. The study of drug effects on sleep and cognition will be made considerably more economical and naturalistic by the application of this integrated ambulatory system. We plan to use this ambulatory monitoring capability at two unique research facilities, the cocaine self-administration laboratory of the Substance Use Research Center at Columbia Medical School and the Harvard Laboratory of Neurophysiology sleep laboratory, to study how sleep, monoaminergic mechanisms, and their interactions may mediate the cognitive sequelae of cocaine abuse. At the heart of this proposal is the idea that the monoaminergic drugs of abuse such as cocaine, first potentiate but then later impair the neuromodulatory dynamics of the wake-sleep cycle with ultimately deleterious effects upon cognitive functioning. We propose a series of studies which are theory-driven and which test specific hypotheses that will allow us to isolate and describe the interrelated effects of sleep and monoaminergic neuromodulators on the known negative cognitive effects of cocaine use and abstinence. In a set of seven complementary protocols, we will compare the individual and combined effects on sleep and cognitive performance of repeated cocaine administration and abstinence, administration and discontinuation of paroxetine, and REM sleep deprivation. The proposed research will answer fundamental questions regarding the cognitive benefits of sleep and how these benefits are lost when drugs are abused. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF SLEEP DEPRIVATION ON INFLAMMATORY MARKERS Principal Investigator & Institution: Wright, Kenneth P.; Associate Neuroscientist; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005

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Summary: (provided by applicant): Heart disease, vascular disease and respiratory sleep disturbance are common and complex disorders with interactions among the cardiovascular, immune, neuroendocrine, sleep and circadian systems. Because inflammation in response to acute and chronic stress responsible for tissue damage associated with disease, recent efforts to understand mechanisms underlying these disorders have lead to studies that investigated inflammatory markers. These research efforts have revealed that high plasma levels of several novel inflammatory markers-cell adhesion molecules and pro-inflammatory cytokines-predict cardiovascular morbidity and mortality. High plasma levels of these markers are also reported to be associated with the severity of sleep apnea. A variety of stressors have been reported to initiate the inflammatory response, however, whether the stress of sleep deprivation also produces higher levels of these novel inflammatory markers is unknown. The current grant application takes an integrative physiological approach to understanding health consequences of sleep deprivation by forming new collaborations between experts in vascular physiology, neuronimmunophysiology, neuroendocrinology and sleep and circadian physiology. We are requesting funds to analyze existing biological specimens that were collected under controlled laboratory conditions from healthy women and men who underwent baseline sleep and wakefulness recording and 40 hours of total sleep deprivation. We propose to test the following specific hypothesis: 0 that acute total sleep deprivation will increase circulating levels of proinflammatory cell adhesion molecules; and ii) that acute total sleep deprivation will increase circulating levels of pro-inflammatory cytokines. We also propose to measure stress hormones to determine the relationship between changes in inflammatory cell adhesion molecules, cytokines and stress hormones during sleep deprivation and during baseline sleep. Because sleep loss is an independent risk factor for heart disease and chronic sleep loss is a consequence of sleep apnea, the results of the proposed study could have important implications for understanding the molecular mechanisms underlying these disorders and their association with sleep loss. This work could also have a significant impact on our understanding of the health consequences of sleep loss, which would have implications for public health and safety. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF SHORT AND LONG NIGHTS ON THE CIRCADIAN CLOCK Principal Investigator & Institution: Eastman, Charmane I.; Professor of Psychology; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is widely recognized that humans in modern society do not get the sleep they need. This chronic sleep debt significantly degrades productivity, increases accident rates and has been linked to poor health and increased risk of death. Humans are exposed to a light dark (LD) cycle created by natural and artificial light alternating with sleep. Sleep duration determines the length of dark in the daily LD cycle. However, the effects of repeated short dark periods (short nights) on the human circadian system remain unknown. It has been proposed that mammals have a complex circadian pacemaker, consisting of an evening oscillator, that regulates the onset of melatonin secretion, and a morning oscillator, that regulates the offset of melatonin secretion. In short summer nights (longer photoperiods), the phase relationship between the evening and morning oscillators is decreased, which shortens the duration of the nocturnal melatonin profile, in turn regulating appropriate seasonal changes. Other animal work shows that the range and amplitude of the light phase

Studies

21

response curve is decreased in short nights. We propose to investigate the effects of short and long nights on the human circadian system, by keeping subjects in bed, in the dark, for either 6 or 9 hours per night. We will determine if the duration of the melatonin rhythm in dim light compresses after a history of short nights, and expands after a history of long nights, thus revealing that the circadian pacemaker has a memory of the previous night length. We will also determine if a history of short nights reduces the phase shifting response to light. Our goal is to determine the extent to which the chronic sleep debt in modern society is altering the functioning of the human circadian system. This work has important implications for the sleep deprived general population and for jet travelers and night shift workers who must phase shift their circadian rhythms in order to adjust to phase shifts in their light/dark cycle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF TREATING OBSTRUCTIVE SLEEP APNEA IN EPILEPSY Principal Investigator & Institution: Malow, Beth A.; Associate Professor; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Epilepsy affects approximately 2.5 million Americans, resulting in substantial disability. Because up to 30% of patients with epilepsy continue to have seizures despite appropriate treatment with antiepileptic medications, additional interventions to improve seizure control are needed. One approach to improving seizure control is to treat coexisting sleep disorders, such as obstructive sleep apnea. Obstructive sleep apnea (OSA) may exacerbate seizures via sleep fragmentation, sleep deprivation, or other pathophysiological processes that have not yet been determined. The investigators recently documented that OSA is common in epilepsy patients with seizures refractory to medical treatment. In addition, preliminary data in the form of retrospective case series by the investigators and others have suggested that treatment of OSA may improve seizure control. However, no prospective studies have been done to verify these findings. Proof that treating OSA is effective in reducing seizure frequency will require a multicenter Randomized Clinical Trial (RCT). This large RCT will test the hypothesis that treatment of OSA in patients with epilepsy refractory to medical treatment will reduce seizure frequency. In addition, the RCT will assess the impact of treating OSA on health-related quality of life and on daytime sleepiness, common concerns in epilepsy patients that are often attributable to antiepileptic medications or to frequent seizures rather than to a coexisting sleep disorder. The proposed aims of the Pilot Clinical Trial (PCT) are to determine critical information for the design of the RCT to allow for the testing of the above hypotheses in the RCT. In the PCT subjects 18 years and older with 4 or more seizures per month who meet survey criteria for OSA and other study criteria will be recruited at 3 different sites from epilepsy patients seen in clinical settings. A total of 60 subjects will be observed longitudinally through PSG confirmation and treatment of OSA and randomized to either therapeutic continuous positive airway pressure (CPAP) or sub-therapeutic (placebo or sham) CPAP in order to determine tolerability. Rates of adherence to therapeutic and sham CPAP and dropout rates due to antiepileptic drug changes during the treatment phase will be estimated. Specifically, the proposed PCT will: 1. Evaluate screening ranges on the Sleep Apnea scale of the Sleep Disorders Questionnaire (DA/SDQ), a survey instrument that is used to determine whether subjects are eligible for inclusion into the RCT. 2. Determine the necessity of performing two nights of PSG in patients with epilepsy. A second night of study increases the cost and may decrease

22

Sleep Deprivation

recruitment in the RCT, but may be important to include given the night-to-night variability in the PSG and the potential for seizure occurrence during recordings. The working hypothesis is that one night of PSG will be sufficient for the RCT. 3. Determine rates of adherence to therapeutic and sham CPAP, dropout rates due to antiepileptic drug changes, and response rates will provide valuable data for planning the RCT. 4. Develop quality control measures to ensure accurate and consistent data collection among sites in the RCT, including aspects related to remote data entry and standardization of performance and interpretation of PSG studies across sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXERCISE & SLEEP: A CLINICAL TRIAL IN MENOPAUSAL WOMEN Principal Investigator & Institution: Davis, Jean E.; Center for Health Research; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2006 Summary: (provided by applicant): An estimated 80 percent of the approximately 50 million postmenopausal women in the United States have complaints of disrupted sleep patterns characterized by sleep loss. Several studies show that a relative lack of estrogen interferes with optimal sleep and exogenous estrogen replacement improves sleep maintenance. However, it has been reported that less than 15 percent of postmenopausal women use estrogen replacement therapy. A growing body of evidence demonstrates that exercise improves self-reported sleep quality in postmenopausal women. The longrange goal of this research is to develop an exercise prescription that will improve the sleep of postmenopausal women. The specific objective of this research application is to determine the effects of a moderate intensity, home-based exercises program on objective sleep parameters, self-reported sleep quality, and daytime sleepiness. The central hypothesis is that a regular exercise program will improve the sleep architecture and sleep continuity patterns, subjective sleep quality, and daytime sleepiness in estrogen-deficient postmenopausal women. Employing an experimental, repeated measures, randomized treatment control group design, forty postmenopausal women who are estrogen deficient, sedentary, and have a sleep maintenance disorder will be randomly assigned to one of two conditions; an exercise group or a control group. The exercise will be home-based, moderate intensity walking with a frequency of 5 times per week and a duration of 30 minutes per session. Measurements of sleep architecture, sleep continuity, sleep quality and daytime sleepiness will be obtained at baseline and after the 16-week exercise or non-exercise period. Data on potential mediating variables of estradiol and circadian core body temperature rhythm will also be collected. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANSIM

FATTY

ACID

AND

PEPTIDE

AMIDATION--A

SHARED

Principal Investigator & Institution: Mueller, Gregory P.; Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from Applicant's Abstract ) Sleep is ubiquitous among mammals and essential for life. More than seventy types of sleep disorders chronically affect millions of Americans in all age groups. Recently, it was shown that the primary fattyacid amide, oleamide, is a mediator of sleep and may thus contribute to the genesis of sleep disorders. Oleamide accumulates in cerebral spinal fluid during sleep deprivation and induces profound motor quiescence and a sleep-like state upon administration.

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23

Primary fatty-acid amides represent a new class of receptor-active signaling molecules whose biogenesis is unknown. Understanding the pathway involved will offer targets for the therapeutic interventions for treating sleep disorders. Recently, we established in vitro that peptidylglycine-alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is able to catalyze the formation of oleamide. PAM is known for its role as the rate-limiting enzyme in the production of peptide messengers and may thus regulate the production of primary fatty-acid amides as well. The objective of this research is to elucidate the mechanisms that govern oleamide production in brain. Three specific aims are proposed for testing the hypothesis that PAM is the physiologic mediator of oleamide biosynthesis. Aim 1. Establish in a cell-free system that oleamide biosynthesis is dependent upon the actions of PAM. Cell-free models permit the direct investigation of fundamental reaction components. Subcellular fractions of N18TG2 mouse neuroblastoma cells, a line which expresses PAM and synthesizes oleamide, will be used to determine the effects of PAM inhibition on the biosynthesis of oleamide. Aim 2. Establish in cell culture that the induction of PAM during neuronal differentiation mediates an increase in oleamide production. Antisense RNA inhibition of PAM expression will be used to directly establish PAM as an integral component of the oleamide biosynthesis pathway in whole cells. Aim 3. Establish that the production of oleamide in vivo is dependent upon the action of PAM. Experiments conducted in rats will take into account the full biologic complexity of the mammalian organism. Direct measures of oleamide in brain and assessments of tissue activity for oleamide biosynthetic labeling will be used to demonstrate the extent to which inhibition of PAM in vivo impairs oleamide biosynthesis. These studies will define the physiologic role of PAM in mediating the biosynthesis of oleamide. Demonstrating that oleamide biosynthesis proceeds through PAM, or via an alternative pathway, will provide a basis for improving the diagnosis and treatment of sleep disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GERIATRIC DEPRESSION--NEUROBIOLOGY OF TREATMENT Principal Investigator & Institution: Reynolds, Charles F.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-1983; Project End 30-NOV-2003 Summary: In this revised competing renewal of MH37869-16, we propose a randomized, double-blind, placebo-controlled study to test a method for the rapid treatment of geriatric major depression and for probing treatment response variability. We hypothesize that therapeutic sleep deprivation (TSD) will accelerate response to paroxetine (PX), as compared with TSD (+ placebo) or with PX alone. In open pilot studies, we have observed a rapid response rate of 69 percent (9/13 subjects), with Hamilton depression ratings of 10 or less by 14 days, in elderly depressed patients treated with the combination of TSD (one night) and paroxetine (20 mg QHS). By contrast, in other studies of bereavement- related or recurrent major depression, we have observed rapid response rates to placebo of 15 percent, to nortriptyline of 25-32 percent, and to paroxetine alone of 26 percent, suggesting that the use of combined (TSD + medication) may double or triple the rate of rapid response as compared with placebo or drug monotherapy, respectively. With respect to treatment response variability in geriatric major depression, we hypothesize that metabolic activity in cortical areas (prefrontal cortex and ventral anterior cingulate gyrus) will decrease to normal levels in patients showing an antidepressant response to TSD and will remain decreased after recovery sleep in patients responding rapidly to antidepressant treatment. (Data from non-depressed control subjects will be collected for comparison.) By contrast, we predict

24

Sleep Deprivation

that glucose metabolism will remain elevated in non-responders and unchanged in nonresponders who may be hypometabolic at baseline. Our pilot data show a reduction in cingulate metabolism after TSD in patients but not controls; the reduction persists after successful treatment with paroxetine. We will recruit 108 elderly depressed outpatients with current major depression into a 14-day randomized, placebo-controlled, doubleblind, parallel-group study of TSD + PX, TSD + Placebo, and PX without TSD. All subjects will have pre-treatment MRI scans and twenty of 36 subjects in each treatment condition will also participate in PET studies of treatment response variability, together with 20 normal elderly control subjects. The percentage of patients meeting criteria for rapid response after 14 days of treatment in each of the three conditions will be contrasted in the intent-to-treat sample using contingency table analysis. Measures of subject expectancy, vascular risk factors, cerebral atrophy and white-matter hyperintensity, and cognitive status will be used as covariates in survival analyses of treatment response variability. Correlational analyses will be used to determine the association between changes in depression severity and alterations in regional glucose metabolic rates. Thus, this study aims to develop strategies to accelerate treatment response in geriatric major depression, to improve the early discrimination of nonresponders, to model the functional neuroanatomy of treatment response variability, and ultimately to reduce heterogeneity of treatment response in geriatric depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HANGOVER, PERFORMANCE

CONGENERS,

SLEEP

AND

OCCUPATIONAL

Principal Investigator & Institution: Howland, Jonathan; Professor and Chair; Social and Behavioral Sciences; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-JUL-2005 Summary: (provided by applicant): This competing continuation application follows up on our studies of the residual effects of heavy drinking on next-day occupational performance. These effects may represent an important, but relatively unexplored, source of injury and error in the workplace. Several studies, including our own, have indicated that even when blood alcohol concentration (BAGs) is at or near zero, occupational impairment can occur the morning after heavy drinking. These effects have been shown for driving, simulated aircraft piloting, and performance of industrial tasks. Our study proposes to increase understanding of residual effects of heavy drinking by addressing several questions. We will provide further documentation regarding these effects. We will test several hypotheses regarding the mechanism by which heavy drinking affects next-day performance. Using a placebo-controlled randomized trial, we will dose participants with placebo or with a high or low congener alcoholic beverage (to a level of 0.10 g% BAC) the night before they perform exercises on an occupational training simulator. We will monitor participants' sleep to assess sleep disturbance; collect information on hangover symptoms the morning after dosing; and collect data on participants' family history of drinking problems. We will test the following hypotheses: (1) relative to placebo, heavy drinking will degrade next-day occupational performance, and this relationship will be mediated in full or in part by quality of sleep; (2) a high congener alcoholic beverage will affect performance to a greater degree than a low congener beverage and this relationship will be mediated by severity of hangover symptoms; and (3) the residual effects of heavy drinking on next-day occupational performance will be attenuated among participants positive for a family history of alcohol problems, relative to family-history-negative participants. Our occupational

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25

model will be merchant ship navigation by maritime academy cadets. Performance will be measured using computer-based interactive ship training simulators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HERITABILITY OF SLEEP HOMEOSTASIS Principal Investigator & Institution: Kuna, Samuel T.; Associate Professor of Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: Excessive daytime sleepiness is a prevalent problem in our society associated with an increased risk of vehicular crashes and industrial accidents. Sleepiness is, in part, determined by fundamental biology relating to sleep homeostasis, i.e., the rate of accumulation of the pressure for sleep during wakefulness. A differential susceptibility to sleep deprivation is reported in normal subjects with large intra-individual differences in the degree of functional impairment produced by the same duration of sleep. Genetics are likely to play an important role in sleep homeostasis as shown by recent studies in inbred mouse strains, but whether genetics plays any role in humans and, if so, the magnitude of this role, is unknown. This proposal is based on the hypothesis that sleep homeostasis is a heritable trait in humans. Given the complexity of phenotyping to study sleep homeostasis, we propose that studying differences in the variances of the phenotype between monozygotic and dizygotic twins is the optimal approach to estimate heritability of sleep homeostasis. We will assess sleep homeostasis in 80 pairs of monozygotic and 80 pairs of dizygotic twins by quantifying the increase in delta power during recovery sleep following sleep deprivation and the increase in theta power during the period of prolonged wakefulness. Subjects will be recruited using the PennTwins Cohort, a population-based cohort of about 1,800 twin pairs. If heritability of sleep homeostasis is shown, this EEG-based phenotyping strategy could not be easily applied to the larger scale population studies that will be required to assess underlying genetic variants. Thus, part of our overall strategy is to evaluate, and potentially validate, other approaches to phenotyping that are less physiologically rigorous but are more easily applied to a larger number of subjects. Therefore, as a subsidiary goal, we will also estimate heritability of performance lapses during prolonged wakefulness as a surrogate method to assess sleep homeostasis. We will particularly determine whether the differences in the measures based on our physiological intensive phenotypes between pairs of dizygotic twins are reflected in differences in this phenotyping approach that is simpler to perform. Such a result would indicate that this simpler method could be used in larger scale population studies, and will be part of future strategies to elucidate genetic variants determining sleepiness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOMEOSTATIC REGULATION OF SLEEP IN AGING Principal Investigator & Institution: Shiromani, Priyattam J.; Associate Professor; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2004 Summary: Sleep and wakefulness are regulated for the most part by circadian and homeostatic processes. The homeostatic process is more powerful and can override circadian influences. The nature of the homeostatic process is unknown, but might be molecular in nature. Recent studies with the immediate-early gene, c-fos, have shown that this gene is expressed differentially in discrete brain regions in response to sleep

26

Sleep Deprivation

and wakefulness. These findings have led to the hypothesis that c-fos might be representative of a molecular cascade that transduces a signal involving sleep. If this cascade is compromised, as with the application of c-fos antisense (which blocks new cFos protein synthesis), or in animals lacking the c-fos gene (null c-fos), then there should be less sleep. Our recent findings support this hypothesis. The proposed studies will examine whether the diminished sleep in aging might, in part, result from a decline in cfos to AP-1 binding. Four specific aims will directly test this hypothesis. Specific aim 1 will test the hypothesis that old rats (24 months) show less sleep and slow wave activity (0.3-4.0 Hz) for a given amount of prior wakefulness compared to young rats (2 months). Rats will be kept awake (by gentle handling) for various time periods (0, 6, 12 hr) and then allowed recovery sleep. The investigators predict that young rats will have more sleep, including increased slow wave activity (0.3-4 Hz), compared to old rats. Specific aim 2 will test the hypothesis that old (24 months) rats have reduced c-Fos and AP-1 binding in wake-active populations in the basal forebrain in response to wakefulness compared to young (2 months) rats. Rats will be kept awake as in Specific aim 1 and killed following 6, 12 hr of wakefulness. Immunohistochemistry and western blot assays will qualify c-fos levels. Gel-shift assays will examine the AP-1 complex in young vs. old rats. Specific aim 3 will test the hypothesis that old rats demonstrate a reduced response to adenosine in the basal forebrain compared to young rats. Adenosine will be dialyzed in the basal forebrain in young and old rats and the increase in sleep will be measured. The investigators predict that for the same dose of adenosine, older rats will show less sleep compared to young. Specific aim 4 will test the hypothesis that adenosine induces c-fos expression and resultant AP-1 binding in the basal forebrain. The investigators predict that the c-fos induction and AP-1 binding are much stronger in young versus old rats. Their preliminary results indicate that somnogens such as adenosine induce c-Fos (measured using immunohistochemistry and on tissue slices, and via western blot analysis of basal forebrain tissue homogenate) and AP-1. 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 2002; 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

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27

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 •

Project Title: SYNDROME

HYPOCRETIN,

HISTAMINE

AND

THE

RESTLESS

LEGS

Principal Investigator & Institution: Allen, Richard P.; Assistant Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Restless Legs Syndrome (RLS) is a common sensorymotor disorders whose symptoms predominant at night and often lead to significant sleep loss and changes in one's quality of life. Rest and transiting between sleep and wake exacerbates RLS symptoms. Accordingly, alerting activities reduce while soporific ones exacerbate the symptoms. Sedating medications such as benzodiazepines, however, do not appear to exacerbate the disorder. RLS when even moderately severe profoundly disturbs sleep, reducing sleep times to 5-6 hours or less. Patients report some daytime problems with alertness and cognitive clarity but despite this reduction in sleep times untreated patients do not describe profound episodes of sleepiness that occur for normal subjects maintained on such restricted sleep schedules. There is apparently some alerting mechanism partially compensating for the sleep loss. Our recent work has found that nocturnal CSF values of hypocretin/orexin (Hcrt) are elevated in RLS patients not currently on treatment. Hcrt is almost absent in narcoleptics and serves to maintain wakefulness operating at least in part through the stimulating aspects of the histamine system. Several RLS patients on treatment with dopamine agents report some problems with sleepiness they had not previously experienced and several also report marked exacerbation of RLS symptoms by sedating anti-histamines. We have proposed that the Hcrt and histamine system activation reduces RLS symptoms for some RLS patients. DA treatment may reduce the activating benefit from this system leaving the patient vulnerable to sleepiness but also to further exacerbation of the symptoms by further reduction in this system by an anti-histamine medication. Thus, in this model, nocturnal Hcrt levels will be less for DA treated patients and antihistamine challenge provides a test discriminating those patients who have this aspect of RLS, identified in our prior work as those with the familial early-onset form of RLS. The anti-histamine challenge may therefore provide a new technique for discriminating types of RLS, possibly aiding in the diagnosis of RLS and opening up a new area of RLS research. The approach may also be extended to other DA related conditions involving sleepiness with DA treatment. This project seeks to determine if the nocturnal CSF hypocretin of RLS patients is lower when on DA treatment and to explore the development and evaluation of anti-histamine challenge for testing RLS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Sleep Deprivation

Project Title: IMPACT OF SLEEP ON FEEDING AND THE METABOLIC SYNDROME Principal Investigator & Institution: Bass, Joseph T.; Evanston Northwestern Healthcare Evanston, Il 60201 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Over the past two decades, an increased prevalence of sleep deprivation in the US has become a major public health challenge. Sleep deprivation been implicated in the epidemic of the metabolic syndrome, a condition characterized by insulin resistance, hyperlipidemia, cardiovascular disease and hypertension. Presently, 30% of the US population is overweight or obese and diabetes affects nearly 17% of persons over the age of 65. Recent clinical research indicates that sleep deprivation may pose a risk for the development of diabetes and the metabolic syndrome, however the underlying physiological and pathophysiological basis for the connection between sleep and metabolic homeostasis remains incompletely understood. This application proposes to exploit a novel experimental model of acute and chronic partial sleep deprivation in order to dissect the link between sleep loss and the metabolic syndrome. Already, we have found that chronic partial sleep loss in our animal model reproduces features of the metabolic syndrome including changes in hypothalamo-adrenal axis, decreased leptin and increased fatty acids. We have also made exciting discovery that suggest a role for alterations in the biological clock and clock regulated metabolic pathways that may lead to the metabolic syndrome. We now propose to apply the model we have developed together with molecular genetic tools to investigate the basic mechanisms that link sleep, circadian rhythms, food intake and energy homeostasis. Insight gained from these studies will provide new strategies to prevent metabolic complications associated with sleep deprivation and uncover novel metabolic targets for treatment of obesity and its co-morbidities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPACTS OF ALCOHOL / FATIGUE ON PARAMEDIC SKILLS Principal Investigator & Institution: Becker, Les R.; Pacific Institute for Res and Evaluation Calverton, Md 207053102 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2004 Summary: (Verbatim from application) A. Specific Aims Among employees in safety sensitive occupations, the two most prevalent forms of performance deficits are fatigue and alcohol related impairments, whether intoxication or hangover. The proposed research seeks to determine whether routine levels of fatigue and alcohol hangover among certified practicing Emergency Medical Technician-Paramedics (EMT-Ps) can be found to impair judgment and/or performance in such a way that patients who are reliant on the medical resuscitation and stabilization skills of EMT-Ps can be placed at unacceptable risk as a consequence of these impairments. There are currently no national standards for regulating these types of impairments for EMT-Ps, nor have the consequences of such impairments ever been systematically studied. The proposed study is important because EMT-Ps are society's front-line prehospital providers of emergency medical care, bringing Advanced Cardiac Life Support (ACLS) into America's homes and businesses. We will seek to validate a methodology and provide pilot information about specific areas of performance deficit among EMT-Ps. We will assess whether an instrumented manikin-simulator integrated with personal computerbased ACLS software can serve as a sensitive indicator, of performance impairment among licensed EMT- Ps. Depending on the findings, the results could serve to: temper

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29

concerns that typical levels of fatigue and alcohol hangover raise patient risk, warrant mounting a more comprehensive evaluation of these relationships, and/or initiate policy action that will lower risks if risks are identified. Specifically, this project aims to: o Assess EMT-P performance deficits on standard cognitive and psychomotor tasks known to be sensitive to fatigue from partial sleep deprivation as well as low blood alcohol concentration (BAC), or alcohol hangover. o Validate the sensitivity of a rescue skill-specific programmable instrumented manikin-simulator with assessment protocols known to be sensitive to fatigue and hangover, and determine the extent to which the simulation can detect areas of task-relevant impairment among EMT-Ps when they are fatigued toward the end of typically long work shifts of 24 hours, and when they are coming onto a shift following moderate alcohol use that produces hangover symptoms 6 or more hours later. o Communicate preliminary findings to the emergency medical research community and to the state and national licensing boards authorized to set policy for EMT-Ps, emergency nurses, and emergency physicians. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPORTANCE OF SLEEP & GENOTYPE IN DRUG ABUSE STUDIES Principal Investigator & Institution: Dugovic, Christine; None; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): It has been well established that both genetic background and the environment can have pronounced effects on how mice respond to drugs of abuse, including both psychostimulants and the opiates. In particular, different strains of mice respond differentially to drug treatment, and acut7e sleep deprivation alters the response to a number of drugs of abuse. However, essentially nothing is known about how the genetic background affects the response to drugs of abuse in animals with disrupted sleep. Examining the effects of sleep disruption on the response to drugs of abuse in mice with different genetic backgrounds is particularly important since one of the hallmarks of substance abuse in humans is disrupted sleep. Poor sleep, whether due to genetic or environmental causes, may in itself predispose one to abuse and drug addiction. One of the overall objectives of the proposed studies is to determine if the effects of acute sleep deprivation on the response to drugs of abuse in mice is dependent on genetic background. Since very little is known about the effects of chronic sleep loss on the response to drugs of abuse, a second overall objective will address this question and determine if the genetic background influences the effects of chronic partial sleep deprivation on the response to drugs of abuse. Six different strains of mice will be used to test hypotheses. that genetic differences in either sensitivity or sensitization of the locomotor response to either cocaine or morphine are affected by either acute or chronic partial sleep deprivation. The completion of the proposed studies is expected to not only lead to a better understanding of how genetic differences predispose mice to be more or less responsive to cocaine and/or morphine under both baseline and sleep deprivation conditions, but also will provide new insights for optimizing the genetic animal models to be used for ultimately elucidating the genetic, neurochemical and biochemical mechanisms underlying the actions of drugs of abuse. The use of these genetic animal models is expected to lead to new genetic and pharmacological strategies for the treatment of drug abuse and addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Sleep Deprivation

Project Title: INDIVIDUAL DEPRIVATION

DIFFERENCES

IN

RESPONSE

TO

SLEEP

Principal Investigator & Institution: Van Dongen, Hans P.; Research Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): The magnitude of neurobehavioral performance failure during sleep deprivation varies widely among individuals, and there are marked inter-individual differences in the structure of subsequent recovery sleep as well. Using a repeated total sleep deprivation (TSD) paradigm, the proposed project seeks to quantify the trait component of inter-individual differences in the response to sleep loss. In order to examine the malleability of the trait component, the magnitude of the trait component will also be compared with the magnitude of the response to a change in workload state. In addition, potential predictors of individual responses to sleep loss will be identified. A total of n=39 subjects will be exposed, on three consecutive occasions, to 36 hours of controlled TSD in a laboratory. Each 36-hour TSD will be followed by two 12-hour recovery sleep opportunities. Throughout the experiment, waking neurobehavioral performance will be monitored every two hours at fixed times by means of standardized behavioral tests, while baseline and recovery sleep will be studied with polysomnography (PSG) and electroencephalogram (EEG) powerspectral analysis. For each subject, two of the three TSD periods will involve moderate workload, while the other TSD period will have high (i.e. double-duration) workload, in randomized counterbalanced order. The investigation has five specific aims: (1) Quantify the magnitude and importance of inter-individual variability in neurobehavioral performance failure during TSD and the structure of subsequent recovery sleep; (2) Quantify the extent to which neurobehavioral performance failure during TSD involves a trait response and/or a state response to workload; (3) Quantify the extent to which the structure of recovery sleep following TSD involves a trait response and/or a state response to prior workload; (4) Explore the relationship between individuals' magnitude of neurobehavioral performance failure during TSD and the structure of their subsequent recovery sleep; and (5) Identify predictors of individuals' magnitude of neurobehavioral performance failure during TSD and the structure of their subsequent recovery sleep, by examining six predictor domains: baseline neurobehavioral performance, baseline sleep architecture, circadian rhythmicity, physical characteristics, psychological parameters, and demographic statistics. The results of this investigation will fill a critical gap in our understanding of inter-individual differences in the response to sleep loss, and the factors that determine these differences. The research will be relevant for the understanding, remediation and prevention of the potentially serious effects of sleep deprivation in the millions of individuals who are occasionally or routinely exposed to sleep loss due to medical condition, occupation or lifestyle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERLEUKIN 1--A PROMOTER OF SLOW WAVE SLEEP Principal Investigator & Institution: Krueger, James M.; Professor of Neurobiology; Vet & Comp Anat/Pharm/Physiol; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 30-JUN-2004 Summary: (adapted from applicant's abstract): The central hypothesis of this proposal is that interleukin-1-beta is a key regulatory component of sleep. Much data support this

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hypothesis; administration of exogenous IL-1-beta enhances non-rapid eye movement sleep (NREMS); inhibition of IL-1-beta inhibits spontaneous NREMS and NREMS induced by sleep deprivation; IL-1-beta mRNA has a diurnal rhythm in brain and increases after sleep deprivation. In Specific Aim #1, the investigators will test the specific hypothesis that the IL-1 type I receptor (IL-1RI) is necessary for IL-1-mediated changes in sleep regulation. They will use a knockout mouse lacking this receptor; preliminary data suggest that these mice sleep less than strain controls. Further, they do not respond to IL-1-beta. In Specific Aim #2 the investigators will test the hypothesis that the IL-1-beta and tumor necrosis factor-alpha (TNF) systems act in concert to regulate NREMS and are part of a larger functional gene group involved in sleep regulation. For these experiments, the investigators will use the IL--1RI knockout mouse and double knockout mouse which lacks both the IL-1RI and the TNF55-kD receptor. Specific Aim #3 tests the hypothesis that somnogenic stimuli will induce changes in specific areas of brain in the levels of one or more of the members of the IL-1 receptor antagonist will be measured using reverse transcriptase polymerase chain reaction, Northern blot analyses and RNASE protection assays. The effects of various somnogens (sleep deprivation, muramyl dipeptide and acute mild increases in ambient temperature) on the levels and distribution of these mRNAs in brain will be determined. Anticipated results will help our understanding of how the brain is organized to produce sleep. They will also help our understanding of the cellular and molecular mechanisms of sleep regulation. Knowledge of such mechanisms is likely to be a necessary step toward our understanding of sleep function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIGHT VISOR FOR TREATING JET LAG: CONTROLLED FIELD TRIAL Principal Investigator & Institution: Boulos, Ziad; Research Scientist; Bio-Brite, Inc. 4340 East West Hiwy, Ste 401 Bethesda, Md 20814 Timing: Fiscal Year 2003; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (provided by applicant): Jet lag is a syndrome of behavioral, cognitive, and physical symptoms that result when travelers are exposed to a sudden shift of the daynight cycle. These symptoms impact on alertness and performance of airline and military personnel and the safety of the traveling public. They may also exacerbate medical and psychiatric illness, and frequent flyers may face increased risk of disease. The long-term objective of this project is to develop a practical and effective treatment for jet lag using the Bio-Brite Light Visor to phase-shift circadian rhythms. Phase 1 demonstrated that the visor was effective in phase-shifting human circadian rhythms and accelerating circadian reentrainment following a westward flight across 6 time zones, but the effect on reentrainment rate was not sufficient to improve sleep, performance, or subjective measures of jet lag. Phase 2 is designed to improve the efficacy of the light treatment by implementing changes to the visor itself and to the light treatment schedule. These changes will be tested first in laboratory experiments, and then in a field study with both eastward and westward flights across 6 time zones (New York-Zurich-New York). Bright light (3000 lux) or dim red light (control) treatment will be scheduled for 3 h on the three mornings immediately preceding the eastward flight, and on the three evenings immediately following the westward flight. Subjects will also be required to avoid exposure to bright light at specific times after the eastward flight. Circadian reentrainment rates will be examined, using salivary dim light melatonin onset (DLMO) as phase reference. Other jet lag indices will include sleep quality and duration, determined from wrist actigraphic recordings and from scores on

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a subjective sleep quality questionnaire, performance on a psychomotor vigilance task, and subjective assessments of mood, daytime sleepiness, and other jet lag symptoms. Phase 2 will also include a data analysis component aimed at generating light exposure and avoidance schedules keyed to individual chronotype and to travel origin and destination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LOCUS COERULEUS ACTIVITY DURING SLEEP DEPRIVATION Principal Investigator & Institution: Doran, Scott M.; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): The project proposed in this application is designed to test how 43 hours sleep deprivation (SD) alters performance and locus coeruleus (LC) activity in rhesus monkeys engaged in a task requiring sustained and selective attention. The first goal is to validate the rhesus monkey as an animal model to explore the neurophysiology of cognition during SD. The LC is the primary source of cerebral norepinephrine and its activity is known to contribute both to attentional processes and arousal-state control. Most theoretical accounts for the impact of SD on behavior claim (or imply) that changes in LC and norepinephrine actively modulate the arousal-limited cognitive resources necessary for performance. This project will provide the first empirical test of that assumption with a design that samples performance and LC activity every 3 hours, sufficient temporal sampling to track the influence of both homeostatic and circadian pressures on performance. Human performance during SD shows increases in reaction time and error rate that is modulated by circadian phase. Sleep deprived human performance becomes highly variable, revealing both nonresponsiveness and moments of near-normal performance. To test if SD results in degraded or compensatory LC activity, baseline and task-related LC neuronal firing will be evaluated as a function of time awake during 43 hours without sleep. The ability for exogenous auditory stimulation to activate the LC and/or improve performance as time awake increases will also be tested. This project assimilates validated methods of cognitive testing in primates, electrophysiologic LC recording, and monkey sleep deprivation in an experiment designed to provide original data measuring how SD alters brain activity critical for cognition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LONGITUDINAL ADOLESCENCE

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Principal Investigator & Institution: Feinberg, Irwin; Psychiatry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 17-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Adolescence is now recognized as a period of major brain-reorganization, in addition to rapid endocrine and physical development. Among the most prominent brain changes are reductions in total sleep and a huge decline in the amplitude and abundance of the delta EEG of NREM sleep. Other brain changes in adolescence include synaptic elimination and a reduction in cortical metabolic rate. Neurodevelopmental models posit that schizophrenia may be caused or unmasked by abnormalities in these maturational processes. Daytime sleepiness emerges in adolescence, impacting mood and school performance. However, a specific withinsubjectstudy of the relation of daytime sleepiness to quantitative changes in sleep EEG

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waveforms has not been reported. There are other major gaps in our knowledge. We do not know the within-subject rates of change in the amplitude and incidence of EEG waves in delta and other frequencies, whether 'spurts' in delta decline normally occur, the shapes of the age curves, their relation to age vs. pubertal stage, and the extent of individual and gender differences. Our research aims to fill these gaps by studying sleep longitudinally in 2 age cohorts (ages 9-13 and 12-16 years) during the period of most rapid change. Baseline and extended sleep will be studied twice/yr for 4 years. EEG waveforms will be quantified with FFT-spectral and period amplitude analyses (the 2 most widely used computer methods) and with visual sleep stage scoring. Sleepiness will be assessed with the MSLT and behavioral ratings and mood will be systematically evaluated at each time point. The proposed research will help fill major gaps in our knowledge of one of the most pronounced maturational changes of the human brain, It will also test specific hypotheses regarding the : correlates of these changes. The data we acquire could shed light on concomitant brain changes, leading to the identification of new biological relationships. Our studies will also provide benchmark data for neurodevelopmental studies in psychiatrically ill adolescents and 'at-risk' population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MDMA CONSEQUENCES

NEUROTOXICITY

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Principal Investigator & Institution: Ricaurte, George A.; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 31-MAR-2007 Summary: (Adapted from applicant's abstract): The 3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy'') is an illicit amphetamine analog that is increasing in popularity in the United States and abroad. In addition to its abuse potential, MDMA is well documented as a potent and selective serotonin neurotoxin in animals. A growing body of evidence indicates that human MDMA users are also susceptible to MDMA-induced serotonin neurotoxicity. Although functional sequelae of MDMA-induced serotonin neurotoxicity appear to be subtle, a number of laboratories have documented abnormalities in memory and other cognitive processes in MDMA users compared to matched control groups. Since it is known that neurons involved in cognitive processes decrease with aging (e.g., catecholaminergic and cholinergic neurons), there is concern that MDMA users may be at risk for developing clinically significant cognitive abnormalities as they age. The overall goal of this revised competing renewal application is to determine if pharmacological and physiological challenges that are intended to simulate selected features of aging (i.e., loss of catecholaminergic/cholinergic function and/or sleep continuity) can be used to better detect and characterize possible detrimental effects of MDMA neurotoxicity upon cognitive processes in humans. The hypothesis to be tested is that MDMA-induced brain serotonergic injury will render MDMA users more susceptible to cognitive deficits associated with disruption of catecholaminergic and cholinergic neurotransmission and sleep continuity. The Specific Aims of the project are: 1) To determine whether or not MDMA users, compared to matched controls, are more susceptible to the disruptive effects of the catecholamine synthesis inhibitor, alpha-methyl-para-tyrosine (AMPE), on cognitive processes; V To determine if MDMA users, compared to matched controls, are more susceptible to the disruptive effects of the cholinergic antagonist, scopolamine, on cognitive processes; 3) To determine whether or not sleep deprivation, a naturalistic physiological challenge that is known to lead to deficits in cognition (and which is common in elderly populations), produces more profound effects on cognition in

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MDMA users compared to matched controls; and 4) To determine whether there is a relationship between cognitive deficits in MDMA users and the level of CSF 5hydroxyindoleacetic acid, a validated measure of MDMA-induced brain serotonin neurotoxicity. The proposed studies hold promise for improving our understanding of the functional consequences of MDMA-induced serotonin neurotoxicity in humans, and should advance knowledge regarding the role of brain serotonin and other neurotransmitter systems in cognition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF DIFFERENTIAL SLEEPINESS IN SLEEP APNEA Principal Investigator & Institution: Weaver, Terri E.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: The purpose of this proposal is to explore potential operating mechanisms in the differential sleepiness observed in patients with equivalent degrees of obstructive sleep apnea (OSA). Within a given level of disease severity, i.e., number of respiratory disturbances during sleep, inter-individual differences, or differential vulnerability to sleepiness, have been noted in both subjectively measured and objectively measured daytime sleepiness. The reason for this phenomenon remains unclear. Critical to the management of patients with OSA is the understanding of mechanisms associated with the development of daytime sleepiness. We hypothesize that the variance in daytime sleepiness (EDS)will have a substantial trait component in addition to state-related factors among patients with equivalent levels of OSA severity. To systematically identify sources of EDS variance in sleepy and non-sleepy OSA patients, the specific aims of this study will determine: 1) state-specific variance related to sleep duration, obesity and fat distribution, specific comorbidities, and use of certain medications; 2) mis-estimation of severity of sleep disordered breathing from night-to-night variability in respiratory disturbances; 3) underlying trait associated with differential vulnerability to the sleepiness-producing effects of OSA. Using actigraphy and diaries to document sleep duration and both objective and subjective evaluations of sleepiness, Protocol A will classify 260 newly diagnosed OSA subjects as sleepy vs. non-sleepy and will document inter-individual differences in sleepiness among patients with similar disease severity caused by sleep history, obesity and fat distribution, specific comorbidities, and use of certain medications. Controlling for the variance identified in Protocol A, Protocol B will determine the degree to which inter-individual differences in sleepiness in 180 untreated OSA subjects with similar disease severity is a consequence of night-to-night variability in the occurrence of sleep disordered breathing documented by 7 consecutive nights of home sleep studies. Such night-to-night variability would reduce the reliability of single night determinations of apnea severity. Finally, in Protocol C we will determine if inter-individual differences in sleepiness remain after accounting for the variance explained by the clinical factors identified in Protocol A and the variance explained by mis-estimation of severity of sleep disordered breathing documented in Protocol B. In Protocol C, 60 patients (30 sleepy, 30 non-sleepy) will be matched on initial apnea severity and a set of a priori sleepiness factors will undergo 38 hrs of sleep deprivation in a laboratory to determine the existence of an underlying trait for daytime sleepiness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS UNDERLYING THE COGNITIVE FUNCTION OF SLEEP Principal Investigator & Institution: Datta, Subimal; Professor; Psychiatry; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-DEC-2000; Project End 30-JUN-2005 Summary: The long-term objective of this application is to identify the cellular mechanisms underlying the cognitive function of sleep. Specifically, the goal is to investigate what role brainstem rapid eye movement (REM) sleep generating structures play in sleep-dependent learning in the rat. Clarifying the mechanisms of sleepdependent learning and memory will move the field of cognitive research closer to the development of effective treatments for cognitive deficiencies associated with sleep disorders. The central hypothesis of this proposal is that activation of phasic P-wave generating cells in the dorsal part of the nucleus subcoeruleus is critical for sleepdependent learning and memory processing. From this hypothesis, four testable questions have been generated: 1. After learning task training, does supplementary activation of the P-wave generator enhance information processing efficiency, resulting in improved learning? Immediately after a session of two-way active avoidance test trials, the P-wave generator will be directly activated by a discrete microinjection of carbachol. The effect of this supplementary activation will be examined in retest trials after a six hour period of undisturbed sleep. 2. Does the activation of the P-wave generator during REM sleep enhance a physiological process of memorization which naturally occurs during post-learning sleep? The procedure for testing this question is the same as that of question 1, except that these rats are REM sleep deprived for the six hour period between test and retest trials. 3. Does the elimination of cells in the P- wave generator attenuate learning abilities in post-sleep retest trials? P-wave generating cells will be directly eliminated by a discrete microinjection of kainic acid. The retest performance of these P-wave generating cell lesioned rats will be compared with that of the sham lesioned rats. 4. Is the increased density of P-waves during post-learning REM sleep due to the activation of P-wave generating cells? P-waves and single cell unitary activity of P-wave generating cells will be simultaneously recorded in freely moving rats after a session of learning trials. This proposal addresses at the mechanistic level, the general question, what is the function of sleep? and also promises to further sleepdependent cognitive research in the direction toward treatments for cognitive impairments associated with jet lag, shift work, sleep deprivation and brainstem degenerative disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MELATONIN RANDOMIZED TRIAL FOR INSOMNIA IN THE ELDERLY Principal Investigator & Institution: Gooneratne, Nalaka S.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Chronic insomnia affects up to 35% of the elderly. It can significantly impair quality of life and daytime functioning. Currently, most medical therapy for insomnia involves sedative-hypnotic agents that may lead to dependence, withdrawal side effects and reduced efficacy after extended periods of use. A growing body of work has suggested that melatonin, a neurohormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, the primary circadian pacemaker, may play a role in mediating insomnia. Ongoing research at the University of

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Pennsylvania in 180 elderly insomnia patients has found statistically significant evidence of a decreased sleep efficiency in low melatonin insomniacs. Thus, melatonin production is impaired in a subgroup of elderly insomnia patients and this may contribute to their insomnia. However, melatonin treatment trials in elderly insomniacs have been equivocal. These studies have had serious methodologic limitations including inadequate sample size (Type II error), lack of objective measures of sleep or daytime functioning, and no placebo control arm. This has raised many questions such as whether melatonin deficiency is a marker of insomnia or, instead, a contributing factor and whether increased doses are needed to recreate the higher levels seen in the cerebrospinal fluid compartment. In addition, melatonin is widely used as an over-thecounter sleeping aid with litre true insight into its effectiveness/safety, especially in older adults. To address the primary hypothesis that melatonin can treat insomnia in melatonin-deficient elderly, the principal investigator proposes conducting a large randomized, double-blind clinical trial comparing low dose melatonin (0.4 mg), high dose melatonin (4.0 mg) and placebo in a well-defined group of elderly insomniacs with low melatonin levels (189 total subjects). The specific aims are to 1) evaluate the effectiveness of melatonin and 2) assess the daytime consequences and safety of melatonin treatment in this population. Intention-to-treat analysis will compare low dose melatonin, high dose melatonin, and placebo on objective and subjective parameters of sleep and daytime function. This protocol will extend well beyond the research done to date by rigorously testing the role of targeted melatonin replacement therapy as an effective treatment for insomnia in the elderly and by evaluating the safety profile of melatonin with a particular focus on daytime functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEMORY CONSOLIDATION AND SLEEP Principal Investigator & Institution: Hellman, Kevin M.; Neurology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: The goal of our research is to identify the neural mechanisms by which sleep enables memory consolidation. Sleep regulates many physiological processes and impairment of sleep is seen in many diseases that impair memory: Alzheimer's disease, Parkinson's disease, depression and sleep apnea. Many studies have demonstrated sleep deprivation following learning will impair memory. We will use behavioral experiments, electrophysiology and molecular biology to deduce the neural mechanisms responsible for sleep alterations after fear conditioning. We will use fear conditioning as a learning paradigm to because it is a single-trial task with a defined time course of memory consolidation. After fear conditioning, we have discovered that mice have a period of increased arousal followed by increased sleep three hours following fear conditioning. We have also seen changes in thalamo-cortical (delta) and hippocampal (theta) oscillations associated with sleep. During the period of arousal there is a decrease is both delta and theta oscillations, but during the following 2 hour sleep period there is an increase in delta and theta oscillations. We believe these change in sleep activity are essential to memory consolidation because when we sleep deprive mice following fear conditioning long-term memory consolidation is impaired. In Specific Aim 1 we will identify changes in sleep after fear conditioning. In Specific Aim 2 we will identify alterations in gene transcription and protein synthesis during sleep after fear conditioning. In Specific Aim 3 we will examine the role of the cAMP/PKA/CREB signaling during sleep following fear conditioning in transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MONOAMINERGIC NEUROPSYCHIATRY

FUNCTION

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Principal Investigator & Institution: Smith, Gwenn S.; Associate Professor; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Applicant's abstract): An important therapeutic issue in neuropsychiatric disease, particularly in geriatric patients, is the variability in treatment response and the inability to predict treatment outcome. Decreased monoaminergic responsiveness may be a potential neurobiologic mechanism underlying treatment resistance across several neuropsychiatric disorders. The overarching theme of the candidate's funded research in AD, schizophrenia and geriatric depression is that decreased monoaminergic responsiveness is related to treatment resistance. To evaluate monoaminergic function in vivo, the candidate has developed methods using Positron Emission Tomography (PET) imaging, radiotracers for neurotransmitter receptors and pharmacologic challenges. This application of PET methodology represents the most direct, noninvasive and quantitative method of measuring neurotransmitter activity in the living human brain. The PET studies performed thus far have consistently demonstrated substantial between subject variability in monoamine responsiveness in normal controls and in patients. Variability of monoamine responsiveness has been observed also in pharmacologic challenge studies using behavioral and neuroendocrine outcome measures. The goals of this Independent Scientist Award are to obtain training in methods complementary to brain imaging techniques that will enable the candidate to better interpret the variability in monoaminergic responsiveness observed in the PET data. The goals of the training experience are to incorporate genetic markers of monoamine receptor and transporter alleles and polysomnographic methods into her existing research program and to obtain training in the neuroanatomy of cholinergic and monoaminergic interactions and neuroimaging in affective disorders. The research plan is conducted within the framework of three funded studies to use PET to investigate 1) serotonin-dopamine interactions in schizophrenia; 2) cholinergic modulation of monoamine function in Alzheimer's Disease; and 3) the effects of sleep deprivation and antidepressant treatment on cerebral glucose metabolism in geriatric depression. These studies are designed to relate alterations in monoamine responsiveness to subsequent therapeutic response. The long term goal of the candidate's research is to understand the neurobiologic substrates of treatment resistance in neurodegenerative disorders and to use the genetic, polysomnographic and imaging data to predict the course of pharmacotherapy. The Independent Scientist Award will enable the candidate to firmly focus her research in the area of geriatric neuropsychiatry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL GENE EXPRESSION IN SLEEP DEPRIVATION AND RECOVERY Principal Investigator & Institution: Kilduff, Thomas S.; Senior Director; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2003; Project Start 30-SEP-1997; Project End 30-JUN-2007 Summary: (provided by applicant): The function of sleep and the biochemical nature of the restorative process that occurs during sleep are among the great mysteries of neuroscience. Experimental observations confirm the common experience that sleep deprivation (SD) leads to sleepiness and that restricted sleep time imposes a sleep "debt" which ultimately must be "repaid" by sleep extension. The hypothesis that underlies our

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studies is that the homeostatic sleep-related "Process S" is biochemical in nature and the sleep-dependent restorative process involves macromolecular synthesis that can be detected at the RNA level. Consistent with this idea, during the previous funding period we have identified several genes whose expression is increased during sleep after SD. In the current application, we propose to determine expression of these and other genes at multiple times during recovery sleep after SD. Recent studies have determined that, although the time constant for the decay of Process S (taud) is highly conserved, the time constant for the increase of Process S (taui; referred to as sleep "need") varies considerably among mouse strains. Therefore, we will compare the neural gene expression profile in three strains of mice that exhibit large differences in the buildup of sleep need to identify mRNAs whose expression may increase in parallel with sleep need. Building on the neural gene expression database that we have established in the current funding period, we will extend our microarray studies to pharmacologically induced sleep and compare the patterns of gene expression induced by clinically effective hypnotic agents to that observed during normal sleep. These experiments may determine whether a final common pathway for sleep induction can be identified. Last, building on a model of hypothalamic and preoptic area involvement in sleep regulation that has emerged over the last few years, we will test the hypothesis that clinically used hypnotics are effective in sleep induction through changing the functional activity of brain nuclei known to be sleep- or wake-active. These experiments should provide insights into the biochemical process occurring during wakefulness that predisposes to sleepiness as well as the restorative i process that occurs during sleep itself. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBEHAVIORAL EFFECTS OF PARTIAL SLEEP DEPRIVATION Principal Investigator & Institution: Dinges, David F.; Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-DEC-2003 Summary: The role of sleep in maintaining healthy, optimal waking functions, is compromised by sleep loss from illness, aging, pain, depression, and life-style. The single most pervasive form of sleep loss experienced by millions of persons for either medical or lifestyle reasons is partial sleep deprivation (PSD). This project seeks to determine how waking neurobehavioral functions sensitive to sleepiness are affected by chronic PSD. A basic unresolved question is the amount and timing of chronic PSD at which alertness and waking function are compromised. This research is specifically aimed at establishing the nature and time course (across hours and days) of deficits engendered by chronic sleep restriction, and the extent to which they reflect an interaction between the homeostatic drive for sleep and the endogenous circadian pacemaker. The project involves the first systematic laboratory controlled experiments on the effects of 14 days of PSD on neurobehavioral and physiological functions. A randomized controlled trial will be performed in which three PSD dosages (4hr, 6 hr, 8 hr, per day) are placed at three different circadian phases (time-in-bed offset at 0330hr, 1130hr, 1930hr), thereby yielding nine conditions, each of which exposes a different range of the circadian cycle to waking neurobehavioral assessment. A total of 180 healthy adults will be studied (n=20 per condition) in the laboratory for 20 days each, during which time they will undergo 14 days of sleep restriction. Assessments will be made of key outcome variables including psychomotor vigilance lapses, cognitive functions, working memory, EEG alertness, subjective sleepiness, and mood. The results of this research will provide much-needed information on current issues of intense theoretical and applied concern including particular relevance to current public policy

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needs for data regarding the number of hours personnel in safety-sensitive occupations should have available each work day for sleep, and the number of consecutive days they should be allowed to work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGY OF SLEEP APNEA IN AGING Principal Investigator & Institution: Carley, David W.; Professor; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: (Applicant's abstract): Sleep apnea syndrome affects at least 3 percent - 5 percent of the adult population in this country and available data suggest that significant morbidity and mortality result from this disorder. It is now well established that the prevalence of sleep-related apnea is dramatically elevated in the elderly with recent estimates ranging from 28 percent - 67 percent for elderly males and from 20 percent - 54 percent for elderly females. However, the mechanisms underlying the age related increase in apnea genesis remain poorly understood. This uncertainly stems in part from a paucity of appropriate animal models to study spontaneous apneas in all stages of sleep. Rapid eye movement (REM) sleep is associated with apneas, reductions in respiratory and upper airway motor outputs, and increased variability of respiration, heart rate and blood pressure. We present novel preliminary evidence suggesting that increased apnea expression with aging results from dysregulation of brainstem respiratory control systems by brainstem phasic events (BPE) in the elderly. Pontogeniculo-occipital (PGO) waves are a close marker of BPE and are closely associated with cardio- respiratory changes, including apnea. The overall goals of this proposal are to (i) investigate the neural mechanisms by which BPE influence apnea genesis, and (ii) establish the importance of these mechanisms to the age-related increase in apnea. To achieve these goals, we will combine descriptive and interventional human studies with invasive central nervous system measurements and manipulations in rats using a model of sleep-related respiratory instability which we have characterized. We will focus our attention on the pedunculopontine tegmental nucleus (PPT), the putative site of the burst generator responsible brainstem phasic events detectable as PGO waves. We will manipulate BPE expression in two directions: 1) we will augment expression by acoustic stimulation and sleep deprivation in man and rat and by microinjection of cholinergic agonists into PPT in the rat; and 2) we will reduce expression by electrolytic lesions of the PPT in the rat. These manipulations in old and young patients, controls, and rats will provide a comprehensive approach to define the mechanisms and importance of brainstem phasic event-induced respiratory instability in aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROCHEMICAL REGULATION OF CIRCADIAN TIMING Principal Investigator & Institution: Rea, Michael A.; Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): In mammals, the sleep and circadian systems are intimately coupled and mutually essential for the proper coordination of physiological processes and behavior. The circadian clock located in the suprachiasmatic nucleus (SCN) provides for the temporal organization of sleep by promoting alertness during periods of high homeostatic sleep drive. In turn, the circadian program of sleep organization is synchronized to environmental rhythms through periodic adjustments

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of the phase and period of the circadian clock by ambient light. The neuroanatomical and neurophysiological mechanisms responsible for the imposition of circadian organization on the sleep process are only beginning to be understood. Furthermore, no mechanism has yet been described through which sleep-related processes might influence circadian timing. The current proposal seeks to delineate such a mechanism. The purine nucleoside, adenosine, has been implicated as a key component of the homeostatic sleep mechanism. Adenosine accumulates in the basal forebrain cholinergic area during sustained wakefulness, where it has been shown to promote sleep through an adenosine A1 receptor-dependent mechanism. Systemic administration of an adenosine A1 receptor agonist attenuates the magnitude of light-induced phase adjustments of the SCN circadian clock. We propose that adenosine provides information to the circadian clock regarding the state of fatigue of the organism, resulting in an altered response to light-induced phase adjustments. In the current proposal, we will test the hypothesis that increased adenosine production in the SCN region during sustained wakefulness attenuates light-induced adjustments in circadian phase by interacting with presynaptic A1 receptors located on RHT nerve terminals to reduce the release of glutamate. This work will reveal a novel and potentially important aspect of sleep and circadian regulation in mammals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROCHEMICAL SUBSTRATES OF SLEEP HOMEOSTASIS Principal Investigator & Institution: Dorsey, Cynthia M.; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Difficulty initiating/maintaining sleep afflicts up to 30% of the population, yet the neurochemical processes associated with sleep and sleep disturbances have not been clearly identified. A better understanding of EEG slow-wave activity and its role in recovery from sleep loss could be invaluable in elucidating the homeostatic sleep mechanism and shedding light on how to treat disturbed sleep. Further, sleep disturbances contribute to relapse to drug use and such efforts might help address this serious public health problem. The purpose of the study is to identify neurochemical markers of sleep mechanism in an intact and an impaired system, by evaluating changes in brain chemistry produced by disrupted sleep. In response to RFAHL-01-009, "Interrelationship between sleep and heart, lung, and blood diseases" we propose two experiments. In the first, polysomnography (PSG) and phosphorous magnetic resonance spectroscopic imaging (31P MRSI) will be collected at baseline, after sleep deprivation, and after recovery sleep in controls and in methadone-maintained subjects. Measures will be repeated at 1 and 3 months to determine if the effects persist. In the second experiment, PSG and 31P MRSI data will be collected from unmedicated cocaine-dependent and opiate-dependent subjects during acute withdrawal and at 1 and 3 months post withdrawal. As the abstinence profile for sleep disturbance differs in these groups (hypersomnia vs insomnia, respectively) this experiment will help delineate the conditions under which altered brain bioenergenics exist. 31P MRSI can be used to measure global and focal changes in high energy phosphate alpha-,gamma,beta-NTP (ATP). Our pilot data showed significant increases in beta-NTP and decreases in phospholipid catabolite production after recovery following sleep deprivation in control subjects. 31P MRS changes have been observed in chronic opiate-dependent individuals at baseline, but have not been evaluated during sleep. Chronic sleep disturbances have been reported in opiate abusers and methadone-maintained patients and the homeostatic sleep mechanisms may be impaired in chronic opiate abuse. We

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hypothesize that methadone-maintained subjects will have decreased beta-NTP and will exhibit smaller slow wave sleep rebound and a more modest or no increase in beta-NTP after recovery. Further, the neurochemical response to sleep deprivation in these subjects will approach that of controls over time b-NTP will increase during cocaine withdrawal and decrease during opiate withdrawal, reflecting their differential effects on sleep during this time. Collectively, these studies may identify neurochemical markers for the recovery function of sleep, thus enhancing our understanding pf basic sleep mechanisms and potentially leading to new and improved treatments for sleep disturbances in both the substance-abusing and general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROENDOCRINE ABNORMALITIES INDUCED BY SLEEP DEPRIVATIO Principal Investigator & Institution: Everson, Carol A.; Associate Professor; Neurology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): Sleep is a vital biological process necessary to maintain cognitive ability and physical health. Profound sleep disturbance/deprivation in humans is nearly always associated with disease, and sleep deprivation in patients is considered a high risk factor for mortality. In animal models of sleep deprivation, morbidity is associated with septicemia subsequent to a constellation of neuroendocrine changes, most notably hypothyroxinemia. Preliminary data have shown that neuroendocrine abnormalities extend to deficiencies in growth hormone (GH) and prolactin (PRL), and have the potential to explain most of the pathology induced by sleep deprivation. There is strong evidence that the neuroendocrine changes are centrally mediated. The following three specific aims are intended to test the main hypothesis that sleep deprivation results in hypothalamic dysfunction: Aim 1: To determine whether centrally-mediated hypothyroxinemia is due to deficient proTRH expression and TRH secretion in sleep-deprived animals. Proposed studies will determine whether TRH mRNA expression in the paraventricular nucleus and TRH content in the median eminence are suppressed and unresponsive to low T4, indicating impaired thyroid hormone regulation at the level of the hypothalamus. The pathway of T3 feedback to PVN neurons will be examined to determine the degree of up-regulation in response to low T4. Potential TRH responsiveness of thyrotrophs will be assessed by evaluating TRH receptor mRNA expression in the pituitary. Aim 2: To identify regulatory mechanisms responsible for reduced growth hormone and prolactin levels in sleep-deprived rats. Proposed studies will examine the regulation of PRL and GH in individual rats during the course of sleep deprivation by studying stimulatory and inhibitory mechanisms and response that could be responsible for the deficiency at the hypothalamic and pituitary levels. Aim 3: To delineate effects of sleep deprivation on thyroid hormone processing in the brain. Low thyroid hormone concentrations in sleep-deprived rats imply decreased T4 availability for import to the brain and ensuing centrally-mediated dysfunction common to the clinical hypothyroid state. Proposed studies will examine the content and regulation of iodothyronines in the sleep deprived brain. These studies will delineate the abnormalities in brain endocrine regulation resulting from sleep deprivation and determine the mechanisms responsible for peripheral endocrine changes that underlie its associated systemic pathologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROPEPTIDE CORTISTATIN AND SLEEP Principal Investigator & Institution: De Lecea, Luis; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 30-JUN-2007 Summary: (provided by applicant): Cortistatin is a neuropeptide that has a strong similarity to somatostatin and selectively induces slow wave sleep, presumably by antagonizing the effects of the neurotransmitter acetylcholine on cortical excitability. Preprocortistatin is exclusively expressed in a subset of cortical and hippocampal interneurons that utilize GABA as their neurotransmitter. These features and others make cortistatin a sleep factor that may have a major role in cortical synchronization and the maintenance of slow wave sleep. During the period of the grant entitled "Neuropeptide cortistatin and sleep," three animal models have been generated, cortistatin-overexpressing transgenic mice, cortistatin systemic knock-out and cortistatin conditional knock-out mice. In this competitive renewal, cortistatin-deficient (cst ko) mice will be studied using anatomical, behavioral, electrophysiological and molecular methods. Cst ko mice will be analyzed for anatomical and developmental abnormalities. Since the activity of cortical interneurons is important for the maintenance of slow wave sleep electrophysiological measures of excitability will be recorded in hippocampal slices of cst ko mice. The consequences of cortistatin mis-expression on sleep- and circadian-related processes will be studied in mice with null mutations in the cortistatin and somatostatin genes. Finally, the molecular consequences of cortistatin and somatostatin deficiency will be studied using oligonucleotide-based microarrays and alternatively with differential display methods. Completion of this proposal will unambiguously address the role of cortistatin and somatostatin peptides in sleep regulation, delineate their signaling pathway and analyze possible cross-talk or genetic compensation, which may yield therapeutic applications and a better understanding of human sleep disorders in which cortical activity is affected. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NIGHT SHIFT WORKERS AND HORMONE LEVELS IN WOMEN Principal Investigator & Institution: Davis, Scott; Professor of Epidemiology; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 11-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The primary objective of the proposed study is to determine whether working at night is associated with decreased levels of the nocturnal urinary concentration of 6-sulphatoxymelatonin, and increased levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol in a sample of healthy women of reproductive age. Secondarily, this study is designed to investigate whether urinary levels of melatonin are lower and levels of reproductive hormones are higher during daytime sleep relative to nighttime sleep among women who work at night. Approximately 200 nurses who work the night shift exclusively and 150 nurses who work the day shift exclusively will be recruited as volunteers in the Seattle metropolitan area. Eligible participants must be between the ages of 20 and 40, employed for at least 20 hours/week, resident of King or Snohomish County, do not take oral contraceptives or other hormone preparations, and have no personal history of breast cancer. In addition, the night shift nurses must normally sleep at night during off days. This study will employ a design which allows for both between-subject comparisons of night shift v. day shift workers, and within-subject comparisons during day sleep v. night sleep among the night shift workers. Participation will span two months. In the first month

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the study will evaluate menstrual cycle regularity, determine the day of ovulation using a commercial kit, conduct a personal interview regarding employment and reproductive history, assess the participant's ability to adjust to shift work, and collect a blood sample. In the second month urine sample collections will be scheduled during both work and sleep periods, and will take place in the early to mid-luteal phase of each participant's cycle. Sleep patterns will be measured via actigraphy during the sleep periods corresponding to urine collection. Oral temperature data will be collected during waketime in the night shift workers to determine temperature amplitude. Information will be collected on factors which may be related to the hormones under study, such as alcohol consumption, medication use, and hours of daylight during sample collection. Urine samples will be assayed for the primary urinary metabolite of melatonin, 6sulphatoxymelatonin, and levels of LH, FSH, and estradiol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPTIMIZATION OF AN IMPLANT TO TREAT SLEEP DISORDERS Principal Investigator & Institution: Metzger, Anja K.; Restore Medical, Inc. 2800 Patton Rd Saint Paul, Mn 55113 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 30-NOV-2003 Summary: (provided by applicant): Snoring and obstructive sleep apnea are part of sleep disordered breathing (SDB) continuum. Beginning with mild snoring, this continuum progresses to obstructive sleep apnea in those most severely afflicted. SDB can result in sleep deprivation leading to daytime sleepiness, posing a risk for work place accidents, especially for those operating heavy machinery or motor vehicles. The long-term consequences of sleep-disordered breathing consist of an increased risk of high blood pressure, heart disease, and stroke. Current treatments to reduce snoring can be very painful and remain effective for only a short period of time before follow-up treatment is required. Pi Medical proposes a simple, relatively painless, placement of an implant to stiffen the soft palate, thereby, eliminating the vibrations known as snoring. The implantable device overcomes the disadvantages of current treatments by placing a permanent implant into the soft palate using a very simple procedure. The potential to use the implants to treat obstructive sleep apnea syndrome (OSAS) also exists. OSAS is characterized by intermittent closure of the pharyngeal airway during sleep resulting in episodes of hypoxemia and sleep disruption. Currently there are no treatments aimed specifically to treat the collapse of the pharyngeal walls. An effective treatment would be aimed at reducing the compliance of the pharyngeal walls; this would reduce their ability to collapse and alleviate upper airway obstruction without interfering with normal functions. The purpose of this research is to evaluate methods to maximize tissue ingrowth and fibrotic response to the implants with the expectation that this will increase the total stiffening effect of the implant and result in an implant that provides adequate properties to alter the compliance of the airway structures to 1) positively effect snoring levels or 2) prevent pharyngeal wall collapse associated with obstructive sleep apnea without affecting the normal function of the pharyngeal walls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OUTCOMES ADOLESCENTS

OF

SLEEP

DISORDERED

BREATHING

IN

Principal Investigator & Institution: Redline, Susan S.; Professor of Pediatrics, Medicine & Epid; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): In children, unrecognized Sleep Disordered Breathing (SDB) may significantly contribute to learning and behavioral problems, and predispose to the development of cardiovascular problems. Adolescents may be predisposed to SDB because of weight gain or sleep restriction. However, the prevalence and impact of SDB in teenagers have not been systematically studied. Over the last 3 years, we have studied a unique cohort of 907 children (41% minority), ages 8-11, many who have been under observation since age 3 years. Our physiological and neuropsychological measurements provide fundamental data regarding the prevalence of SDB and risk factors for SDB in pre-pubertal children. Preliminary analyses indicate that children with snoring or SDB perform more poorly on a number of tests of cognitive function, and have more behavioral morbidity than do other children. We propose extending this study to assess the morbidity of SDB in adolescents (ages 13-16 years), addressing the extent to which SDB in childhood impacts behavior, cognitive functions, and neuro-endocrine responses important in the pathogenesis of cardiovascular disease or diabetes. We hypothesize that the effects of sleep fragmentation, reduced slow wave sleep and sleep-associated intermittent hypoxemia may lead to deficits in executive functions, insulin sensitivity, and abnormalities in the somatotropic axis. We also will quantify the impact of putative risk factors on adolescent SDB, including race/ethnicity, overweight, small pharyngeal size, prematurity, familial SDB, and SDB at ages 8-11 years. For efficiency, we will perform stratified sampling of 250 children from this cohort (125 with habitual snoring or sleep apnea at ages 8-11 yrs., and 125 children randomly selected from the remaining cohort, frequency matched by gender, term, and race). Children will undergo overnight stateof-the-art-sleep monitoring, a glucose tolerance test, acoustic rhino-pharnygometry, anthropometry, spirometry, blood pressure, and a focused battery of neuropsychological and behavioral assessments. Specimens for biomarkers and potential confounders (e.g, measures of puberty and thyroid status) will be collected, some both before and after sleep. First-degree relatives also will undergo sleep studies and relatives and children will have DNA collected for future studies. This proposal provides the opportunity to characterize the prevalence and morbidity of SDB in a wellcharacterized population-based sample, including a large proportion of minority and preterm adolescents who appeared to be at high risk for SDB at younger ages, and may be at increased risk for SDB-associated chronic morbidities, and poorer cognitive development. Comprehensive data collection and statistical analyses will permit identification of potential pathophysiological mechanisms for, and effects of, SDB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREDICTORS OF ADVERSE METABOLIC EFFECTS OF SLEEP LOSS Principal Investigator & Institution: Spiegel, Karine; Free University of Brussels 50 Ave Franklin Roosevelt Brussels, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Chronic sleep loss, obesity and sleep-disordered breathing (SDB) are increasingly common in industrialized countries. Sleep curtailment in healthy young lean adults results in the development of components of the metabolic syndrome, including reduced glucose tolerance and/or insulin resistance, elevated evening cortisol levels, increased cardiac sympatho-vagal balance, and a risk of weight gain resulting from reduced leptin levels and increased hunger and appetite. The studies proposed in the present application build on novel findings from our group that indicate that obese individuals may be more at risk for further weight gain than lean

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individuals in conditions of sleep loss, and that individuals levels of slow wave activity (SWA), a stable trait-dependent marker of deep sleep, may predict subjective vulnerability to sleep loss, and are also likely to predict the severity of adverse metabolic and cardiovascular consequences of sleep loss. We therefore propose to characterize sleep architecture, autonomic nervous system (ANS) activity, and biomarkers of the metabolic syndrome in three groups of middle aged (35-50 years old) subjects studied while they follow their usual sleep habits as well as during 4 days of sleep restriction and sleep extension, presented in randomized order in a cross-over design. The three groups of subjects will be healthy lean men and women, gender-matched individuals who are obese, and gender-matched individuals who are obese and also suffer from SDB. The specific aims are: 1. To test the hypothesis that baseline levels of SWA are lower in obese adults than in lean controls, and are even lower in obese subjects with SDB, and examine correlations between levels of SWA and sleep duration, ANS activity and biomarkers of the metabolic syndrome. 2. To test the hypothesis that sleep restriction, as compared to sleep extension, has adverse effects on biomarkers of the metabolic syndrome in lean adults, obese adults, and obese adults with SDB. 3. To test the hypothesis that the adverse impact of partial sleep loss on components of the metabolic syndrome is more important for obese adults than in lean adults, and more severe in obese adults with SDB than in those without SDB. This project capitalizes on our experience with human studies of "sleep debt" and on our extensive expertise in assessment of ANS activity to evaluate the role of the ANS as a mediator of the adverse health effects of chronic sleep loss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDUCING STRESS /SLEEP DISTURBANCES IN CAREGIVERS OF AD Principal Investigator & Institution: Hall, Martica; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: The stress of caregiving is associated with a number of adverse health outcomes including psychiatric morbidity, immune system dysregulation, increased susceptibility to illness and disease, and increased risk for mortality. Sleep complaints are common among caregivers, and stress-related sleep disruptions may signal vulnerability to, or play a causal role in, the adverse health consequences of caregiving. The general aim of this revised study is to test the efficacy of an intervention designed to reduce stress and improve sleep in a sample of spousal careqivers of patients with Alzheimer Disease (AD). The intervention will be compared to an attention-only control condition. Specific aims of this study are: 1. To characterize stress-related sleep disruptions in spousal caregivers of AD patients. 2. To test the short-term efficacy of a stress management+healthy sleep practices (SM+HSP) intervention for improving sleep and health outcomes in AD caregivers. 3. To test the durability of SM+HSP in AD caregivers. The study will include 60 spousal caregivers of AD patients who will be randomly assigned to one of two treatment conditions. The SM+HSP intervention will consist of eight weekly in-home sessions that will focus on information support, skills training, affective self-management, and healthy sleep practices. Individually, these components have been shown to be efficacious for reducing stress or improving subjective sleep complaints in AD caregivers. The control condition will include eight weekly in-home sessions which will focus on diet and food intake. Treatment integrity will be monitored by audiotape recordings. The program project measures battery (Agebat) and additional measures specific to caregiving will be administered at four

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time points: prior to randomization, immediately post-intervention, and at 6- and 12month follow-up visits. Project -specific data will be used to evaluate treatment efficacy and relationships among caregiver stress and sleep. Relationships among stress, sleep, and health will be more fully evaluated using program-wide data collected in Project 15. Our program-wide aim is: to characterize the impact of stress-related sleep disruptions on health in older adults, including AD caregivers, recent widows/widowers, patients with insomnia in primary care settings, and healthy elders above the age of 75 years. The main hypotheses to be tested within the individual project are that the stress of caregiving has a detrimental effect on sleep and that stressrelated sleep disruptions, in turn, negatively impact health and well-being. It is hypothesized that, relative to the attention-only control condition, the active intervention (SM+HSP) will result in improvements in sleep and subsequent improvements in health and well-being. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION WAKEFULNESS

OF

CHAT

EXPRESSION

DURING

SLEEP-

Principal Investigator & Institution: Greco, Mary A.; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: The neuronal circuitry underlying sleep-wakefulness is beginning to be understood. Changes in the release of neurotransmitters across sleep-wakefulness are well documented. The intracellular events associated with the activity of these neurons across sleep-wakefulness, however, are not clear. The available evidence suggests that the transcriptional activation of genes occurs during sleep, indicating that changes in protein and mRNA expression are likely to occur during sleep as well as waking states. The function of sleep is not known. One hypothesis is that sleep serves to replenish biomolecules depleted during waking. If sleep serves such a function, The intracellular environment of brain centers involved in sleep- wakefulness will support biosynthesis. The main hypothesis of this proposal is that changes in the expression of key enzymes associated with neurotransmitter synthesis occur sleep- wakefulness to maintain neurotransmitter stores. To test this hypothesis, the expression of choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine will be examined. Specific aim 1 will test the hypothesis that chat mRNA is increased during sleep. In these experiments, mRNA levels will be examined during waking, non-REM and REM sleep states that occur across a 24-hour period. Specific aim 2 tests the hypothesis that protein activity and/or protein levels vary across individual sleep bouts over a 24-hour period. Specific aims 3 and 4 will test the hypothesis that sleep loss effects mRNA expression (Specific aim 3) and protein expression (Specific aim 4). In these experiments, the reversibility of the effects of sleep loss will also be monitored during the recovery sleep period. Sleep disorders affect approximately 70 million Americans with associated costs estimated at billions of dollars in lost revenue per year. By identifying how sleep might replenish key enzymes in neurotransmitter synthesis, we will advance our knowledge of sleep. The experiments proposed are the first steps in the identification of cellular mechanisms effecting acetylcholine synthesis across sleep-wakefulness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REM SLEEP DEPRIVATION, HYPOXIA, AND HIPPOCAMPAL FUNCTION Principal Investigator & Institution: Gozal, David A.; Professor and Vice-Chair for Research; Pediatrics; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 30-JUN-2004 Summary: Obstructive sleep apnea syndrome (OSAS) is a frequent condition affecting up to 5 percent of the population, and is characterized by repeated episodes of hypoxia and recurrent EEG/behavioral arousal, particularly during REM sleep. When untreated, OSAS is associated with significant neurocognitive morbidities such as excessive daytime sleepiness and diminished intellectual performance, attention span, learning and vigilance. However, the relative contributions of REM sleep deprivation (REMSD) and episodic hypoxia to OSAS-associated neurocognitive dysfunction remain unclear. To test the hypothesis that REM sleep deprivation and episodic hypoxia affect learning and memory in an additive fashion, four major specific aims will be examined in a young adult rat model as follows: (1) The acquisition and retention of Morris water maze task paradigms will be assessed in conscious 55-60-day old male rats after either 4day REMSD using the inverted flower pot technique, 14-day episodic daytime hypoxia (EHYP), or the combination thereof (REMSD-EHYP); (2) The effect of such exposure paradigms on long-term potentiation (LTP) within the CA1 region of the hippocampus will be examined using neurophysiological extracellular recordings of the in vitro hippocampal slice preparation; (3) Changes in ionotropic glutamate receptor distribution and in apoptosis within the hippocampal formation and neocortex will be determined using immunohistochemical and wester blot approaches in naive and maze trained animals following REMSD, EHYP, or both; (4) Alterations in early gene induction (c-fos) elicited by maze learning procedures will be further assessed in the hippocampus of REMSD, EHYP, and REMSD-EHYP by immunohistochemistry and AP1 electromobility shift assays. These e xperiments will extend our understanding on potential mechanisms and interactions underlying the decreased performance that occurs in particular neurocognitive functions of untreated OSAS patients. In this context, REMSD, EHYP, or both would lead to either up-regulation or down-regulation of specific ionotropic glutamate receptor complexes, induce apoptosis, and thereby modify early gene activation patterns associated with learning or retention of newly learned tasks. Such alterations in receptor-signal transduction pathways could also lead to both short- and long- term changes in neuronal excitability and synaptic transmission within brain regions with important and defined roles in memory formation and learning such as the hippocampus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEX DIFFERENCES IN MOOD DISORDERS Principal Investigator & Institution: Cartwright, Rosalind D.; Professor; RushPresbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-MAR-2004 Summary: (provided by applicant) This study tests a putative mood-regulatory function of REM sleep and or dreaming in depressed males and females. Previous work in this laboratory has shown that those depressed who remain untreated are more likely to remit over a one year period if they demonstrate increased REM pressure (higher eye movement density, more frequent REM episodes, and reduced REM latency), and if they demonstrate higher proportions of negative affect dreams in the first half of the

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night than in the last (a 'working through' of affect within the night). Thirty-two depressed volunteers with equal numbers of males and females are tested for mood before and after each of two nights of laboratory-monitored sleep on three occasions over a five month period. REM sleep will be interrupted to retrieve dream reports every second night. This manipulation also increases REM pressure. Data will be analyzed for differences between sex groups for 1). the effects of REM pressure (between sleep through and REM interrupted nights) 2). Dream affect change (between half nights), 3). dream-like quality of reports, and 4). problem focus in dream content on overnight mood regulation and on remission of depression. Findings will contribute to an understanding of REM sleep and dream function, and the sex difference in rates of depression. This study will also have implications for the treatment of depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP AND NEURAL PLASTICITY IN DEVELOPING NEOCORTEX Principal Investigator & Institution: Frank, Marcos G.; Physiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-DEC-2002 Summary: (provided by applicant): This application proposes neurophysiological studies to determine the role of sleep in the development and plasticity of the mammalian visual cortex. Our previous research has demonstrated a role for sleep in the plasticity elicited by monocular deprivation (MD) during the critical period for visual development in the cat. These findings suggest an important role for sleep in the developing brain and have important implications for our understanding of cortical plasticity, learning and memory, and the function of sleep. In addition to providing insights into these areas of study, the proposed studies should provide important information regarding the role of sleep in human neural development, and the longterm consequences of sleep loss on the developing brain. The overall goal of the proposed studies is to determine the contribution of rapid-eye-movement (REM) and nonREM sleep to two forms of developmental plasticity in visual cortex. Short periods of MD during the cat critical period trigger rapid remodeling of thalamocortical circuits in primary visual cortex in favor of the open eye. A related form of synaptic plasticity, elicited by opening the previously closed eye and closing the previously open eye (reverse-MD) can produce recovery of cortical function. We will first determine the contribution of each sleep state to the cortical plasticity elicited by MD. We will then determine if the effects of sleep on cortical plasticity are mediated by the patterns of neural activity present in REM or nonREM sleep. We will then investigate the role of sleep in the cortical plasticity elicited by reverse-MD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP AND NOCTURNAL ASTHMA IN YOUTH Principal Investigator & Institution: Kieckhefer, Gail M.; Family and Child Nursing; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term objective of this research is to expand knowledge about nocturnal asthma in youth so early identification of symptoms and targeted treatment are possible. The specific aims of this research are to: test model of the mechanisms by which sleep or sleep related changes in autonomic system functioning and inflammation trigger nocturnal asthma symptoms, sleep disruption, and cause daytime tiredness in youth; compare objective and subjective indicators of

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quantity and quality of sleep between youth with varying degree of nighttime asthma symptoms and youth not having asthma; and determine which subjective and objective measures or combination of measures of sleep are the best predictors of daytime tiredness and activity limitations in children having asthma. The study uses a 2 group (asthma/no asthma) experimental design. Fifty children (half with asthma) will participate with a parent. Parent and child will provide historical information on sleep and breathing problems at night; 7 days of diary report on the child s sleep, respiratory symptoms, pulmonary function and daytime tiredness and activity limitation due to breathing problems. The child will wear a wristwatch like band to monitor their movements during 7 nights of sleep at home and then come into the sleep laboratory or more in-depth monitoring of sleep and pulmonary function. The child's usual bedtime will be used during the first Bedtime will be delayed by 4 hours the second night to intensify sleep to in-laboratory sleep monitoring determine if this intensification has a detrimental effect on the child's pulmonary function. Innovative, non-invasive markers will be used to evaluate changes in autonomic system function (heart rate variability) and pulmonary inflammation (exhaled nitric oxide) during the in-laboratory sleep nights. Examining this data in the context of the adult data already reported in the literature should allow identification of possible development differences in the influence of sleep on nocturnal asthma symptom expression that would be worthy of further study. The information gained is critical to practicing health care providers who are working to quell rising ast morbidity particularly in ethnic minority children living in poverty. 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 2002; 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

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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 •

Project Title: SLEEP DEPRIVATION AND 5-HT AUTOREGULATORY PROCESSES Principal Investigator & Institution: Lopez, Faustino; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 12-FEB-2001; Project End 31-JAN-2006 Summary: (applicant's abstract): This Mentored Clinical Scientist Developmental Award application includes a program of career developmental and research training for the applicant, Faustino Lopez-Rodriguez, M.D, Ph.D. The ultimate goal of the applicant is to develop as an independent investigator in examining the neurobiology of antidepressant mechanisms of action. The career developmental and research plan are designed to allow the applicant to reach this goal. The applicant intends to supplement his background in electrophysiology with techniques in neurochemistry (microdialysis of biogenic monoamines in behaving animals and high performance liquid chromatography) and molecular biology, which he plans to acquire during the Award period. The applicant intends to apply his expertise in sleep physiology to study the neurobiological mechanisms underlying the antidepressant effects induced by sleep deprivation. In this proposal, and as a first step in an overall research program, the applicant will concentrate on the effects of sleep deprivation on serotonin (5-HT) activity. His specific aims are as follows. 1) Sleep deprivation induces changes in 5-HT release in forebrain structures and is accompanied by sustained high levels of 5-HT in the raphe. 2) Sleep deprivation changes the activity of 5-HT1A and 5-HT1B autoreceptors. The applicant hypothesizes that sleep deprivation blocks the effects of 5HT1A and/or 5HT1B agonists on 5-HT release, as well as the amounts and synthesis of 5-HT1A and 5-HT1B autoreceptors. 3) Sleep deprivation modifies the synthesis of 5-HT. In addition to studying the overall effect on 5-HT synthesis, the applicant will determine the effect of sleep deprivation on brain tryptophan concentration, gene expression of tryptophan hydroxylase (TPH, the rate-limiting enzyme in the biosynthetic pathway), and TPH activity. A better understanding of these sleep deprivation-related changes has the potential to advance our knowledge, both in sleep physiology and antidepressant mechanisms of action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DEPRIVATION AND ALCOHOL EFFECTS IN MARIJUANA USERS Principal Investigator & Institution: Liguori, Anthony; Assistant Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003

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Summary: (Applicant's Abstract) Marijuana and alcohol are drugs that contribute to automobile accidents when used separately and in combination. A further danger to adults who drive after late-night drug use is sleep deprivation. While many postaccident blood analyses have implicated marijuana and alcohol, no controlled empirical studies have quantified the combined behavioral and subjective effects of sleep deprivation with either marijuana or marijuana-alcohol combinations. The novelty of this project is its use of controlled Sleep Laboratory measurements, a driving simulator, computerized body sway measurement, a test of divided attention, and self-report mood scales to assess the various ways sleep deprivation and alcohol impair a driver who uses marijuana. The project has three specific aims. The first aim is to quantify how alcohol alters the effects of marijuana on mood, equilibrium, attention, and simulated automobile driving. The second aim is to quantify how partial sleep deprivation alters the effects of marijuana on these measures. The third aim is to quantify the effects of sleep deprivation on marijuana-alcohol combinations. Three studies using randomized placebo controlled designs are proposed. In each study, subjects will smoke a marijuana cigarette (0, 1.77, or 3.95% delta 9 THC) in two or three separate conditions. Study 1 will manipulate a concurrent dose of alcohol (0.0, 0.5, or 0.8 g/kg). Study 2 will manipulate pre-session sleep hours (8 vs. 3). Study 3 will add the expectation and experience of alcohol to the conditions of Study 2, with each subject drinking a dose of alcohol (0.0, 0.5, or 0.8 g/kg) before testing. The dependent variables to be studied include 1) body sway as measured by computerized dynamic posturography, 2) subjective effects scales (Profile of Mood States and Visual Analog Scales), 3) the Stroop Color Test of divided attention, and 4) brake latency within the driving simulator. By clarifying the separate and combined effects of marijuana, alcohol, and sleep deprivation on these ecologically valid measures, the results will contribute to the prevention of drug-related highway fatalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP DEPRIVATION, EEG, & FUNCTIONAL MRI IN DEPRESSION Principal Investigator & Institution: Clark, Camellia P.; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 20-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant's abstract): The objective of this 5-year Mentored Clinical Scientist Development Award for Cametlia Clark, M.D. is to develop the candidate's expertise in functional magnetic resonance imaging (MRI) while building on her previous skills in neuroimaging and sleep research. This goal will be accomplished through a carefully designed training plan involving didactic courses and mentorship by experts (at and outside UCSD) in basic neuroscience, structural MRI, functional MRI (fMRI) physics, sleep and affective disorders research, and statistics as well as intensive instruction in fMRI research in a setting featuring state-of-the-art scanners, innovative pulse sequences (particularly perfusion-weighted), and the first fMRI studies utilizing sleep deprivation (SD) to study cognitive function in normal subjects (published recently in Nature and NeuroReport. This training program will enable Dr. Clark to complete the transition to independent investigator and provide the foundation for a long-term research program utilizing fMRI and polysomnography to investigate brain function in affective disorders. The research plan utilizes one night of partial SD (PSD), an excellent model of antidepressant treatment which is fast-acting, and does not require medications. The applicants hypothesize: I) depressed responders' baseline perfusion signal intensity in the ventral anterior cingulate (BA 25 and ventral 24) / medial prefrontal cortical (BA 32) areas will be greater than that of nonresponders and controls;

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2) following PSD, perfusion in the ventral anterior cingulate (BA 25 and ventral 24) / medial prefrontal cortical (BA 32 and 10) areas will significantly decrease in responders only. The applicants will also look for between-groups and within-groups differences in other regions where functional abnormalities have been reported in depression, including (but not limited to) dorsal anterior cingulate, dorsolateral prefrontal cortices, medial frontal cortices, amygdala, hippocampus, thalamus, and basal ganglia. Finally, the applicants will look for possible between-groups structural MRJ differences, which could potentially confound fMRI analyses. FMRI perfusion data will be analyzed by the analysis of variance algorithm in AFNI (Analysis of Functional Neural Images) software. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP DISORDERED BREATHING AND GLUCOSE REGULATION Principal Investigator & Institution: Polotsky, Vsevolod Y.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: provided by applicant): Sleep Disordered Breathing (SDB) and type 2 diabetes mellitus are serious health problems associated with obesity. Recent epidemiological studies have shown that SDB may be linked to insulin resistance and glucose regulation, independent of obesity. However, the mechanisms by which SDB may affect glucose and insulin regulation are unknown. Putatively, the intermittent hypoxia (IH) and sleep fragmentation of SDB may impact on glucose regulation. Hypoxia could affect the insulin-glucose axis through upregulation of hypoxia-inducible factor- I alpha (HIF- 1alpha) which activates expression of glucose transporters, resulting in decreased blood glucose levels. On the other hand, sleep fragmentation could lead to stress and activation of insulin counter-regulatory hormones, such as cortisol and epinephrine, resulting in increased blood glucose levels. In our Preliminary Data we show that IH causes a biphasic response consisting of a decrease in blood glucose levels after one week followed by a rise in blood glucose after three weeks of exposure. Furthermore, the absence of the metabolic hormone leptin resulted in a more pronounced hyperglycemic phase in response to IH compared to wildtype mice. Our major hypothesis is that SDB causes biphasic changes in glucose homeostasis. The early decrease in blood glucose is due to hypoxic activation of HIF- 1alpha and upregulation of glucose transporters. The late increase in blood glucose is due to sleep fragmentation activating insulin counter-regulatory hormones, and this effect is exacerbated by leptin deficiency. In order to test our hypotheses we will utilize a mouse model of IH as well as a mouse model of SDB. We will use wildtype mice, with and without dietary obesity, as well as leptin deficient ob/ob mice and transgenic HIF- 1alpha mice. In Specific Aim I we will determine-nine the time course of changes in blood glucose, serum insulin, insulin counterregulatory hormones, and tissue glucose transporters during IH in lean and obese mice. In Specific Aim 2 we will separate the effects of IH and sleep fragmentation on glucose regulation. In Specific Aim I we will specifically examine the role of HIF- 1alpha and leptin in glucose responses to IH using transgenic mice. Thus, this study will examine mechanistically how SDB affects glucose regulation, which could have a significant impact on both fields of SDB and diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DISRUPTION IN NEW PARENTS: AN INTERVENTION TRIAL Principal Investigator & Institution: Lee, Kathryn A.; Professor and Livingston Chair; Family Health Care Nursing; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2003 Summary: This longitudinal study utilizes a stress and coping framework to test an intervention to minimize the stress of sleep disruption and thereby improve the outcomes for new parents after the birth of their first infant. Data from the principal investigator's previous research and knowledge of sleep hygiene principles provide the basis for this proposal. The primary aim is to test the effects of an environmentalbehavioral intervention on sleep, fatigue, well-being, and marital satisfaction. This intervention will be introduced prior to delivery to allow the couple to adapt to the equipment involved in the intervention. Hypotheses will be tested using repeated measures analysis of variance to determine mean group differences. It is expected that: 1) The experimental group of new mothers (n=60) and new fathers (n=60) will have significantly fewer awakenings, and higher sleep maintenance than control mothers (n=60) and fathers (n=60) at all 4 postpartum time points; 2) The experimental group of new mothers and new fathers will report significantly lower fatigue and higher wellbeing and marital satisfaction compared to controls at all four postpartum time points (2, 4, 8, and 12 weeks). A secondary aim is to describe the success by which new parents incorporate this intervention into their lifestyle and evaluate its feasibility for other firsttime parents. Level of satisfaction with the intervention package will be ascertained for both experimental fathers and experimental mothers before and after mothers return to work. Results from this study will be useful in developing an educational intervention package for distribution to all adults preparing for parenthood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DISTURBANCE IN MARIJUANA WITHDRAWAL Principal Investigator & Institution: Bolla, Karen I.; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Marijuana is the most widely used illicit drug in the United States. Heavy marijuana users who attempt to stop using marijuana frequently report sleep disturbance, restlessness, nervousness/anxiety, increased aggression, and appetite changes. We believe that sleep disturbance may pose an enormous hindrance to successful cessation of heavy marijuana use. Surprisingly, despite several subjective reports of sleep disturbance in newly abstinent heavy marijuana users, there have been no studies using objective polysomnographic (PSG) measures validating these subjective reports. Therefore, this study is highly significant and very innovative because in addition to collecting subjective measures of withdrawal symptoms, we will obtain repeated objective measures of sleep architecture using standard PSG procedures. We will determine if there are objective polysomnographic findings of sleep disturbance in marijuana users (N=16) abstaining from drug use for 14 days in an inpatient setting at NIDA-IRP. Sixteen non-drug using controls, will be included for comparison and matched to the marijuana group on age, gender, and sleep-wake pattern. The control group will reside on our GCRC for 3 days. Baseline sleep-wake patterns will be estimated in both groups with actigraphy and sleep log recordings for 5 days prior to withdrawal/admission. The marijuana users will be transferred from NIDA-IRP to the

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GCRC core sleep lab for PSG recording. We will obtain PSG sleep measures of sleep onset, sleep maintenance, and restlessness at three separate times over 14 days of withdrawal and compare these to PSG measures obtained from the comparison group. Moreover, changes over time will be determined in the marijuana users. We will also determine if marijuana users have delayed sleep phase syndrome, a possible cause of sleep onset difficulty, by measuring dim light melatonin. The long-term goal of this research is to determine if heavy marijuana use is associated with objective sleep abnormalities as measured by polysomnographic procedures. Such findings could lead to new treatments for alleviating the unpleasant symptoms of marijuana withdrawal. For example, delayed sleep phase syndrome, one cause of insomnia, could be treated with light therapy, the same treatment used successfully for treating seasonal affective disorder. New treatments for alleviating the unpleasant symptoms of marijuana withdrawal would likely increase the number of heavy marijuana users who successfully complete treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP FRAGMENTATION EFFECTS ON MURINE CII-INDUCED AR Principal Investigator & Institution: Postlethwaite, Arnold E.; Medicine; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Patients with rheumatoid arthritis (RA) and other chronic arthritides have partial chronic sleep deprivation (PCSD) possibly related to the pain and inflammation associated with their condition. It is unknown what effect PCSD has on the immune and non-immune mediated arthritic processes of RA and related arthritides. Recent work in laboratory animals and humans indicates that sleep deprivation produces immune-related consequences. The overall goal of this study is to induce chronic, partial sleep fragmentation in DBA/1 lac mice during the evolution of the primary immune resonse to ovalbumin (OVA) in mice and during the evolution of type II collagen (CII)-induced arthritis (CIA) in this same mouse strain. We will test the hypothesis that PCSD in DBA/1 lac mice will result in alterations in the immune response to OVA and severity of arthritis. The approach will Ibe to tailor an experimental chronic sleep deprivation appartus to fit the mouse, develop and lvalidate a computerized program, implement experimental conditions of selective partial sleep Ideprivation in a consistent and reliable manner, and then assess the effects of PCSD on immune Iresponse to OVA and arthritis induced by immunization with CII. The following specific aims will address this hypothesis: Specific Aim 1: Assess sleep patterns in arthritic mice; Specific Aim 2: Conduct total sleep deprivation in mice to produce partially sleep-deprived mice; Specific Aim 3: Determine whether chronic partial sleep deprived DBA/1 lac mice immunized with OVA develop altered immunity to OVA; and Specific Aim 4: Determine whether chronic partial sleep-deprived DBA/1 lac mice immunized with CII have alterations in the incidence and/or severity of arthritis. Results of the study will provide a basis for submitting an R01 grant to explore mechanisms by which partial sleep deprivation in DBA/1 lac mice alter the immune response to antigen and arthritis development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP MECHANISMS IN CHILDREN: ROLE OF METABOLISM Principal Investigator & Institution: Haddad, Gabriel G.; Pediatrics; Yeshiva University 500 W 185Th St New York, Ny 10033

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Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Sleep and the neurobiological mechanisms controlling sleep/wakefulness have been an enigma in spite of important recent advances in the field. Although it is well known now that sleep affects a variety of systems, including the cardio-respiratory, endocrine and autonomic systems, we still do not understand why we sleep and the mechanisms that control sleep. For example, we do not have a good understanding of the mechanisms that induce or maintain sleep or those mechanisms that are activated with sleep deprivation. One of the potentially important areas that have started to develop is the role of brain metabolism in sleep. Although metabolic studies during sleep have been done in the past few decades, new developments in brain imaging and spectroscopy have made it possible only recently to examine the importance of metabolism in sleep research. Furthermore, and of major interest, is the growing evidence that glia play a critical role in maintaining neuronal function through metabolic support through glutamate re-cycling and possibly by providing neurons with substrates for glucose oxidation. Glycogen is found only in glia and hence glycogen metabolism, the glutamine-glutamate cycling and glucose oxidation involve links between glia and neurons. Hence, in order to understand sleep and its mechanisms, it becomes important to study the functional integrity and coupling of neurons and glia and their relationship as a function of state. For conceptual reasons and in order not to complicate the experimental matrix, we will focus this application on stage III-IV sleep and will address our questions comparing this sleep stage to a well defined state of wakefulness. Furthermore, since previous studies have taught us about sleep and its mechanisms by studying sleep deprivation, we will, in a subset of our children, address the same questions after sleep deprivation. Our specific hypotheses are as follows: 1. Stage IV sleep has a lower metabolic requirement and a lower glutamate turnover rate (tricarboxylic acid cycle rate) in both neurons and glia, as compared to wakefulness. 2. As compared to wakefulness, sleep stage IV is characterized by a lower rate of brain neuronal glutamate release and glial glutamate uptake in children; this reduced glutamate/glutamine cycling during this sleep stage in brain of children is prevented by sleep deprivation. 3. Brain glycogen content increases during the course of sleep in children and sleep deprivation markedly lowers glycogen content. Our long term aims are a) to better understand sleep and b) to be able to better understand diseases that afflict children or adult and which impact on their sleep or diseases that are sleep-related that impact on other functions including neurocognitive, cardiovascular or behavioral functions. As seen from reviewing the state-of-the-art above, there are major gaps in our knowledge and this application focuses on a number of these gaps. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP MEMORY: A MOLECULAR AND GENETIC ANALYSIS Principal Investigator & Institution: Abel, Edwin G.; Assistant Professor; Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: The goal of our research is to elucidate the molecular machinery underlying sleep and to define the role of sleep in the consolidation of long-term memory. Sleep is involved in many physiological processes, and disturbances in sleep are a hallmark of many diseases, including neurodegenerative disorders such as Alzheimer's disease, in which memory deficits are prominent. An understanding of the relation between sleep dysfunction and memory loss may help us to better define the pathophysiology of these diseases. We are interested in bridging past behavioral studies, which have shown that

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sleep is needed for the consolidation of memory, with current knowledge about the molecular mechanisms underlying memory storage. Mice are an ideal system with which to explore the relationship between sleep and memory consolidation. Our recent work has used genetic and pharmacological approaches in mice to demonstrate that protein kinase A (PKA) activity is critically important for long-term memory storage. There are striking parallels between the effects of sleep deprivation and the effects of pharmacological manipulation of the PKA signaling pathway on the consolidation of memory. Both sleep deprivation and inhibition of PKA disrupt the consolidation of memory only at discrete times following training and these times vary depending on the strength of the training protocol. Based on this, we propose to examine the role of the cAMP/PKA/CREB signaling pathway in the behavioral effects of sleep deprivation on hippocampus-dependent tasks in mice. In Specific Aim 1, we will determine the effects of total sleep deprivation as well as rapid eye movement (REM) and non-REM (NREM) sleep deprivation on contextual fear conditioning, a single-trial hippocampusdependent learning task in mice. Specific Aim 2 will focus on biochemical and molecular assays to directly measure changes in PKA activity and phospho-CREB levels in the hippocampus after sleep deprivation and contextual fear conditioning. Specific Aim 3 will investigate the hypothesis that sleep may modulate memory storage through the prominent cholinergic flux to the hippocampus that occurs during REM sleep. In Specific Aim 4, we will examine sleep architecture in mice with genetic alterations in the cAMP/PKA/CREB signaling pathway to test the hypothesis that memory consolidation deficits in these mice are due to altered patterns of sleep. The broad-based experimental design of this proposal, using genetic, pharmacological, electrophysiological and behavioral approaches, will bring us closer to an understanding of the molecular and biochemical processes underlying sleep and enable us to define the role that sleep plays in memory consolidation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP/DOPAMINE PHENOTYPES IN GENETICALLY DISTINCT MICE Principal Investigator & Institution: Rye, David B.; Associate Professor; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (adapted from the applicants' absract) One poorly understood neuromodulator of state is the mesostriatal dopamine (DA) system, which not only promotes motivation/reward and movement, but also arousal (viz., wakefulness). Conversely, DA blockade and interruption of mesostriatal pathways slows movement and promotes sleepiness. The details of mesostriatal DA's effects upon wake/sleep rhythms, and sleep architecture, and the cellular and subcellular substrates involved remain poorly defined. Circadian and homeostatic wake/sleep factors affect mesostriatal circuit plasticity, but their functional import is also undefined. Mice with genetic deletions of the dopamine transporter (DAT-/-), their heterozygotes (DAT+/-), wild type littermates, the pure C57BL/6 and S129/sv strains from which the transgenics derive, and the DBA/2 inbred strain with known under expression of mesostriatal D2 receptors afford a means to probe DA's role in state control, and to account for genetic variation in wake/sleep phenotypes. Aim #1 proposes to characterize 24-hour motor activity patterns in relation to sleep/wake architecture in these mice. Motor hyperactivity in DAT -/- and DAT +/- during the subjective night yields to hypoactivity during subjective day suggesting a sleep/wake reversal in the face of chronically elevated synaptic DA (preliminary data). The mechanisms underlying a homeostatic

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sleep drive powerful enough to overcome chronic DA elevations - if indeed sleep attends the observed hypoactivity - may reside in other proteins involved in mesostriatal DA transmission. Aim #2 therefore proposes to measure traditional DA markers, and molecularly defined D1 receptor, DAT and vesicular monoamine transporter (vMAT2) expression across 24-hours in limbic and motor striatal circuits to enhance interpretation of Aim #1 findings. Aim #3 investigates the effects of prolonged wakefulness induced by physical means, bupropion (a DAT blocker), and caffeine (an adenosine receptor blocker), on the mesostriatal DA system in these same mice. The investigators postulate that these transgenic and inbred mice will exhibit unique circadian rhythms of proteins mediating DA neurotransmission and unique responses of these proteins to prolonged wakefulness that may be treatment modality specific, much the same way that depressives differ in their response to REM-sleep deprivation, and narcoleptics differ from depressives in their REM-sleep responses to DAT blockade. Taken together, the findings will advance an understanding of how state might modulate the course and treatment of insomnia, depression, and neuropsychiatric diseases whose pathophysiologies are rooted in DA sensitive basal ganglia circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOCIALIZATION OF INFANTS' STATE, ATTENTION, & AFFECT Principal Investigator & Institution: Super, Charles M.; None; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, Ct 06269 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 30-JUN-2004 Summary: The long-term goal of this study is to expand our knowledge of the early development of arousal, attentional and affective behaviors, especially as they are shaped by culturally specific caretaking practices. The research design will capitalize on a natural experiment in parallel communities in the Netherlands and the USA. Two groups of infants (60 in each community) will be followed from shortly after birth until age 2 years. Assessment procedures include parent interviews, diaries, and actigraph recordings of daily activities and rest, samples of salivary cortisol at specified times of the day, behavior observations in the home, parental ratings of temperament, evaluation of reactivity and adaptation to developmentally appropriate challenges, and reactions to DPT inoculations. Included for these latter two procedures is monitoring of autonomic nervous system functioning (heart rate) and endocrine functioning (cortisol). The project has three specific goals: 1) To replicate and extend, with a longitudinal design, conclusions established in previous cross-cultural comparisons regarding community differences in the amount and patterning of sleep, daytime arousal, management of attention, and affective expression during the first two years of life. These differences appear to correspond to the way parents in the two communities interact with their babies and organize daily life for them; 2) To examine in greater detail the involvement of biologic mechanisms in the developmental pathways identified, particularly those involving autonomic functioning and activity of the hypothalamic-pituitary-adrenal axis; 3) To arrive at a clearer understanding of diversity in normative biobehavioral development as regulated through cultural processes. The product of this study will be new knowledge about how culturally organized environments interact over time with developing biological and behavioral systems to yield specific developmental outcomes. The results will inform current discussion about the causes of poor arousal regulation, attentional difficulty, sleep deprivation, and their consequences for social, cognitive, and self-regulatory functioning in the preschool years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALERTNESS

SOFTWARE

SYSTEM

FOR

PREDICTION

OF

SHIFTWORK

Principal Investigator & Institution: Heitmann, Anneke; Circadian Technologies, Inc. 24 Hartwell Ave Lexington, Ma 024213103 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-AUG-2004 Summary: (provided by applicant): A software system will be developed as a practical tool for accurately predicting alertness levels at work to help design bio-compatible work schedules and time the effective use of fatigue countermeasures. This software system can potentially benefit health and safety of a large portion of the working society. The core algorithm structure considers circadian and homeostatic aspects of sleep and alertness as well as time-on-task effects. The software system will use as input sleep and/or work patterns and individual characteristics (morningness/eveningness, habitual wake-up time) to generate a continuous alertness curve and statistical measures for work schedule evaluation. When the actual sleep pattern is not known, sleep will be predicted based on the work pattern. The algorithms of the modules for sleep and alertness prediction will be refined by optimization methods using error minimization techniques. The optimization process will use large training data sets on sleep and alertness patterns of shiftworkers with regular work schedules (to be collected during this project) and of workers with irregular work schedules (to be drawn from Circadian Technologies' extensive database). The predictive capability of the software system will be evaluated, using goodness-of-fit measures, by comparisons with Phase-I algorithms and by cross validations (using independent test data sets). PROPOSED COMMERCIAL APPLICATION: The progressive transition into a 24-hour society creates a large market for a software system for predicting alertness at work. This software system would be an attractive tool to design bio-compatible work schedules or to assess worker fatigue in accident investigations. The software system can also be used for worker training and public education regarding chronobiological and homeostatic aspects of sleep and sleepiness, and it can help increase awareness about the practical implications of fatigue at work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATE DEPENDENT ASPECTS OF COGNITION Principal Investigator & Institution: Stickgold, Robert A.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2004; Project Start 01-SEP-1993; Project End 30-NOV-2008 Summary: (provided by applicant): The last 10 years have witnessed an almost explosive growth in our knowledge of the roles that sleep may play in learning and memory consolidation, but several major issues remain. Much of the problem is due to the complexity of the systems involved; there are multiple forms of memories, multiple steps in memory consolidation, and multiple stages of sleep which might contribute to these processes. It thus becomes necessary to first ask what kinds of memory are affected by sleep, and then to ask what stages of sleep and what steps of memory consolidation are involved. Evidence exists for both declarative and procedural memory systems being sleep dependent, and in some cases, distinct components of the consolidation process may be sleep-dependent. But relatively few findings have been validated by multiple groups, and several are only being presented for the first time in the Preliminary Results section of this application. We propose to address these three fundamental unresolved issues. We will attempt to show (1) that sleep mediates consolidation of a new declarative memory task (Mandarin language study), (2) that

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slow wave sleep stabilizes and REM sleeps enhance perceptual learning, and (3) that sleep temporarily destabilizes motor skill learning as part of a process of sleep dependent consolidation. Confirming these hypotheses will significantly broaden our basic knowledge of the role of sleep in learning and memory consolidation. Western society has become a sleep deprived society, and this is especially true in the United States. There is a popular belief that the consequence of sleep deprivation is simply tiredness, that this can be overcome with effort or drugs, and that a good night's sleep on the weekend can completely reverse any deleterious effects of mid-week deprivation. Nowhere is this practice of "sleep bulimia," of weekly deprivation followed by weekend binge sleeping, more prevalent than on college campuses, although medical, public safety, and transportation personnel are also notoriously sleep deprived. All of these groups depend on continued education and learning for the effective performance of their tasks, and a clear understanding of exactly how sleep loss contributes to a failure of memory consolidation should provide important arguments to help counter this cultural drift towards less and less sleep. In addition, elucidation of the "sleep-memory connection" will enrich our understanding of the normal processes of learning and memory consolidation so critical to effectiveness in school and work, and help explain how sleep loss and sleep disorders lead to cognitive impairments in otherwise healthy individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRESS EFFECTS ON SLEEP: INFLUENCE OF GENES AND GENDER Principal Investigator & Institution: Turek, Fred W.; Professor; Neurobiology and Physiology; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: The overall objectives of the proposed experiments in this application are to develop the mouse as an animal model for elucidating the genetic and molecular mechanisms for sleep regulation and to tet specific hypotheses regarding the importance of the genetic background and physiological state of both male and female mice in the regulation of sleep as well as the effects of stress on sleep. Stress can have major disruptive effects on sleep as well as the circadian clock, which itself plays a fundamental role in the regulation of sleep. Both genetic and environmental factors contribute to the regulation of sleep as well as to how the sleep and circadian clock systems of any one individual will be affected by stress. In the proposed studies, the effects in mice of acute stress, chronic mild stress, and short- term sleep deprivation on sleep and circadian rhythms will be determined. Mice with genetic differences will be studied. These genetic differences will be polygenic for some studies, or will test the roles of single candidate genes in others. In view of gender differences in both sleep and the response to stress that have been observed in other species, primarily in humans, the proposed studies will include females in different stages of the estrous cycle and after the age-related loss in cyclicity. An additional objective of this proposal is to develop and validate the use of a novel automated sleep analysis system in the mouse. It is anticipated that these studies will contribute to an understanding of the mechanisms whereby stress impacts sleep regulation. The results of these studies also will form a critical basis for use of the tools of mouse genetics to identify genetic and physiological factors which may influence sleep disruption. Such information is likely ultimately to lead to more effective interventions for humans who suffer from sleep disturbances due to stress or related factors, and may lead to new treatments for mental and physical disorders associated with sleep-wage abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EFFECT OF SEDATION ON RESTORATIVE SLEEP Principal Investigator & Institution: Tung, Avery; Anesthesia and Critical Care; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 05-JUL-2001; Project End 30-JUN-2006 Summary: Sleep deprivation is common in the Intensive Care Unit (ICU) and can worsen outcomes. Recent introduction of propofol as an ICU sedative has allowed the widespread use of continuous sedation without delayed emergence. Such a strategy has been advocated to promote sleep. Although continuous sedation shares behavioral similarities with sleep, it is not known whether sedation effectively treats the sleepdeprived state. In principle, physiological and behavioral effects of sedation may either enhance or impair the ability of sleep to reverse the consequences of sleep deprivation. A period of sedation may itself alter the onset and intensity of sleep deprivation in the ICU. We seek to characterize the effects of continuous sedation on sleep with the longterm goal of understanding the neurobiological basis for the sleep-deprived state. The applicant has previously demonstrated in rats that prolonged sedation does not result in sleep deprivation, and that hypothalamic administration of propofol increases sleep. These findings suggest that a period of sedation is compatible with recovery from sleep deprivation, and imply that propofol may increase sleep by acting at a hypothalamic site. We hypothesize that the physiological consequences of sleep deprivation are reversed during prolonged use of continuous sedation. To test this hypothesis, we will 1) assess the ability of sedation to prevent sleep deprivation induced by environmental disruption, 2) compare the effects of continuous sedation with different agents on the restorative process associated with sleep, and 3) determine whether continuous sedation alters recovery sleep following sleep deprivation. We will acquire EEG/EMG and behavioral data in a rat model of sedation, sleep deprivation, and recovery. Using microdialysis, we will also measure extracellular adenosine concentrations in the basal forebrain before, during, and after sedation. Basal forebrain adenosine levels rise with prolonged wakefulness, and fall with recovery sleep. Little strategic importance has historically been assigned to preventing sleep deprivation in the ICU, partly because no proven method for treating sleep deprivation exists. Knowledge from this proposal will provide scientific insight into the relationships between anesthesia and sleep, and may lead to more effective clinical use of ICU sedatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF ADENOSINE IN WAKE/SLEEP TRANSITION Principal Investigator & Institution: Greene, Robert W.; Research Health Scientist; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2004; Project Start 16-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Adenosine (AD) activation of A1 adenosine receptors (A1R) can inhibit neurons of the brainstem and basal forebrain cholinergic arousal centers and facilitate slow wave sleep as demonstrated by the somnogenic effect of local application of exogenous AD to these centers. This suggests the hypothesis that local increases in AD, correlated with neuronal activity, are sufficient to facilitate slow wave sleep (SWS). This hypothesis may be tested by induction of temporally and anatomically restricted A1R gene deletion using transgenes with selective promotion of the recombinase, Cre, and with an adeno-associated viral vector that expresses the recombinase, Cre. The Cre recombinase will catalyze the gene deletion in transgenic mice with loxP sequences flanking the target, the functionally essential A1R exon. The deletion is predicted to increase waking under baseline conditions and to dampen the

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rebound sleep response to sleep deprivation. A physiologically relevant means of increasing A1R inhibition is by activation of NMDA receptors. This will be characterized in LDT using in vitro slice and whole cell voltage clamp recording techniques. AD cytoplasmic levels are in equilibrium with extracellular levels, and are, accordingly, of potential importance to extracellular, AD mediated inhibition and sleep/wake state modulation. The role of signal transduction processes in regulating the AD cytoplasmic levels will be investigated. The neuronal form of the major adenosine metabolizing enzyme, adenosine kinase (AK), will be characterized with regard to expression levels and localization at the RNA and protein level. The potential regulation of intracellular adenosine by protein phosphorylation/dephosphorylation of AK will be studied using a combination of molecular biological, protein biochemical, and neuropharmacological approaches. The state of phosphorylation of adenosine kinase across behavioral states and in response to sleep debt and rebound sleep will be assessed in whole animals (both rats and mice) and in brain slices. This may provide the requisite target cellular mechanism(s) for NMDA receptors and other potential modulators of extracellular AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CYTOKINES IN SLEEPINESS AND SLEEP APNEA Principal Investigator & Institution: Vgontzas, Alexandros N.; Professor; Psychiatry; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (applicant's abstract): Excessive daytime sleepiness (EDS) is a major public health concern, in part because individuals suffering from EDS often are not productive at work, are more susceptible to accidents, and generally are unable to function normally during the day. EDS is one of the major manifestations of individuals suffering from obstructive sleep apnea (OSA) and is frequently reported by obese individuals without sleep apnea. The mechanisms underlying EDS observed in both types of these individuals are not clear. We have recently demonstrated that the pro-inflammatory and fatigue-inducing cytokines, tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6), assayed in single plasma samples, are elevated in subjects with disorders of EDS. In addition, in preliminary studies, we demonstrated that these two cytokines are elevated in obese, compared to lean subjects, and that both sleep disturbance and obesity contribute to the cytokine elevation. More recently, we showed that daytime plasma levels of IL-6 are elevated in experimentally-induced EDS by the use of sleep deprivation and that a good night's sleep is associated with decreased daytime levels in healthy young subjects. There is a large literature implicating several pro-inflammatory cytokines in the regulation of sleep in animals; however, cytokine research on sleep in humans has been very limited. The fundamental hypothesis to be tested by the proposed studies is that the pro-inflammatory cytokines, TNFalpha and IL-6, are associated with and may contribute to EDS. We will test this hypothesis by determining the circadian secretory patterns of TNFalpha and IL-6 in plasma obtained from subjects that exhibit EDS associated with OSA or obesity. Also, we will determine whether nighttime nasal CPAP reduces daytime plasma TNFalpha and IL-6 concentrations in sleep apneics. In addition, we will experimentally induce EDS in healthy young subjects by the use of total sleep deprivation or one week of sleep restriction, which mimics real life-situations, to determine the relationship between the pattern of daytime plasma TNFalpha and IL-6 concentrations and daytime sleepiness as measured objectively using MSLT. Finally, we will assess the effects of daytime napping, in healthy subjects, on post-nap sleepiness and TNFalpha and IL-6 secretion. In these studies, we will use a series of experimental techniques including nighttime polysomnography, MSLT,

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computerized EEG, actigraphy, 24-hour blood sampling, 24-hour recording of core body temperature, and assays for TNFalpha and IL-6. These studies collectively will provide additional evidence for a role of TNFalpha and IL-6 in EDS and lay the foundation for the development of potential therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRAINING SCHEDULE EFFECTS ON SIMULATOR PERFORMANCE Principal Investigator & Institution: Cronin, John W.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2005 Summary: (provided by the applicant): Daily variations in physiologic and cognitive functions in human beings are driven by an endogenous circadian pacemaker. Human performance is further governed by the relative amounts of both chronic and acute sleep deprivation. Medical trainees, providing a significant amount of primary medical care in the U.S., are vulnerable to impaired performance and learning by virtue of schedules that demand long work hours. Surgical trainees, who are exposed to perhaps the greatest sleep deprivation and who are asked to perform critical tasks at adverse circadian phases, are a particularly important group. While much public policy debate has led to the mandate of reduced work hours, insufficient work has been done to determine the optimal work hours necessary to preserve top performance on critical tasks while preserving the educational opportunities for trainees. In June, 2003, ACGME work hour limitations loosely limit work hours to less than 80 hours a week and to no more than 24 hours of direct patient care. This proposal will attempt to work within that framework by testing surgical trainees on the following three schedules: 8-10 hour shift; 12-16 hour shift; and an on-call shift of 24-30 hours. Sleep will be characterized by actigraphy, diary self report, salivary cortisol assays and EEG recordings. Performance under these conditions will be measured using the MIST-VR laproscopic surgical simulator. Six critical tasks will be assessed for errors, efficiency and time on task and compared across the three schedules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VACHT EXPRESSION ACROSS SLEEP-WAKEFULNESS Principal Investigator & Institution: Greco, Mary Ann K.; Project Leader; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Over 70 million people in the U.S. are estimated to suffer from alterations in sleep-wakefulness. Existing therapies are of limited utility in treating these disorders. The difficulties in devising more effective treatments stem, in large part, from the fact that there is no one sleep center in the brain. As a result, the biological function(s) of sleep have not been elucidated. The neuronal circuitry underlying sleep-wakefulness is beginning to be understood. The intracellular events associated with the activity of these neurons across sleep-wakefulness, however, are not well defined. Understanding cellular mechanisms that occur during sleep is key to the identification of biological function(s). Acetylcholine (ACh) is associated with sleepwakefulness. Preliminary results examining the ACh synthesis enzyme, choline acetyltransferase (ChAT) are consistent with the hypothesis that sleep may play a role in maintaining neurotransmitter levels that are depleted during waking via changes in mRNA during sleep. The vesicular acetylcholine transporter (VAChT) performs the essential function of packaging nascent acetylcholine into vesicles. The gene encoding

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yacht lies within the gene encoding chat in all species examined, an extremely rare mammalian genomic organization. Preliminary studies suggest that chat and vacht mRNA levels are differentially expressed during sleep. In these studies, we focus first on delineating VAChT expression. In the first specific aim, we test the hypothesis that vacht mRNA and protein vary across individual sleep-wake bouts (i.e., waking, SWS and REM sleep) occurring over a 24h period. Preliminary studies of vacht mRNA suggest that it is higher during waking than during sleep. The second specific aim tests the hypothesis that mRNA and protein are associated with wakefulness. Initial results show vacht mRNA did not vary following six hours of sleep deprivation compared to controls. Specific aims 3 and 4 focus on comparisons of vacht and chat mRNAs, given the genomic organization of the genes and preliminary results that show that vacht mRNA contrasts with chat mRNA expression. Specific aim 3 tests the hypothesis that chat and vacht mRNAs are differentially expressed during sleep, while specific aim 4 tests the hypothesis that vacht mRNA subtypes are differentially expressed in response to sleep-wakefulness. Identification of these patterns of expression are key to understanding cellular mechanisms underlying sleep and wakefulness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WAKE/SLEEP DEVELOPMENT AND DEPRESSIVE SUBSTRATES Principal Investigator & Institution: Feng, Pingfu; Assistant Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2004; Project Start 16-DEC-2003; Project End 30-NOV-2006 Summary: (provided by applicant): Our long-term goal is to determine the role for neonatal rapid eye movement (REM) sleep in normal growth and development as well as in the determination of mood and sleep-wake behaviors in the adult. This is relevant to the neurobiologic and genetic mechanisms underlying depression. Extensive literature, including our previous studies, supports our hypothesis that neonatal REM sleep deprivation (RSD) alters the balance of development of wake promoting consequences and creates a disinhibited REM generation system that affects behavior and mood. Previous findings show that a rat with neonatal exposure to clomipramine has more REM sleep as an adult and our recent findings reveal that neonatal treatment with clomipramine reduce the brain levels of orexin B and/or delay the development of orexinergic neurons, which are identified as wake promotion neurons. This data supports a novel idea that neonatal RSD produces behavioral consequences by altering orexinergic as well as monoaminergic systems, then acting through MAPK signaltransduction pathways in the frontal cortex. We propose to test this hypothesis by examining the molecular changes occurring with wake/REM sleep alterations in two neonatal RSD models. One is made by treatment with REM sleep suppressant clomipramine and the other is made by non-pharmacological RSD. We will examine neuronal and molecular markers in the adult, the ontogenetic response of wake promoting related molecules to neonatal RSD, and interventions to reverse the effect of neonatal RSD. We will also examine the behavioral and molecular effect of the treatment by modulating wake regulation with either drug or non-drug methods and comparing with classic antidepressant. Results showing the impact of neonatal RSD on signaling pathways and on chronic changes in monoaminergic functions is relevant to a number of human illness, including depression and schizophrenia in the adult. Identifying modifiers of the adult behavioral alteration may provide insight into alternative countermeasures for these common illnesses. The present research plan addresses fundamental needs towards developing animal models of depression, the impact of sleep on the plasticity of systems regulating sleep and mood, and understanding the

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mechanisms of pharmacologic interventions. This proposal is also involved in a test of orexinergic effect on behavior and molecular alteration that may open a new scope toward the discovery of new antidepressant drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WORKING MEMORY IN OBSTRUCTIVE SLEEP APNEA-AN FMRI STUDY Principal Investigator & Institution: Thomas, Robert J.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Obstructive sleep apnea (OSA) is associated with abnormalities of higher order executive cognitive functions. The precise neuroanatomical localization of these deficits is unknown. The physiological correlates of executive cognitive dysfunction are poorly defined, and recovery following therapy may be incomplete. This project proposes the novel use of a neuroimaging technology, functional magnetic resonance imaging (fMRI), and precise neurobehavioral protocols, to localize the neuroanatomical site of dysfunction. Additional protocols will isolate specific physiological correlates of these neurocognitive abnormalities such as sleep fragmentation, sleep deprivation, and nocturnal oxygen desaturation and will relate them to altered regional cortical function. We will examine the cause of incomplete recovery of executive function while on therapy with nasal positive airway pressure. Working memory is a brain system that provides temporary storage and manipulation of information necessary to execute complex cognitive tasks, and it contributes to several executive functions. The n-back paradigm is an extensively used probe of working memory in MU studies, and is normally associated with activation of dorsolateral prefrontal cortex (DLPFC), anterior cingulate and posterior parietal cortex. We have adapted this task at the 2- back level of difficulty for use in OSA patients. Our preliminary data suggest a reversible (with treatment) reduction of working memory capacity in OSA patients that may be secondary to selective dysfunction in the DLPFC, relative to other nodes in the executive control network. Based on this data we hypothesize that: 1) Patients with OSA have reduced activation of the DLPFC, relative to posterior parietal cortex during tests of working memory. 2) Sleep deprivation or fragmentation but not nocturnal hypoxia disrupts working memory in normal subjects. 3). Post-treatment residual abnormalities are caused by persisting sleep fragmentation, not prior hypoxic exposure. The P.I. has training in general medicine, neurology, sleep disorders and functional neuroimaging. The proposed projects will be performed under the direct guidance of experts in sleep disorders, cognitive neuroscience, and fMRI within the Harvard system. The relevant research environment is particularly rich at the participating institutions-basic and applied neurobiology of sleep, clinical sleep disorders, behavioral neurology, and fMRI. The career development plan will include training in MRI physics, applied MRI, statistics and research methodology, ethics, planning of clinical research, and cognitive neuroscience. The immediate career goal is to acquire the necessary skills for applied clinical fMRI and determine the functional neurocircuitry of the localization, etiology and recovery of reduced working memory capacity in patients with OSA using the 2-back task paradigm. The longterm career goal is to develop a model of the function of sleep by demonstrating the functional consequences of sleep disruption in conditions such as depression, age-related memory dysfunction, and attention deficit hyperactivity disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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.3 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 sleep deprivation, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “sleep deprivation” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for sleep deprivation (hyperlinks lead to article summaries): •

A clinical trial of sleep deprivation in combination with antidepressant medication. Author(s): Leibenluft E, Moul DE, Schwartz PJ, Madden PA, Wehr TA. Source: Psychiatry Research. 1993 March; 46(3): 213-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8493292&dopt=Abstract

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A comparative study of the diagnosis value of drug-induced sleep EEGs and sleep EEGs following sleep deprivation in patients with complex partial seizures. Author(s): Degen R, Degen HE. Source: Journal of Neurology. 1981; 225(2): 85-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6164768&dopt=Abstract

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A comparison of tyrosine against placebo, phentermine, caffeine, and Damphetamine during sleep deprivation. Author(s): Waters WF, Magill RA, Bray GA, Volaufova J, Smith SR, Lieberman HR, Rood J, Hurry M, Anderson T, Ryan DH. Source: Nutritional Neuroscience. 2003 August; 6(4): 221-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887139&dopt=Abstract

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A review of studies concerning effects of sleep deprivation and fatigue on residents' performance. Author(s): Samkoff JS, Jacques CH. Source: Academic Medicine : Journal of the Association of American Medical Colleges. 1991 November; 66(11): 687-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1747181&dopt=Abstract

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A turning point for mood during sleep deprivation therapy--does it exist? Author(s): Haug HJ, Fahndrich E. Source: Pharmacopsychiatry. 1988 November; 21(6): 418-9. Erratum In: Pharmacopsychiatry 1989 March; 22(2): 92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3244781&dopt=Abstract

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Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortriptyline, or placebo. Author(s): Green TD, Reynolds CF 3rd, Mulsant BH, Pollock BG, Miller MD, Houck PR, Mazumdar S, Dew MA, Kupfer DJ. Source: Journal of Geriatric Psychiatry and Neurology. 1999 Summer; 12(2): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483927&dopt=Abstract

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Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine. Author(s): Bump GM, Reynolds CF 3rd, Smith G, Pollock BG, Dew MA, Mazumdar S, Geary M, Houck PR, Kupfer DJ. Source: Depression and Anxiety. 1997; 6(3): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9442985&dopt=Abstract

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Adenosine and antidepressant effects of sleep deprivation. Author(s): Lara DR, Souza DO. Source: The American Journal of Psychiatry. 2000 October; 157(10): 1707-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007739&dopt=Abstract

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Advanced vs. normal sleep timing: effects on depressed mood after response to sleep deprivation in patients with a major depressive disorder. Author(s): Riemann D, Hohagen F, Konig A, Schwarz B, Gomille J, Voderholzer U, Berger M. Source: Journal of Affective Disorders. 1996 April 12; 37(2-3): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8731074&dopt=Abstract

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Aerobic and anaerobic contributions to exhaustive high-intensity exercise after sleep deprivation. Author(s): Hill DW, Borden DO, Darnaby KM, Hendricks DN. Source: Journal of Sports Sciences. 1994 October; 12(5): 455-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7799474&dopt=Abstract

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Aerobic fitness and hormonal responses to prolonged sleep deprivation and sustained mental work. Author(s): Radomski MW, Hart LE, Goodman JM, Plyley MJ. Source: Aviation, Space, and Environmental Medicine. 1992 February; 63(2): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1347679&dopt=Abstract

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Age-dependent suppression of nocturnal growth hormone levels during sleep deprivation. Author(s): Mullington J, Hermann D, Holsboer F, Pollmacher T. Source: Neuroendocrinology. 1996 September; 64(3): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8875441&dopt=Abstract

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Aging does not affect the sleep endocrine response to total sleep deprivation in humans. Author(s): Murck H, Antonijevic IA, Schier T, Frieboes RM, Barthelmes J, Steiger A. Source: Neurobiology of Aging. 1999 November-December; 20(6): 665-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674432&dopt=Abstract

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Alertness and memory after sleep deprivation and diazepam intake. Author(s): Gorissen M, Tielemans M, Coenen A. Source: Journal of Psychopharmacology (Oxford, England). 1997; 11(3): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9305415&dopt=Abstract

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Alpha activity in the human REM sleep EEG: topography and effect of REM sleep deprivation. Author(s): Roth C, Achermann P, Borbely AA. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 April; 110(4): 632-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10378731&dopt=Abstract

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Alterations in the morning plasma levels of hormones and the endocrine responses to bicycle exercise during prolonged strain. The significance of energy and sleep deprivation. Author(s): Opstad PK. Source: Acta Endocrinol (Copenh). 1991 July; 125(1): 14-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1872119&dopt=Abstract

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Alterations of blood platelet MAO-B activity and LSD-binding in humans after sleep deprivation and recovery sleep. Author(s): Schreiber W, Opper C, Dickhaus B, Heiser P, Wesemann W, Krieg JC. Source: Journal of Psychiatric Research. 1997 May-June; 31(3): 323-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9306290&dopt=Abstract

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Alterations of host defence system after sleep deprivation are followed by impaired mood and psychosocial functioning. Author(s): Heiser P, Dickhaus B, Opper C, Hemmeter U, Remschmidt H, Wesemann W, Krieg JC, Schreiber W. Source: World J Biol Psychiatry. 2001 April; 2(2): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587190&dopt=Abstract

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Altered brain response to verbal learning following sleep deprivation. Author(s): Drummond SP, Brown GG, Gillin JC, Stricker JL, Wong EC, Buxton RB. Source: Nature. 2000 February 10; 403(6770): 655-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10688201&dopt=Abstract

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Amitriptyline in combination with repeated late sleep deprivation versus amitriptyline alone in major depression. A randomised study. Author(s): Kuhs H, Farber D, Borgstadt S, Mrosek S, Tolle R. Source: Journal of Affective Disorders. 1996 February 12; 37(1): 31-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8682976&dopt=Abstract

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Amplitude reduction in visual event-related potentials as a function of sleep deprivation. Author(s): Corsi-Cabrera M, Arce C, Del Rio-Portilla IY, Perez-Garci E, Guevara MA. Source: Sleep. 1999 March 15; 22(2): 181-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10201062&dopt=Abstract

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Antidepressant effects of light therapy combined with sleep deprivation are influenced by a functional polymorphism within the promoter of the serotonin transporter gene. Author(s): Benedetti F, Colombo C, Serretti A, Lorenzi C, Pontiggia A, Barbini B, Smeraldi E. Source: Biological Psychiatry. 2003 October 1; 54(7): 687-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512208&dopt=Abstract

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Antidepressant response to sleep deprivation as a function of time into depressive episode in rapidly cycling bipolar patients. Author(s): Gill DS, Ketter TA, Post RM. Source: Acta Psychiatrica Scandinavica. 1993 February; 87(2): 102-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8447235&dopt=Abstract

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Antidepressant responses and changes in visual adaptation after sleep deprivation. Author(s): Sokolski KN, Reist C, Chen CC, DeMet EM. Source: Psychiatry Research. 1995 August 28; 57(3): 197-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7501729&dopt=Abstract

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Antidepressive response to sleep deprivation in unipolar depression is not associated with dopamine D3 receptor genotype. Author(s): Schumann G, Benedetti F, Voderholzer U, Kammerer N, Hemmeter U, Travers HW, Fiebich B, Holsboer-Trachsler E, Berger M, Seifritz E, Ebert D. Source: Neuropsychobiology. 2001; 43(3): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11287789&dopt=Abstract

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Are postoperative complications related to resident sleep deprivation? Author(s): Haynes DF, Schwedler M, Dyslin DC, Rice JC, Kerstein MD. Source: Southern Medical Journal. 1995 March; 88(3): 283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7886523&dopt=Abstract

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Are there predictors for sleep deprivation response in depressed patients? Author(s): Riemann D, Wiegand M, Berger M. Source: Biological Psychiatry. 1991 April 1; 29(7): 707-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2054442&dopt=Abstract

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Assessing vigilance through a brief pencil and paper letter cancellation task (LCT): effects of one night of sleep deprivation and of the time of day. Author(s): Casagrande M, Violani C, Curcio G, Bertini M. Source: Ergonomics. 1997 June; 40(6): 613-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9174413&dopt=Abstract

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Atrial natriuretic peptide in plasma after prolonged physical strain, energy deficiency and sleep deprivation. Author(s): Opstad PK, Haugen AH, Sejersted OM, Bahr R, Skrede KK. Source: European Journal of Applied Physiology and Occupational Physiology. 1994; 68(2): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8194540&dopt=Abstract

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Auditory arousal thresholds after selective slow-wave sleep deprivation. Author(s): Ferrara M, De Gennaro L, Casagrande M, Bertini M. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 December; 110(12): 2148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616120&dopt=Abstract

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Behavioral and subjective effects of marijuana following partial sleep deprivation. Author(s): Liguori A, Gatto CP, Jarrett DB, McCall WV, Brown TW. Source: Drug and Alcohol Dependence. 2003 June 5; 70(3): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757961&dopt=Abstract

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Binocular convergence in man during total sleep deprivation. Author(s): Horne JA. Source: Biological Psychology. 1975 December; 3(4): 309-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1212488&dopt=Abstract

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Biological and behavioral effects of one night's sleep deprivation in depressed patients and normals. Author(s): Gerner RH, Post RM, Gillin JC, Bunney WE Jr. Source: Journal of Psychiatric Research. 1979; 15(1): 21-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=219193&dopt=Abstract

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Biperiden administration during REM sleep deprivation diminished the frequency of REM sleep attempts. Author(s): Salin-Pascual RJ, Grandos-Fuentes D, Galicia-Polo L, Nieves E, Roehrs TA, Roth T. Source: Sleep. 1992 June; 15(3): 252-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1621026&dopt=Abstract

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Biperiden administration in normal sleep and after rapid eye movement sleep deprivation in healthy volunteers. Author(s): Salin-Pascual RJ, Granados-Fuentes D, Galicia-Polo L, Nieves E, Echeverry J. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1991 September; 5(2): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1930618&dopt=Abstract

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Blunted prolactin response to fentanyl in depression. Normalizing effect of partial sleep deprivation. Author(s): Frecska E, Perenyi A, Arato M. Source: Psychiatry Research. 2003 May 30; 118(2): 155-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798980&dopt=Abstract

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Body core temperature and depression during total sleep deprivation in depressives. Author(s): Elsenga S, Van den Hoofdakker RH. Source: Biological Psychiatry. 1988 September; 24(5): 531-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3167142&dopt=Abstract

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Bright light therapy stabilizes the antidepressant effect of partial sleep deprivation. Author(s): Neumeister A, Goessler R, Lucht M, Kapitany T, Bamas C, Kasper S. Source: Biological Psychiatry. 1996 January 1; 39(1): 16-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8719121&dopt=Abstract

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Caffeine effects on marksmanship during high-stress military training with 72 hour sleep deprivation. Author(s): Tharion WJ, Shukitt-Hale B, Lieberman HR. Source: Aviation, Space, and Environmental Medicine. 2003 April; 74(4): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688447&dopt=Abstract

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Caffeine reversal of sleep deprivation effects on alertness and mood. Author(s): Penetar D, McCann U, Thorne D, Kamimori G, Galinski C, Sing H, Thomas M, Belenky G. Source: Psychopharmacology. 1993; 112(2-3): 359-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871042&dopt=Abstract

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Can critically timed sleep deprivation be useful in pregnancy and postpartum depressions? Author(s): Parry BL, Curran ML, Stuenkel CA, Yokimozo M, Tam L, Powell KA, Gillin JC. Source: Journal of Affective Disorders. 2000 November; 60(3): 201-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074109&dopt=Abstract

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Can negative self-schemes in depressives be altered through sleep deprivation? Author(s): Baving L, Maes H, Bohus M, Lis S, Krieger S, Olbrich H, Berger M. Source: Journal of Affective Disorders. 1997 February; 42(2-3): 93-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9105950&dopt=Abstract

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Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow? Author(s): Volk SA, Kaendler SH, Hertel A, Maul FD, Manoocheri R, Weber R, Georgi K, Pflug B, Hor G. Source: Psychiatry Research. 1997 September 29; 75(2): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9351489&dopt=Abstract

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Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Pollock B, Derbyshire S, Nofzinger E, Dew MA, Houck PR, Milko D, Meltzer CC, Kupfer DJ. Source: The American Journal of Psychiatry. 1999 May; 156(5): 683-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327899&dopt=Abstract

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Changes in 24-hour urinary excretion of MHPG after four continuous nights of REM sleep deprivation in human volunteers. Author(s): Salin-Pascual RJ, Angulo LN, de la Fuente JR. Source: Psychiatry Research. 1989 November; 30(2): 155-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2616685&dopt=Abstract

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Changes in direct current potentials during sleep deprivation. Author(s): Hoffmann RF, Bonato RA, Armitage R, Wimmer FL. Source: Journal of Sleep Research. 1996 September; 5(3): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8956203&dopt=Abstract

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Changes in the circadian rhythm of serum iron induced by a 5-day sleep deprivation. Author(s): Kuhn E, Brodan V. Source: European Journal of Applied Physiology and Occupational Physiology. 1982; 49(2): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6889498&dopt=Abstract

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Changes in the waking EEG as a consequence of sleep and sleep deprivation. Author(s): Corsi-Cabrera M, Ramos J, Arce C, Guevara MA, Ponce-de Leon M, Lorenzo I. Source: Sleep. 1992 December; 15(6): 550-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1475570&dopt=Abstract

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Chewing can relieve sleepiness in a night of sleep deprivation. Author(s): Hodoba D. Source: Sleep Res Online. 1999; 2(4): 101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382890&dopt=Abstract

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Chloral hydrate and sleep deprivation for sedation during flexible fiberoptic bronchoscopy. Author(s): Callahan CW. Source: Pediatric Pulmonology. 1997 October; 24(4): 302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9368267&dopt=Abstract

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Chlorpromazine versus sleep deprivation in activation of EEG in adult-onset partial epilepsy. Author(s): Aguglia U, Gambardella A, Le Piane E, De Sarro GB, Zappia M, Quattrone A. Source: Journal of Neurology. 1994 October; 241(10): 605-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7836964&dopt=Abstract

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Circadian rhythm of rectal temperature during sleep deprivation with modafinil. Author(s): Launay JC, Savourey G, Guinet A, Lallement G, Besnard Y, Bittel J. Source: Aviation, Space, and Environmental Medicine. 2002 October; 73(10): 985-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398260&dopt=Abstract

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Circadian rhythms (temperature, heart rate, vigilance, mood) of short and long sleepers: effects of sleep deprivation. Author(s): Benoit O, Foret J, Merle B, Reinberg A. Source: Chronobiologia. 1981 October-December; 8(4): 341-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7327054&dopt=Abstract

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Circadian rhythms of prolactin and thyroid-stimulating hormone during the menstrual cycle and early versus late sleep deprivation in premenstrual dysphoric disorder. Author(s): Parry BL, Hauger R, LeVeau B, Mostofi N, Cover H, Clopton P, Gillin JC. Source: Psychiatry Research. 1996 May 17; 62(2): 147-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8771612&dopt=Abstract

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Circadian variations in cardiovascular parameters during sleep deprivation. A noninvasive study of young healthy men. Author(s): Ahnve S, Theorell T, Akerstedt T, Froberg JE, Halberg F. Source: European Journal of Applied Physiology and Occupational Physiology. 1981; 46(1): 9-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7194788&dopt=Abstract

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Clinical caveat: prior sleep deprivation can affect the MSLT for days. Author(s): Janjua T, Samp T, Cramer-Bornemann M, Hannon H, Mahowald MW. Source: Sleep Medicine. 2003 January; 4(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592363&dopt=Abstract

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Clinical effects of sleep fragmentation versus sleep deprivation. Author(s): Bonnet MH, Arand DL. Source: Sleep Medicine Reviews. 2003 August; 7(4): 297-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505597&dopt=Abstract

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Clinical response to sleep deprivation and auditory-evoked potentials--preliminary results. Author(s): Danos P, Kasper S, Scholl HP, Kaiser J, Ruhrmann S, Hoflich G, Moller HJ. Source: Pharmacopsychiatry. 1994 March; 27(2): 70-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8029315&dopt=Abstract

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Cognitive deterioration and changes of P300 during total sleep deprivation. Author(s): Lee HJ, Kim L, Suh KY. Source: Psychiatry and Clinical Neurosciences. 2003 October; 57(5): 490-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950703&dopt=Abstract

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Cold thermoregulatory changes induced by sleep deprivation in men. Author(s): Savourey G, Bittel J. Source: European Journal of Applied Physiology and Occupational Physiology. 1994; 69(3): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8001532&dopt=Abstract

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Combination of bright light and caffeine as a countermeasure for impaired alertness and performance during extended sleep deprivation. Author(s): Wright KP Jr, Badia P, Myers BL, Plenzler SC. Source: Journal of Sleep Research. 1997 March; 6(1): 26-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9125696&dopt=Abstract

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Combined effects of shift work and life-style on the prevalence of insomnia, sleep deprivation and daytime sleepiness. Author(s): Harma M, Tenkanen L, Sjoblom T, Alikoski T, Heinsalmi P. Source: Scand J Work Environ Health. 1998 August; 24(4): 300-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754862&dopt=Abstract

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Comparing the effects of sleep loss after experimental sleep deprivation and in clinical patients. Author(s): Cluydts R. Source: Sleep Medicine Reviews. 2003 August; 7(4): 293-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505596&dopt=Abstract

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Comparison of the effects of sleep deprivation, alcohol and obstructive sleep apnoea (OSA) on simulated steering performance. Author(s): Hack MA, Choi SJ, Vijayapalan P, Davies RJ, Stradling JR. Source: Respiratory Medicine. 2001 July; 95(7): 594-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453317&dopt=Abstract

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Complexity and non-linear description of diurnal cortisol and growth hormone secretory patterns before and after sleep deprivation. Author(s): Ilias I, Vgontzas AN, Provata A, Mastorakos G. Source: Endocrine Regulations. 2002 June; 36(2): 63-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207555&dopt=Abstract

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Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study. Author(s): Civardi C, Boccagni C, Vicentini R, Bolamperti L, Tarletti R, Varrasi C, Monaco F, Cantello R. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 December; 71(6): 80912. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723210&dopt=Abstract

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Cortisol and beta-endorphin responses to sleep deprivation in major depression--the hyperarousal theories of sleep deprivation. Author(s): Ebert D, Kaschka WP, Loew T, Beck G. Source: Neuropsychobiology. 1994; 29(2): 64-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8170528&dopt=Abstract

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Cortisol circadian rhythms during the menstrual cycle and with sleep deprivation in premenstrual dysphoric disorder and normal control subjects. Author(s): Parry BL, Javeed S, Laughlin GA, Hauger R, Clopton P. Source: Biological Psychiatry. 2000 November 1; 48(9): 920-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074230&dopt=Abstract

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Decoupling motor memory strategies: effects of sleep deprivation and amphetamine. Author(s): Cochran JC, Thorne DR, Penetar DM, Newhouse PA. Source: The International Journal of Neuroscience. 1994 January-February; 74(1-4): 4554. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7928114&dopt=Abstract

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Decrease in motor cortical excitability in human subjects after sleep deprivation. Author(s): Manganotti P, Palermo A, Patuzzo S, Zanette G, Fiaschi A. Source: Neuroscience Letters. 2001 May 25; 304(3): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343825&dopt=Abstract

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Decreased attentional responsivity during sleep deprivation: orienting response latency, amplitude, and habituation. Author(s): McCarthy ME, Waters WF. Source: Sleep. 1997 February; 20(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9143071&dopt=Abstract

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Decreased serum levels of oestradiol, testosterone and prolactin during prolonged physical strain and sleep deprivation, and the influence of a high calorie diet. Author(s): Opstad PK, Aakvaag A. Source: European Journal of Applied Physiology and Occupational Physiology. 1982; 49(3): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6890449&dopt=Abstract

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Deficient nocturnal surge of TSH secretion during sleep and sleep deprivation in rapid-cycling bipolar illness. Author(s): Sack DA, James SP, Rosenthal NE, Wehr TA. Source: Psychiatry Research. 1988 February; 23(2): 179-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3129751&dopt=Abstract

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Delta sleep ratio as a predictor of sleep deprivation response in major depression. Author(s): Nissen C, Feige B, Konig A, Voderholzer U, Berger M, Riemann D. Source: Journal of Psychiatric Research. 2001 May-June; 35(3): 155-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11461711&dopt=Abstract

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Detection of juvenile sleep deprivation by stochastic optimization of pupillographic records. Author(s): O'Neill W, Mercer P, Sheldon S, Kotsos T. Source: Methods of Information in Medicine. 2003; 42(3): 282-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874663&dopt=Abstract

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Dexamethasone suppression test and sleep deprivation in endogenous depression. Author(s): Kuhs H. Source: Journal of Affective Disorders. 1985 September; 9(2): 121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2932484&dopt=Abstract

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Dexamethasone suppression test combined with total sleep deprivation in depressed patients. Author(s): Kasper S, Moises HW, Beckmann H. Source: Psychiatr Clin (Basel). 1983; 16(1): 17-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6844658&dopt=Abstract

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Diagnostic applications of sleep deprivation. Author(s): Letemendia FJ, Prowse AW, Southmayd SE. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1986 November; 31(8): 731-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3791126&dopt=Abstract

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Dichotic listening and sleep deprivation: vigilance effects. Author(s): Johnsen BH, Laberg JC, Eid J, Hugdahl K. Source: Scandinavian Journal of Psychology. 2002 December; 43(5): 413-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500780&dopt=Abstract

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Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: clinical and theoretical implications. Author(s): Post RM, Uhde TW, Rubinow DR, Huggins T. Source: Psychiatry Research. 1987 September; 22(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3659217&dopt=Abstract

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Direct comparison of total sleep deprivation and late partial sleep deprivation in the treatment of major depression. Author(s): Giedke H, Klingberg S, Schwarzler F, Schweinsberg M. Source: Journal of Affective Disorders. 2003 September; 76(1-3): 85-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943937&dopt=Abstract

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Displacement of the sleep period and sleep deprivation. Implications for shift work. Author(s): Akerstedt T, Gillberg M. Source: Hum Neurobiol. 1982; 1(3): 163-71. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6764463&dopt=Abstract

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Diurnal change in stature: effects of sleep deprivation in young men and middle-aged men. Author(s): Jazwinska EC, Adam K. Source: Experientia. 1985 December 15; 41(12): 1533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4076396&dopt=Abstract

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Diurnal rhythm of axillary temperature in long and short sleepers: effects of sleep deprivation and sleep displacement. Author(s): Benoit O, Foret J, Merle B, Bouard G. Source: Sleep. 1981; 4(4): 359-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7198285&dopt=Abstract

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Does the sedation resulting from sleep deprivation and lorazepam cause similar cognitive deficits? Author(s): Fluck E, File SE, Springett J, Kopelman MD, Rees J, Orgill J. Source: Pharmacology, Biochemistry, and Behavior. 1998 April; 59(4): 909-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9586848&dopt=Abstract

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Dopamine agonist amineptine prevents the antidepressant effect of sleep deprivation. Author(s): Benedetti F, Barbini B, Campori E, Colombo C, Smeraldi E. Source: Psychiatry Research. 1996 December 20; 65(3): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9029666&dopt=Abstract

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Dopamine receptor D2 and D3 gene variants are not associated with the antidepressant effect of total sleep deprivation in bipolar depression. Author(s): Benedetti F, Serretti A, Colombo C, Lilli R, Lorenzi C, Smeraldi E. Source: Psychiatry Research. 2003 June 15; 118(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834818&dopt=Abstract

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Dopamine receptor D4 is not associated with antidepressant activity of sleep deprivation. Author(s): Serretti A, Benedetti F, Colombo C, Lilli R, Lorenzi C, Smeraldi E. Source: Psychiatry Research. 1999 December 20; 89(2): 107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646829&dopt=Abstract

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Dopaminergic augmentation of sleep deprivation effects in bipolar depression. Author(s): Benedetti F, Campori E, Barbini B, Fulgosi MC, Colombo C. Source: Psychiatry Research. 2001 November 30; 104(3): 239-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728613&dopt=Abstract

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Dose-dependent caffeine pharmacokinetics during severe sleep deprivation in humans. Author(s): Kamimori GH, Lugo SI, Penetar DM, Chamberlain AC, Brunhart GE, Brunhart AE, Eddington ND. Source: Int J Clin Pharmacol Ther. 1995 March; 33(3): 182-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7599918&dopt=Abstract

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DST in healthy volunteers and after sleep deprivation. Author(s): Klein HE, Seibold B. Source: Acta Psychiatrica Scandinavica. 1985 July; 72(1): 16-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4036655&dopt=Abstract

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Dynamics of electroencephalographic sleep spindles and slow wave activity in men: effect of sleep deprivation. Author(s): Dijk DJ, Hayes B, Czeisler CA. Source: Brain Research. 1993 October 29; 626(1-2): 190-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8281430&dopt=Abstract

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Effect of bright light on EEG activities and subjective sleepiness to mental task during nocturnal sleep deprivation. Author(s): Yokoi M, Aoki K, Shiomura Y, Iwanaga K, Katsuura T. Source: Journal of Physiological Anthropology and Applied Human Science. 2003 November; 22(6): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14646259&dopt=Abstract

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Effect of sleep deprivation and driving duration on the useful visual field in younger and older subjects during simulator driving. Author(s): Roge J, Pebayle T, El Hannachi S, Muzet A. Source: Vision Research. 2003 June; 43(13): 1465-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767314&dopt=Abstract

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Effect of sleep deprivation on driving safety in housestaff. Author(s): Marcus CL, Loughlin GM. Source: Sleep. 1996 December; 19(10): 763-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085483&dopt=Abstract

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Effect of sleep deprivation on medical resident and student cognitive function: A prospective study. Author(s): Halbach MM, Spann CO, Egan G. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748477&dopt=Abstract

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Effect of sleep deprivation on saccades and eyelid blinking. Author(s): Crevits L, Simons B, Wildenbeest J. Source: European Neurology. 2003; 50(3): 176-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530625&dopt=Abstract

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Effect of sleep deprivation on the growth hormone response to the alpha-3 adrenergic receptor agonist, clonidine, in normal subjects. Author(s): Lal S, Thavundayil JX, Krishnan B, Nair NP, Schwartz G, Kiely ME, Guyda H. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1997; 104(2-3): 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9203090&dopt=Abstract

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Effect of sleep deprivation on the performance of simulated laparoscopic surgical skill. Author(s): Eastridge BJ, Hamilton EC, O'Keefe GE, Rege RV, Valentine RJ, Jones DJ, Tesfay S, Thal ER. Source: American Journal of Surgery. 2003 August; 186(2): 169-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885613&dopt=Abstract

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Effect of total sleep deprivation on the landmarks of stage 2 sleep. Author(s): Curcio G, Ferrara M, Pellicciari MC, Cristiani R, De Gennaro L. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 December; 114(12): 2279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652087&dopt=Abstract

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Effects of sleep deprivation and sleep fragmentation on upper airway collapsibility in normal subjects. Author(s): Series F, Roy N, Marc I. Source: American Journal of Respiratory and Critical Care Medicine. 1994 August; 150(2): 481-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8049833&dopt=Abstract

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Effects of sleep deprivation on naval seamen: II. Short recovery sleep on performance. Author(s): Foo SC, How J, Siew MG, Wong TM, Vijayan A, Kanapathy R. Source: Ann Acad Med Singapore. 1994 September; 23(5): 676-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7847746&dopt=Abstract

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Effects of sleep deprivation on performance of Naval seamen: I. Total sleep deprivation on performance. Author(s): How JM, Foo SC, Low E, Wong TM, Vijayan A, Siew MG, Kanapathy R. Source: Ann Acad Med Singapore. 1994 September; 23(5): 669-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7847745&dopt=Abstract

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Effects of sleep deprivation on performance: a meta-analysis. Author(s): Pilcher JJ, Huffcutt AI. Source: Sleep. 1996 May; 19(4): 318-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8776790&dopt=Abstract

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Effects of sleep deprivation on serotonin function in depression. Author(s): Salomon RM, Delgado PL, Licinio J, Krystal JH, Heninger GR, Charney DS. Source: Biological Psychiatry. 1994 December 15; 36(12): 840-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7893848&dopt=Abstract

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Effects of sleep deprivation with reference to military operations. Author(s): Giam GC. Source: Ann Acad Med Singapore. 1997 January; 26(1): 88-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9140584&dopt=Abstract

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Effects of sleep on the antidepressant response to sleep deprivation. Author(s): Reist C, Chen CC, Chhoeu A, Berry RB, Bunney WE Jr. Source: Biological Psychiatry. 1994 May 15; 35(10): 794-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8043709&dopt=Abstract

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Effects of slow-release caffeine and a nap on driving simulator performance after partial sleep deprivation. Author(s): De Valck E, De Groot E, Cluydts R. Source: Percept Mot Skills. 2003 February; 96(1): 67-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705512&dopt=Abstract

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Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation. Author(s): Magill RA, Waters WF, Bray GA, Volaufova J, Smith SR, Lieberman HR, McNevin N, Ryan DH. Source: Nutritional Neuroscience. 2003 August; 6(4): 237-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887140&dopt=Abstract

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Elevated salivary cortisol due to sleep deprivation. Author(s): Alexander A. Source: Occupational Medicine (Oxford, England). 2003 September; 53(6): 409; Author Reply 410. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514912&dopt=Abstract

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Erythrocyte magnesium and prostaglandin dynamics in chronic sleep deprivation. Author(s): Tanabe K, Osada N, Suzuki N, Nakayama M, Yokoyama Y, Yamamoto A, Oya M, Murabayashi T, Yamamoto M, Omiya K, Itoh H, Murayama M. Source: Clin Cardiol. 1997 March; 20(3): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9068914&dopt=Abstract

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Eye-blink rates and depression. Is the antidepressant effect of sleep deprivation mediated by the dopamine system? Author(s): Ebert D, Albert R, Hammon G, Strasser B, May A, Merz A. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1996 October; 15(4): 332-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8887987&dopt=Abstract

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Failure of sleep deprivation to prolong seizures in ECT. Author(s): Kellner CH, Malcolm RL. Source: The American Journal of Psychiatry. 1988 April; 145(4): 530. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3348459&dopt=Abstract

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Female exposure to high G: performance of simulated flight after 24 hours of sleep deprivation. Author(s): Chelette TL, Albery WB, Esken RL, Tripp LD. Source: Aviation, Space, and Environmental Medicine. 1998 September; 69(9): 862-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9737757&dopt=Abstract

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Five variations of sleep deprivation in a depressed woman. Author(s): Knowles JB, Southmayd SE, Delva N, MacLean AW, Cairns J, Letemendia FJ. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1979 November; 135: 403-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=540205&dopt=Abstract

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Functional analysis and treatment of escape-maintained aggression correlated with sleep deprivation. Author(s): O'Reilly MF. Source: J Appl Behav Anal. 1995 Summer; 28(2): 225-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7601805&dopt=Abstract

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Galanin has REM-sleep deprivation-like effects on the sleep EEG in healthy young men. Author(s): Murck H, Antonijevic IA, Frieboes RM, Maier P, Schier T, Steiger A. Source: Journal of Psychiatric Research. 1999 May-June; 33(3): 225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367988&dopt=Abstract

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General considerations of sleep and sleep deprivation. Author(s): Jovanovic UJ. Source: Epilepsy Res Suppl. 1991; 2: 205-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1760089&dopt=Abstract

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Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Houck PR, Dew MA, Ma Y, Mulsant BH, Pollock BG. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2002 September-October; 10(5): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213690&dopt=Abstract

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Glycogenic response of CNS to paradoxical sleep deprivation in cats and rats. Author(s): Karadzic V, Mrsulja B. Source: Electroencephalography and Clinical Neurophysiology. 1969 November; 27(5): 552. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4187071&dopt=Abstract

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Granulocyte chemiluminescence response to serum opsonized zymosan particles ex vivo during long-term strenuous exercise, energy and sleep deprivation in humans. Author(s): Wiik P, Opstad PK, Boyum A. Source: European Journal of Applied Physiology and Occupational Physiology. 1996; 73(3-4): 251-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8781854&dopt=Abstract

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Green light attenuates melatonin output and sleepiness during sleep deprivation. Author(s): Horne JA, Donlon J, Arendt J. Source: Sleep. 1991 June; 14(3): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1896724&dopt=Abstract

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Habitual sleep length and patterns of recovery sleep after 24 hour and 36 hour sleep deprivation. Author(s): Benoit O, Foret J, Bouard G, Merle B, Landau J, Marc ME. Source: Electroencephalography and Clinical Neurophysiology. 1980 December; 50(5-6): 477-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6160990&dopt=Abstract

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Health effects of sleep deprivation. Author(s): Naitoh P, Kelly TL, Englund C. Source: Occupational Medicine (Philadelphia, Pa.). 1990 April-June; 5(2): 209-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2203156&dopt=Abstract

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Hemisphere-specific deficits on cognitive/perceptual tasks following REM sleep deprivation. Author(s): Dushenko TW, Sterman MB. Source: The International Journal of Neuroscience. 1984 December; 25(1-2): 25-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6526590&dopt=Abstract

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High incentive effects on vigilance performance during 72 hours of total sleep deprivation. Author(s): Horne JA, Pettitt AN. Source: Acta Psychologica. 1985 February; 58(2): 123-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3984776&dopt=Abstract

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Homeostatic process and sleep spindles in patients with sleep-maintenance insomnia: effect of partial (21 h) sleep deprivation. Author(s): Besset A, Villemin E, Tafti M, Billiard M. Source: Electroencephalography and Clinical Neurophysiology. 1998 August; 107(2): 122-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751283&dopt=Abstract

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Homovanillic acid and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid after total and REM sleep deprivation in humans. Author(s): Livrea P, Di Reda L, Puca FM, Genco S, Specchio LM, Papagno G. Source: European Neurology. 1977; 16(1-6): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=210022&dopt=Abstract

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Hormonal responses to exercise after partial sleep deprivation and after a hypnotic drug-induced sleep. Author(s): Mougin F, Bourdin H, Simon-Rigaud ML, Nguyen NU, Kantelip JP, Davenne D. Source: Journal of Sports Sciences. 2001 February; 19(2): 89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217014&dopt=Abstract

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How sleep deprivation affects gene expression in the brain: a review of recent findings. Author(s): Cirelli C. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 January; 92(1): 394400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744682&dopt=Abstract

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How sleep deprivation affects psychological variables related to college students' cognitive performance. Author(s): Pilcher JJ, Walters AS. Source: Journal of American College Health : J of Ach. 1997 November; 46(3): 121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9394089&dopt=Abstract

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How to preserve the antidepressive effect of sleep deprivation: A comparison of sleep phase advance and sleep phase delay. Author(s): Riemann D, Konig A, Hohagen F, Kiemen A, Voderholzer U, Backhaus J, Bunz J, Wesiack B, Hermle L, Berger M. Source: European Archives of Psychiatry and Clinical Neuroscience. 1999; 249(5): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10591988&dopt=Abstract

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hPP and gastrin response to a liquid meal and oral glucose during prolonged severe exercise, caloric deficit, and sleep deprivation. Author(s): Oektedalen O, Flaten O, Opstad PK, Myren J. Source: Scandinavian Journal of Gastroenterology. 1982 August; 17(5): 619-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7178825&dopt=Abstract

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Human sleep spindle characteristics after sleep deprivation. Author(s): Knoblauch V, Martens WL, Wirz-Justice A, Cajochen C. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 December; 114(12): 2258-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652085&dopt=Abstract

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Hypothalamo-pituitary-adrenal axis activity is related to the level of central arousal: effect of sleep deprivation on the association of high-frequency waking electroencephalogram with cortisol release. Author(s): Chapotot F, Buguet A, Gronfier C, Brandenberger G. Source: Neuroendocrinology. 2001 May; 73(5): 312-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399904&dopt=Abstract

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Impairment of driving performance caused by sleep deprivation or alcohol: a comparative study. Author(s): Fairclough SH, Graham R. Source: Hum Factors. 1999 March; 41(1): 118-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10354808&dopt=Abstract

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Implications of sleep deprivation experiments for our understanding of sleep homeostasis. Author(s): Benington JH, Heller HC. Source: Sleep. 1999 December 15; 22(8): 1033-43. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617164&dopt=Abstract

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Increase in amino acids in the pons after sleep deprivation: a pilot study using proton magnetic resonance spectroscopy. Author(s): Murck H, Struttmann T, Czisch M, Wetter T, Steiger A, Auer DP. Source: Neuropsychobiology. 2002; 45(3): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979059&dopt=Abstract

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Increased cerebral response during a divided attention task following sleep deprivation. Author(s): Drummond SP, Gillin JC, Brown GG. Source: Journal of Sleep Research. 2001 June; 10(2): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422722&dopt=Abstract

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Increased limbic blood flow and total sleep deprivation in major depression with melancholia. Author(s): Ebert D, Feistel H, Barocka A, Kaschka W. Source: Psychiatry Research. 1994 June; 55(2): 101-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711798&dopt=Abstract

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Increased responsiveness to apomorphine after REM sleep deprivation: supersensitivity of dopamine receptors or increase in dopamine turnover? Author(s): Tufik S. Source: The Journal of Pharmacy and Pharmacology. 1981 November; 33(11): 732-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6118415&dopt=Abstract

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Individual differences in subjective and objective alertness during sleep deprivation are stable and unrelated. Author(s): Leproult R, Colecchia EF, Berardi AM, Stickgold R, Kosslyn SM, Van Cauter E. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003 February; 284(2): R280-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529281&dopt=Abstract

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Infant stress and sleep deprivation as an aetiological basis for the sudden infant death syndrome. Author(s): Simpson JM. Source: Early Human Development. 2001 February; 61(1): 1-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172974&dopt=Abstract

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Influence of a functional polymorphism within the angiotensin I-converting enzyme gene on partial sleep deprivation in patients with major depression. Author(s): Baghai TC, Schule C, Zwanzger P, Zill P, Ella R, Eser D, Deiml T, Minov C, Rupprecht R, Bondy B. Source: Neuroscience Letters. 2003 March 27; 339(3): 223-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633893&dopt=Abstract

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Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression. Author(s): Benedetti F, Serretti A, Colombo C, Campori E, Barbini B, di Bella D, Smeraldi E. Source: The American Journal of Psychiatry. 1999 September; 156(9): 1450-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10484962&dopt=Abstract

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Influence of locus of control on mood state disturbance after short-term sleep deprivation. Author(s): Hill DW, Welch JE, Godfrey JA 3rd. Source: Sleep. 1996 January; 19(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8650462&dopt=Abstract

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Influence of sleep deprivation and auditory intensity on reaction time and response force. Author(s): Wlodarczyk D, Jaskowski P, Nowik A. Source: Percept Mot Skills. 2002 June; 94(3 Pt 2): 1101-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186231&dopt=Abstract

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Influence of sleep deprivation on learning among surgical house staff and medical students. Author(s): Browne BJ, Van Susteren T, Onsager DR, Simpson D, Salaymeh B, Condon RE. Source: Surgery. 1994 May; 115(5): 604-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8178259&dopt=Abstract

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Influence of sleep deprivation on neuroactive steroids in major depression. Author(s): Schule C, di Michele F, Baghai T, Romeo E, Bernardi G, Zwanzger P, Padberg F, Pasini A, Rupprecht R. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 March; 28(3): 577-81. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629540&dopt=Abstract

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Interactive effects of sleep deprivation, time of day, and driving experience on a driving task. Author(s): Lenne MG, Triggs TJ, Redman JR. Source: Sleep. 1998; 21(1): 38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9485531&dopt=Abstract

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Interest of modafinil, a new psychostimulant, during a sixty-hour sleep deprivation experiment. Author(s): Lagarde D, Batejat D, Van Beers P, Sarafian D, Pradella S. Source: Fundamental & Clinical Pharmacology. 1995; 9(3): 271-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7557823&dopt=Abstract

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Interhemispheric asymmetry of human sleep EEG in response to selective slow-wave sleep deprivation. Author(s): Ferrara M, De Gennaro L, Curcio G, Cristiani R, Bertini M. Source: Behavioral Neuroscience. 2002 December; 116(6): 976-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492296&dopt=Abstract

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Interleukine-6 serum levels correlate with response to antidepressant sleep deprivation and sleep phase advance. Author(s): Benedetti F, Lucca A, Brambilla F, Colombo C, Smeraldi E. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452541&dopt=Abstract

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Is pre-attentive processing compromised by prolonged wakefulness? Effects of total sleep deprivation on the mismatch negativity. Author(s): Raz A, Deouell LY, Bentin S. Source: Psychophysiology. 2001 September; 38(5): 787-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577902&dopt=Abstract

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Is the antidepressive effect of sleep deprivation stabilized by a three day phase advance of the sleep period? A pilot study. Author(s): Voderholzer U, Valerius G, Schaerer L, Riemann D, Giedke H, Schwarzler F, Berger M, Wiegand M. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 April; 253(2): 68-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799743&dopt=Abstract

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Legal considerations of sleep deprivation among resident physicians. Author(s): Patton DV, Landers DR, Agarwal IT. Source: J Health Law. 2001 Summer; 34(3): 377-417. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571893&dopt=Abstract

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Letter: Combined sleep deprivation and clomipramine in primary depression. Author(s): Loosen PT, Merkel U, Amelung U. Source: Lancet. 1976 July 17; 2(7977): 156-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=59234&dopt=Abstract

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Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. Author(s): Dinges DF, Douglas SD, Zaugg L, Campbell DE, McMann JM, Whitehouse WG, Orne EC, Kapoor SC, Icaza E, Orne MT. Source: The Journal of Clinical Investigation. 1994 May; 93(5): 1930-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7910171&dopt=Abstract

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Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study. Author(s): Szuba MP, Baxter LR Jr, Altshuler LL, Allen EM, Guze BH, Schwartz JM, Liston EH. Source: Psychiatry Research. 1994 March; 51(3): 283-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8208874&dopt=Abstract

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Local sweating responses during recovery sleep after sleep deprivation in humans. Author(s): Dewasmes G, Bothorel B, Nicolas A, Candas V, Libert JP, Ehrhart J, Muzet A. Source: European Journal of Applied Physiology and Occupational Physiology. 1994; 68(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8194539&dopt=Abstract

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Long distance driving and self-induced sleep deprivation among automobile drivers. Author(s): Philip P, Taillard J, Guilleminault C, Quera Salva MA, Bioulac B, Ohayon M. Source: Sleep. 1999 June 15; 22(4): 475-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389223&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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Long-term sleep deprivation as a game. The wear and tear of wakefulness. Author(s): Kamphuisen HA, Kemp B, Kramer CG, Duijvestijn J, Ras L, Steens J. Source: Clinical Neurology and Neurosurgery. 1992; 94 Suppl: S96-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1320535&dopt=Abstract

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Low-dimensional dynamic self-organization in delta-sleep: effect of partial sleep deprivation. Author(s): Cerf R, Sefrioui M, Toussaint M, Luthringer R, Macher JP. Source: Biological Cybernetics. 1996 May; 74(5): 395-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8991455&dopt=Abstract

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Lymphocyte and granulocyte reactions during sleep deprivation. Author(s): Palmblad J, Petrini B, Wasserman J, Akerstedt T. Source: Psychosomatic Medicine. 1979 June; 41(4): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=482523&dopt=Abstract

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Magnetic fields mimic the behavioral effects of REM sleep deprivation in humans. Author(s): Sandyk R, Tsagas N, Anninos PA, Derpapas K. Source: The International Journal of Neuroscience. 1992 July-August; 65(1-4): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1341692&dopt=Abstract

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Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine. Author(s): Wesensten NJ, Belenky G, Kautz MA, Thorne DR, Reichardt RM, Balkin TJ. Source: Psychopharmacology. 2002 January; 159(3): 238-47. Epub 2001 October 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862356&dopt=Abstract

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Maintenance of antidepressant effect of sleep deprivation with the help of lithium. Author(s): Grube M, Hartwich P. Source: European Archives of Psychiatry and Clinical Neuroscience. 1990; 240(1): 60-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2147906&dopt=Abstract

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Maintenance of therapeutic effects of total sleep deprivation by limitation of subsequent sleep. A pilot study. Author(s): van Bemmel AL, van den Hoofdakker RH. Source: Acta Psychiatrica Scandinavica. 1981 May; 63(5): 453-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7032222&dopt=Abstract

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Mania following sleep deprivation. Author(s): Wright JB. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1993 November; 163: 679-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8298841&dopt=Abstract

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Maximal aerobic exercise following prolonged sleep deprivation. Author(s): Goodman J, Radomski M, Hart L, Plyley M, Shephard RJ. Source: International Journal of Sports Medicine. 1989 December; 10(6): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2628360&dopt=Abstract

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Melatonin excretion, body temperature and subjective arousal during 64 hours of sleep deprivation. Author(s): Akerstedt T, Froberg JE, Friberg Y, Wetterberg L. Source: Psychoneuroendocrinology. 1979 July; 4(3): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=515290&dopt=Abstract

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Meta-analysis of the relationship between total sleep deprivation and performance. Author(s): Koslowsky M, Babkoff H. Source: Chronobiology International. 1992 April; 9(2): 132-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1533178&dopt=Abstract

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Metabolic reflection of sleep deprivation. Author(s): Kuhn E, Brodan V, Brodanova M, Rysanek K. Source: Act Nerv Super (Praha). 1969; 11(3): 165-74. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5798779&dopt=Abstract

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Methods for research on sleep deprivation and sleep function. Author(s): Wilkinson RT. Source: Int Psychiatry Clin. 1970; 7(2): 369-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4316519&dopt=Abstract

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MHPG excretion during sleep deprivation in endogenous depression. Author(s): Matussek N, Romisch P, Ackenheil M. Source: Neuropsychobiology. 1977; 3(1): 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=895995&dopt=Abstract

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Microsleep during partial sleep deprivation in depression. Author(s): Hemmeter U, Bischof R, Hatzinger M, Seifritz E, Holsboer-Trachsler E. Source: Biological Psychiatry. 1998 June 1; 43(11): 829-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9611673&dopt=Abstract

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Moderate exercise and hemodilution during sleep deprivation. Author(s): Goodman JM, Plyley MJ, Hart LE, Radomski M, Shephard RJ. Source: Aviation, Space, and Environmental Medicine. 1990 February; 61(2): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2310361&dopt=Abstract

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Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication. Author(s): Williamson AM, Feyer AM. Source: Occupational and Environmental Medicine. 2000 October; 57(10): 649-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984335&dopt=Abstract

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Modification of the scopolamine effect by sleep deprivation. Author(s): Hort V, Vojtechovsky M, Brezinova V, Soukupova B, Safratova V. Source: Act Nerv Super (Praha). 1970 January 12; 12(1): 53-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5418659&dopt=Abstract

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Monoamine oxidase activity in platelets before and after sleep deprivation as predictor for antidepressive drug response. Author(s): Fahndrich E, Muller-Oerlinghausen B. Source: Mod Probl Pharmacopsychiatry. 1983; 19: 327-36. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6865972&dopt=Abstract

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Monotonic and rhythmic influences: a challenge for sleep deprivation research. Author(s): Babkoff H, Caspy T, Mikulincer M, Sing HC. Source: Psychological Bulletin. 1991 May; 109(3): 411-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2062980&dopt=Abstract

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Motor reactivity, pain threshold and effects of sleep deprivation in unipolar depressives. Author(s): Bezzi G, Pinelli P, Tosca P. Source: Psychiatr Clin (Basel). 1981; 14(3): 150-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7330254&dopt=Abstract

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Myocardial infarction during sleep deprivation in a patient with dextrocardia--a case report. Author(s): Delva NJ, Woo M, Southmayd SE, Hawken ER. Source: Angiology. 2001 January; 52(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11205938&dopt=Abstract

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Nap polygraphic recordings after partial sleep deprivation in patients with suspected epileptic seizures. Author(s): Peraita-Adrados R, Gutierrez-Solana L, Ruiz-Falco ML, Garcia-Penas JJ. Source: Neurophysiologie Clinique = Clinical Neurophysiology. 2001 February; 31(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281068&dopt=Abstract

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Naps after total sleep deprivation in depressed patients: are they depressiogenic? Author(s): Riemann D, Wiegand M, Lauer CJ, Berger M. Source: Psychiatry Research. 1993 November; 49(2): 109-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8153186&dopt=Abstract

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Naps and modafinil as countermeasures for the effects of sleep deprivation on cognitive performance. Author(s): Batejat DM, Lagarde DP. Source: Aviation, Space, and Environmental Medicine. 1999 May; 70(5): 493-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332946&dopt=Abstract

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Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity. Author(s): Thomas M, Sing H, Belenky G, Holcomb H, Mayberg H, Dannals R, Wagner H, Thorne D, Popp K, Rowland L, Welsh A, Balwinski S, Redmond D. Source: Journal of Sleep Research. 2000 December; 9(4): 335-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11123521&dopt=Abstract

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Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation. Author(s): Ebert D, Berger M. Source: Psychopharmacology. 1998 November; 140(1): 1-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862396&dopt=Abstract

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Neuroendocrine and neurochemical consequences of long-term sleep deprivation in rats: similarities to some features of depression. Author(s): Patchev V, Felszeghy K, Koranyi L. Source: Homeost Health Dis. 1991 October; 33(3): 97-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1818684&dopt=Abstract

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Neuroendocrinological investigations during sleep deprivation in depression. I. Early morning levels of thyrotropin, TH, cortisol, prolactin, LH, FSH, estradiol, and testosterone. Author(s): Baumgartner A, Graf KJ, Kurten I, Meinhold H, Scholz P. Source: Biological Psychiatry. 1990 October 1; 28(7): 556-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2121292&dopt=Abstract

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Neuroendocrinological investigations during sleep deprivation in depression. II. Longitudinal measurement of thyrotropin, TH, cortisol, prolactin, GH, and LH during sleep and sleep deprivation. Author(s): Baumgartner A, Riemann D, Berger M. Source: Biological Psychiatry. 1990 October 1; 28(7): 569-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2171684&dopt=Abstract

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Neurological findings following short-term sleep deprivation. Author(s): Sassin JF. Source: Archives of Neurology. 1970 January; 22(1): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5409601&dopt=Abstract

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Nineteen-hour variation of postural sway, alertness and rectal temperature during sleep deprivation. Author(s): Nakano T, Araki K, Michimori A, Inbe H, Hagiwara H, Koyama E. Source: Psychiatry and Clinical Neurosciences. 2001 June; 55(3): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422874&dopt=Abstract

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Nitrogen metabolism in the CNS after paradoxical sleep deprivation in rats. Author(s): Dostalova K, Navratil J, Sklenovsky A. Source: Act Nerv Super (Praha). 1978 February; 20(1): 57-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=205076&dopt=Abstract

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No Influence of a functional polymorphism within the serotonin transporter gene on partial sleep deprivation in major depression. Author(s): Baghai TC, Schule C, Zwanzger P, Zill P, Ella R, Eser D, Deiml T, Minov C, Rupprecht R, Bondy B. Source: World J Biol Psychiatry. 2003 July; 4(3): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872203&dopt=Abstract

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Nocturnal TSH and prolactin secretion during sleep deprivation and prediction of antidepressant response in patients with major depression. Author(s): Kasper S, Sack DA, Wehr TA, Kick H, Voll G, Vieira A. Source: Biological Psychiatry. 1988 October; 24(6): 631-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3167147&dopt=Abstract

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Non-rapid-eye-movement sleep propensity after sleep deprivation in human subjects. Author(s): Tagaya H, Uchiyama M, Shibui K, Kim K, Suzuki H, Kamei Y, Okawa M. Source: Neuroscience Letters. 2002 April 19; 323(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911980&dopt=Abstract

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Nursing intensive care group journal. 2. Sleep deprivation. Author(s): Morgan H, White B. Source: Nurs Mirror. 1983 October 5; 157(14): S8-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6556603&dopt=Abstract

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Observed behavior as a predictor of the response to sleep deprivation in depressed patients. Author(s): Bouhuys AL, Beersma DG, van den Hoofdakker RH. Source: Psychiatry Research. 1989 April; 28(1): 47-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2740467&dopt=Abstract

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Oculomotor impairment after 1 night of total sleep deprivation: a dissociation between measures of speed and accuracy. Author(s): De Gennaro L, Ferrara M, Urbani L, Bertini M. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 October; 111(10): 1771-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11018491&dopt=Abstract

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Oculomotor impairment during chronic partial sleep deprivation. Author(s): Russo M, Thomas M, Thorne D, Sing H, Redmond D, Rowland L, Johnson D, Hall S, Krichmar J, Balkin T. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 April; 114(4): 723-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686280&dopt=Abstract

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One night of total sleep deprivation impairs implicit learning in the serial reaction task, but not the behavioral expression of knowledge. Author(s): Heuer H, Klein W. Source: Neuropsychology. 2003 July; 17(3): 507-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959516&dopt=Abstract

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Ongoing lithium treatment prevents relapse after total sleep deprivation. Author(s): Benedetti F, Colombo C, Barbini B, Campori E, Smeraldi E. Source: Journal of Clinical Psychopharmacology. 1999 June; 19(3): 240-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350030&dopt=Abstract

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Overnight human plasma melatonin, cortisol, prolactin, TSH, under conditions of normal sleep, sleep deprivation, and sleep recovery. Author(s): von Treuer K, Norman TR, Armstrong SM. Source: Journal of Pineal Research. 1996 January; 20(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8648563&dopt=Abstract

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Parsing attentional components during a simple reaction time task using sleep deprivation and amphetamine intervention. Author(s): Cochran JC, Thorne DR, Penetar DM, Newhouse PA. Source: Percept Mot Skills. 1992 December; 75(3 Pt 1): 675-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1454457&dopt=Abstract

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Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. Author(s): Irwin M, McClintick J, Costlow C, Fortner M, White J, Gillin JC. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1996 April; 10(5): 643-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8621064&dopt=Abstract

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Partial sleep deprivation reduces natural killer cell activity in humans. Author(s): Irwin M, Mascovich A, Gillin JC, Willoughby R, Pike J, Smith TL. Source: Psychosomatic Medicine. 1994 November-December; 56(6): 493-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871104&dopt=Abstract

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Partial sleep deprivation to prevent 48-hour mood cycles. Author(s): Churchill CM, Dilsaver SC. Source: Acta Psychiatrica Scandinavica. 1990 April; 81(4): 398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2343766&dopt=Abstract

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Performance deficits following short-term partial sleep deprivation and subsequent recovery oversleeping. Author(s): Herscovitch J, Broughton R. Source: Can J Psychol. 1981 December; 35(4): 309-22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7337884&dopt=Abstract

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Phosphorous31 magnetic resonance spectroscopy after total sleep deprivation in healthy adult men. Author(s): Dorsey CM, Lukas SE, Moore CM, Tartarini WL, Parow AM, Villafuerte RA, Renshaw PF. Source: Sleep. 2003 August 1; 26(5): 573-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938810&dopt=Abstract

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Physical activity and posture: influence on TSH and thyroid hormones during sleep deprivation. Author(s): Baumgartner A, Sucher N. Source: Psychiatry Research. 1990 November; 34(2): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2287650&dopt=Abstract

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Physical signs associated with excessive television-game playing and sleep deprivation. Author(s): Tazawa Y, Okada K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 December; 43(6): 647-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737743&dopt=Abstract

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Plasma catecholamines and selective slow wave sleep deprivation. Author(s): Tiemeier H, Pelzer E, Jonck L, Moller HJ, Rao ML. Source: Neuropsychobiology. 2002; 45(2): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893864&dopt=Abstract

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Platelet serotonin and interleukin-1 beta after sleep deprivation and recovery sleep in humans. Author(s): Heiser P, Dickhaus B, Opper C, Schreiber W, Clement HW, Hasse C, Hennig J, Krieg JC, Wesemann W. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1997; 104(10): 1049-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9503257&dopt=Abstract

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Poor recovery sleep after sleep deprivation in delayed sleep phase syndrome. Author(s): Uchiyama M, Okawa M, Shibui K, Kim K, Kudo Y, Hayakawa T, Kamei Y, Urata J. Source: Psychiatry and Clinical Neurosciences. 1999 April; 53(2): 195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10459687&dopt=Abstract

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Postural control, attention and sleep deprivation. Author(s): Schlesinger A, Redfern MS, Dahl RE, Jennings JR. Source: Neuroreport. 1998 January 5; 9(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9592046&dopt=Abstract

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Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex. Author(s): Wu J, Buchsbaum MS, Gillin JC, Tang C, Cadwell S, Wiegand M, Najafi A, Klein E, Hazen K, Bunney WE Jr, Fallon JH, Keator D. Source: The American Journal of Psychiatry. 1999 August; 156(8): 1149-58. Erratum In: Am J Psychiatry 1999 October; 156(10): 1666. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10450253&dopt=Abstract

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Prediction of response to total sleep deprivation by autonomic heart rate parameters? Author(s): Rechlin T, Hegmann H, Weis M, Stemmler M, Claus D, Kaschka WP. Source: Biological Psychiatry. 1995 February 15; 37(4): 280-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7711168&dopt=Abstract

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Prediction of sleep deprivation outcome by diurnal variation of mood. Author(s): Haug HJ. Source: Biological Psychiatry. 1992 February 1; 31(3): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1547300&dopt=Abstract

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Prediction of the antidepressant response to total sleep deprivation by diurnal variation of mood. Author(s): Reinink E, Bouhuys N, Wirz-Justice A, van den Hoofdakker R. Source: Psychiatry Research. 1990 May; 32(2): 113-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2367598&dopt=Abstract

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Prediction of the antidepressant response to total sleep deprivation of depressed patients: longitudinal versus single day assessment of diurnal mood variation. Author(s): Reinink E, Bouhuys AL, Gordijn MC, Van Den Hoofdakker RH. Source: Biological Psychiatry. 1993 October 1; 34(7): 471-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8268332&dopt=Abstract

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Prefrontal neuropsychological effects of sleep deprivation in young adults--a model for healthy aging? Author(s): Harrison Y, Horne JA, Rothwell A. Source: Sleep. 2000 December 15; 23(8): 1067-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145321&dopt=Abstract

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Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation. Author(s): Clark C, Dupont R, Golshan S, Gillin JC, Rapaport MH, Kelsoe JR. Source: Journal of Affective Disorders. 2000 July; 59(1): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10814775&dopt=Abstract

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Prolactin response to sulpiride before and after sleep deprivation in depression. Author(s): Ebert D, Kaschka W, Stegbauer P, Schrell U. Source: Biological Psychiatry. 1993 April 15-May 1; 33(8-9): 666-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8329499&dopt=Abstract

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Quantitative analysis of the effects of slow wave sleep deprivation during the first 3 h of sleep on subsequent EEG power density. Author(s): Dijk DJ, Beersma DG, Daan S, Bloem GM, Van den Hoofdakker RH. Source: Eur Arch Psychiatry Neurol Sci. 1987; 236(6): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3678290&dopt=Abstract

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Rapid eye movement sleep deprivation as a probe in elderly subjects. Author(s): Reynolds CF 3rd, Buysse DJ, Kupfer DJ, Hoch CC, Houck PR, Matzzie J, George CJ. Source: Archives of General Psychiatry. 1990 December; 47(12): 1128-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2244798&dopt=Abstract

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Rapid eye movement sleep deprivation in elderly patients with concurrent symptoms of depression and dementia. Author(s): Buysse DJ, Reynolds CF 3rd, Hoch CC, Houck PR, Berman SR, Matzzie J, Kupfer DJ. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1992 Summer; 4(3): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1498577&dopt=Abstract

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Rate of switch from depression into mania after therapeutic sleep deprivation in bipolar depression. Author(s): Colombo C, Benedetti F, Barbini B, Campori E, Smeraldi E. Source: Psychiatry Research. 1999 June 30; 86(3): 267-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482346&dopt=Abstract

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Recovery sleep and performance following sleep deprivation with dextroamphetamine. Author(s): Caldwell JL, Caldwell JA. Source: Journal of Sleep Research. 1997 June; 6(2): 92-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9377539&dopt=Abstract

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Regional differences of the human sleep electroencephalogram in response to selective slow-wave sleep deprivation. Author(s): Ferrara M, De Gennaro L, Curcio G, Cristiani R, Corvasce C, Bertini M. Source: Cerebral Cortex (New York, N.Y. : 1991). 2002 July; 12(7): 737-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050085&dopt=Abstract

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Relation between responses to repetitive transcranial magnetic stimulation and partial sleep deprivation in major depression. Author(s): Padberg F, Schule C, Zwanzger P, Baghai T, Ella R, Mikhaiel P, Hampel H, Moller HJ, Rupprecht R. Source: Journal of Psychiatric Research. 2002 May-June; 36(3): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886690&dopt=Abstract

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Relations between depressed mood and vocal parameters before, during and after sleep deprivation: a circadian rhythm study. Author(s): Bouhuys AL, Schutte HK, Beersma DG, Nieboer GL. Source: Journal of Affective Disorders. 1990 August; 19(4): 249-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2146301&dopt=Abstract

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Relationships between thyroid hormone and antidepressant responses to total sleep deprivation in mood disorder patients. Author(s): Parekh PI, Ketter TA, Altshuler L, Frye MA, Callahan A, Marangell L, Post RM. Source: Biological Psychiatry. 1998 March 1; 43(5): 392-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9513756&dopt=Abstract

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REM sleep deprivation changes behavioral response to catecholaminergic and serotonergic receptor activation in rats. Author(s): Mogilnicka E. Source: Pharmacology, Biochemistry, and Behavior. 1981 July; 15(1): 149-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7197363&dopt=Abstract

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REM sleep deprivation during 5 hours leads to an immediate REM sleep rebound and to suppression of non-REM sleep intensity. Author(s): Beersma DG, Dijk DJ, Blok CG, Everhardus I. Source: Electroencephalography and Clinical Neurophysiology. 1990 August; 76(2): 11422. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1697239&dopt=Abstract

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REM sleep deprivation suppresses acquisition of classical eyeblink conditioning. Author(s): Ohno H, Urushihara R, Sei H, Morita Y. Source: Sleep. 2002 Dec15; 25(8): 877-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489894&dopt=Abstract

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Repeated partial sleep deprivation progressively changes in EEG during sleep and wakefulness. Author(s): Brunner DP, Dijk DJ, Borbely AA. Source: Sleep. 1993 February; 16(2): 100-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8446828&dopt=Abstract

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Repeated sleep deprivation once versus twice a week in combination with amitriptyline. Author(s): Kuhs H, Kemper B, Lippe-Neubauer U, Meyer-Dunker J, Tolle R. Source: Journal of Affective Disorders. 1998 January; 47(1-3): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9476749&dopt=Abstract

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Resident stress: sleep deprivation. Author(s): Dilts PV Jr. Source: Academic Medicine : Journal of the Association of American Medical Colleges. 1989 January; 64(1): 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2914057&dopt=Abstract

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Response covariation of escape-maintained aberrant behavior correlated with sleep deprivation. Author(s): Oreilly MF, Lancioni G. Source: Research in Developmental Disabilities. 2000 March-April; 21(2): 125-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817419&dopt=Abstract

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Response to sleep deprivation in three women with postpartum psychosis. Author(s): Strouse TB, Szuba MP, Baxter LR Jr. Source: The Journal of Clinical Psychiatry. 1992 June; 53(6): 204-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1607349&dopt=Abstract

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Response to total sleep deprivation and clomipramine in endogenous depression. Author(s): Elsenga S, Van den Hoofdakker RH. Source: Journal of Psychiatric Research. 1987; 21(2): 151-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3585805&dopt=Abstract

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Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study. Author(s): Kasper S, Voll G, Vieira A, Kick H. Source: Pharmacopsychiatry. 1990 May; 23(3): 135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2115680&dopt=Abstract

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Response-stimulus interval in choice serial reaction time: interaction with sleep deprivation, choice, and practice. Author(s): Wilkinson RT. Source: The Quarterly Journal of Experimental Psychology. A, Human Experimental Psychology. 1990 May; 42(2): 401-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2367685&dopt=Abstract

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RO 15-1788 decreases hypnotic effects of sleep deprivation. Author(s): Lavie P. Source: Life Sciences. 1987 July 13; 41(2): 227-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3110524&dopt=Abstract

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Seasonal effects of sleep deprivation on thermoregulatory responses in a hot environment. Author(s): Fujita M, Lee D, Ismail MS, Tochihara Y. Source: Journal of Physiological Anthropology and Applied Human Science. 2003 November; 22(6): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14646261&dopt=Abstract

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Seizure associated with sleep deprivation and sustained-release bupropion. Author(s): Oncken CA, Duckrow RB. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745515&dopt=Abstract

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Selective slow-wave sleep deprivation influences blood serotonin profiles and serum melatonin concentrations in healthy subjects. Author(s): Rao ML, Pelzer E, Papassotiropoulos A, Tiemeier H, Jonck L, Moller HJ. Source: Biological Psychiatry. 1996 October 1; 40(7): 664-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8886302&dopt=Abstract

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Serum prolactin, growth hormone, total corticoids, thyroid hormones and thyrotropine during serial therapeutic sleep deprivation. Author(s): Kuhs H, Farber D, Tolle R. Source: Biological Psychiatry. 1996 May 15; 39(10): 857-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172706&dopt=Abstract

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Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation--preliminary results. Author(s): Ebert D, Feistel H, Kaschka W, Barocka A, Pirner A. Source: Biological Psychiatry. 1994 June 1; 35(11): 880-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8054411&dopt=Abstract

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Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment--neurobiological and psychometric assessment of course. Author(s): Holsboer-Trachsler E, Hemmeter U, Hatzinger M, Seifritz E, Gerhard U, Hobi V. Source: Journal of Psychiatric Research. 1994 July-August; 28(4): 381-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7877117&dopt=Abstract

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Sleep deprivation and human immune function. Author(s): Dinges DF, Douglas SD, Hamarman S, Zaugg L, Kapoor S. Source: Advances in Neuroimmunology. 1995; 5(2): 97-110. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7496616&dopt=Abstract

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Sleep deprivation and performance. Author(s): Price SR. Source: Anaesthesia. 2003 December; 58(12): 1238-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14705694&dopt=Abstract

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Sleep deprivation and thyroid hormones. Author(s): Szuba MP, Baxter LR Jr. Source: Psychiatry Research. 1994 July; 53(1): 107-8; Author Reply 109-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7991728&dopt=Abstract

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Sleep deprivation combined with consecutive sleep phase advance as a fast-acting therapy in depression: an open pilot trial in medicated and unmedicated patients. Author(s): Berger M, Vollmann J, Hohagen F, Konig A, Lohner H, Voderholzer U, Riemann D. Source: The American Journal of Psychiatry. 1997 June; 154(6): 870-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9167521&dopt=Abstract

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Sleep deprivation does not induce sister chromatid exchange in humans. Author(s): Jagdt B, Warncke K, Auer H, Rudiger HW. Source: Mutation Research. 1996 September 26; 361(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8816937&dopt=Abstract

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Sleep deprivation hastens the antidepressant action of fluoxetine. Author(s): Benedetti F, Barbini B, Lucca A, Campori E, Colombo C, Smeraldi E. Source: European Archives of Psychiatry and Clinical Neuroscience. 1997; 247(2): 100-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9177956&dopt=Abstract

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Sleep deprivation in critical care units. Author(s): Honkus VL. Source: Critical Care Nursing Quarterly. 2003 July-September; 26(3): 179-89; Quiz 190-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930033&dopt=Abstract

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Sleep deprivation influences some but not all processes of supervisory attention. Author(s): Jennings JR, Monk TH, van der Molen MW. Source: Psychological Science : a Journal of the American Psychological Society / Aps. 2003 September; 14(5): 473-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930479&dopt=Abstract

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Sleep deprivation: effects on work capacity, self-paced walking, contractile properties and perceived exertion. Author(s): Rodgers CD, Paterson DH, Cunningham DA, Noble EG, Pettigrew FP, Myles WS, Taylor AW. Source: Sleep. 1995 January; 18(1): 30-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7761740&dopt=Abstract

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Sleep electroencephalogram in seasonal affective disorder and in control women: effects of midday light treatment and sleep deprivation. Author(s): Brunner DP, Krauchi K, Dijk DJ, Leonhardt G, Haug HJ, Wirz-Justice A. Source: Biological Psychiatry. 1996 September 15; 40(6): 485-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8879468&dopt=Abstract

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Sleep latency measures of caffeine effects during sleep deprivation. Author(s): Kelly TL, Mitler MM, Bonnet MH. Source: Electroencephalography and Clinical Neurophysiology. 1997 May; 102(5): 397400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9191583&dopt=Abstract

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Sleep, sleep deprivation and infectious disease: studies in animals. Author(s): Toth LA. Source: Advances in Neuroimmunology. 1995; 5(1): 79-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7795895&dopt=Abstract

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Sleepiness, performance, and neuroendocrine function during sleep deprivation: effects of exposure to bright light or exercise. Author(s): Leproult R, Van Reeth O, Byrne MM, Sturis J, Van Cauter E. Source: Journal of Biological Rhythms. 1997 June; 12(3): 245-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9181436&dopt=Abstract

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Some measures to reduce effects of prolonged sleep deprivation. Author(s): Lagarde D, Batejat D. Source: Neurophysiologie Clinique = Clinical Neurophysiology. 1995; 25(6): 376-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8904200&dopt=Abstract

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Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects. Author(s): Parry BL, LeVeau B, Mostofi N, Naham HC, Loving R, Clopton P, Gillin JC. Source: Journal of Biological Rhythms. 1997 February; 12(1): 34-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9104689&dopt=Abstract

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The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Author(s): Van Dongen HP, Maislin G, Mullington JM, Dinges DF. Source: Sleep. 2003 March 15; 26(2): 117-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683469&dopt=Abstract

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The cyclic alternating pattern decreases as a consequence of total sleep deprivation and correlates with EEG arousals. Author(s): De Gennaro L, Ferrara M, Spadini V, Curcio G, Cristiani R, Bertini M. Source: Neuropsychobiology. 2002; 45(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893866&dopt=Abstract

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The diagnostic yield of a second EEG after partial sleep deprivation: a prospective study in children with newly diagnosed seizures. Author(s): Carpay JA, de Weerd AW, Schimsheimer RJ, Stroink H, Brouwer OF, Peters AC, van Donselaar CA, Geerts AT, Arts WF. Source: Epilepsia. 1997 May; 38(5): 595-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9184606&dopt=Abstract

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The effect of sleep deprivation on sleep states, breathing events, peripheral chemoresponsiveness and arousal propensity in healthy 3 month old infants. Author(s): Thomas DA, Poole K, McArdle EK, Goodenough PC, Thompson J, Beardsmore CS, Simpson H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1996 May; 9(5): 932-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793454&dopt=Abstract

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The effect of total sleep deprivation on cognitive functions in normal adult male subjects. Author(s): Kim DJ, Lee HP, Kim MS, Park YJ, Go HJ, Kim KS, Lee SP, Chae JH, Lee CT. Source: The International Journal of Neuroscience. 2001 July; 109(1-2): 127-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11699337&dopt=Abstract

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The effects of total sleep deprivation on cerebral responses to cognitive performance. Author(s): Drummond SP, Brown GG. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 November; 25(5 Suppl): S68-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682277&dopt=Abstract

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The night float paradigm to decrease sleep deprivation: good solution or a new problem? Author(s): Cavallo A, Ris MD, Succop P. Source: Ergonomics. 2003 June 10; 46(7): 653-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745679&dopt=Abstract

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The relationship between selective sleep deprivation, nocturnal jaw-muscle activity and pain in healthy men. Author(s): Arima T, Svensson P, Rasmussen C, Nielsen KD, Drewes AM, ArendtNielsen L. Source: Journal of Oral Rehabilitation. 2001 February; 28(2): 140-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298262&dopt=Abstract

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The relationship between sleep deprivation and the nocturnal decline of blood pressure. Author(s): Rosansky SJ, Menachery SJ, Whittman D, Rosenberg JC. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1996 November; 9(11): 1136-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8931841&dopt=Abstract

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The role of activation in the effect of total sleep deprivation on depressed mood. Author(s): Beutler LE, Cano MC, Miro E, Buela-Casal G. Source: Journal of Clinical Psychology. 2003 March; 59(3): 369-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579552&dopt=Abstract

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The value of sleep deprivation as a diagnostic tool in adult sleepwalkers. Author(s): Joncas S, Zadra A, Paquet J, Montplaisir J. Source: Neurology. 2002 March 26; 58(6): 936-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914411&dopt=Abstract

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Therapeutic use of sleep deprivation in depression. Author(s): Giedke H, Schwarzler F. Source: Sleep Medicine Reviews. 2002 October; 6(5): 361-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531127&dopt=Abstract

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Time course of reaction time and EEG while performing a vigilance task during total sleep deprivation. Author(s): Corsi-Cabrera M, Arce C, Ramos J, Lorenzo I, Guevara MA. Source: Sleep. 1996 September; 19(7): 563-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8899935&dopt=Abstract

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Time estimation during prolonged sleep deprivation and its relation to activation measures. Author(s): Miro E, Cano MC, Espinosa-Fernandez L, Buela-Casal G. Source: Hum Factors. 2003 Spring; 45(1): 148-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916587&dopt=Abstract

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Timing is everything: does the robust upregulation of noradrenergically regulated plasticity genes underlie the rapid antidepressant effects of sleep deprivation? Author(s): Payne JL, Quiroz JA, Zarate CA Jr, Manji HK. Source: Biological Psychiatry. 2002 November 15; 52(10): 921-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437933&dopt=Abstract

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Tired surgical trainees. Sleep deprivation affects psychomotor function. Author(s): Williams M. Source: Bmj (Clinical Research Ed.). 2002 May 11; 324(7346): 1154. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003876&dopt=Abstract

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Topographical changes in N1-P2 amplitude upon awakening from recovery sleep after slow-wave sleep deprivation. Author(s): Ferrara M, De Gennaro L, Ferlazzo F, Curcio G, Cristiani R, Bertini M. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 August; 113(8): 1183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139996&dopt=Abstract

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Total sleep deprivation and the thyroid axis: effects of sleep and waking activity. Author(s): Gary KA, Winokur A, Douglas SD, Kapoor S, Zaugg L, Dinges DF. Source: Aviation, Space, and Environmental Medicine. 1996 June; 67(6): 513-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8827131&dopt=Abstract

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Total sleep deprivation induces an acute and transient increase in NK cell activity in healthy young volunteers. Author(s): Matsumoto Y, Mishima K, Satoh K, Tozawa T, Mishima Y, Shimizu T, Hishikawa Y. Source: Sleep. 2001 November 1; 24(7): 804-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683483&dopt=Abstract

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Understanding post operative psychosis and sleep deprivation: a case approach. Author(s): Mirka T, Rukholm E. Source: Can J Cardiovasc Nurs. 1993; 3(4): 3-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8148058&dopt=Abstract

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Urinary melatonin rhythms during sleep deprivation in depressed patients and normals. Author(s): Jimerson DC, Lynch HJ, Post RM, Wurtman RJ, Bunney WE Jr. Source: Life Sciences. 1977 May 1; 20(9): 1501-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=559896&dopt=Abstract

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Urine creatinine excretion: variability and volume dependency during sleep deprivation. Author(s): Rubin RT. Source: Psychosomatic Medicine. 1971 November-December; 33(6): 539-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5148983&dopt=Abstract

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Use of the ERG and EOG in evaluating the effect of sleep deprivation on visual function in flying personnel. Author(s): Tasker DI, Kinel SG, Tredici TJ. Source: Aviation, Space, and Environmental Medicine. 1975 July; 46(7): 943-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1156304&dopt=Abstract

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Variability of the averaged evoked potentials in healthy subjects after 24-hour sleep deprivation. Author(s): Miszczak J, Zuzewicz W. Source: Acta Physiol Pol. 1977 January-February; 28(1): 61-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=868525&dopt=Abstract

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Visual selective attention during meaningful noise and after sleep deprivation. Author(s): Gunter TC, van der Zande RD, Wiethoff M, Mulder G, Mulder LJ. Source: Electroencephalogr Clin Neurophysiol Suppl. 1987; 40: 99-107. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3480212&dopt=Abstract

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Voluntary oculomotor performance upon awakening after total sleep deprivation. Author(s): Ferrara M, De Gennaro MFL, Bertini M. Source: Sleep. 2000 September 15; 23(6): 801-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007447&dopt=Abstract

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What is causing excessive daytime sleepiness? Evaluation to distinguish sleep deprivation from sleep disorders. Author(s): Mahowald MW. Source: Postgraduate Medicine. 2000 March; 107(3): 108-10, 115-8, 123. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728139&dopt=Abstract

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White blood cells and cortisol after sleep deprivation and recovery sleep in humans. Author(s): Heiser P, Dickhaus B, Schreiber W, Clement HW, Hasse C, Hennig J, Remschmidt H, Krieg JC, Wesemann W, Opper C. Source: European Archives of Psychiatry and Clinical Neuroscience. 2000; 250(1): 16-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738860&dopt=Abstract

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Why is sleep deprivation an orphan drug? Author(s): Wirz-Justice A. Source: Psychiatry Research. 1998 November 16; 81(2): 281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9858045&dopt=Abstract

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Worsening of delusional depression after sleep deprivation: case reports. Author(s): Benedetti F, Zanardi R, Colombo C, Smeraldi E. Source: Journal of Psychiatric Research. 1999 January-February; 33(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10094242&dopt=Abstract

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CHAPTER 2. NUTRITION AND SLEEP DEPRIVATION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and sleep deprivation.

Finding Nutrition Studies on Sleep Deprivation 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.4 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 “sleep deprivation” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “sleep deprivation” (or a synonym): •

Atrial natriuretic peptide in plasma after prolonged physical strain, energy deficiency and sleep deprivation. Author(s): Norwegian Defence Research Establishment, Kjeller. Source: Opstad, P K Haugen, A H Sejersted, O M Bahr, R Skrede, K K Eur-J-ApplPhysiol-Occup-Physiol. 1994; 68(2): 122-6 0301-5548

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Caffeine during sleep deprivation: sleep tendency and dynamics of recovery sleep in rats. Author(s): Sleep Disorders Research Center, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA. Source: Wurts, S W Edgar, D M Pharmacol-Biochem-Behavolume 2000 January 1; 65(1): 155-62 0091-3057

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Combination of bright light and caffeine as a countermeasure for impaired alertness and performance during extended sleep deprivation. Author(s): Department of Psychology, Bowling Green State University, Ohio 43403, USA. [email protected] Source: Wright, K P Badia, P Myers, B L Plenzler, S C J-Sleep-Res. 1997 March; 6(1): 2635 0962-1105

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Distinct effects of paradoxical sleep deprivation and cocaine administration on sexual behavior in male rats. Author(s): Department of Psychobiology, Universidade Federal de Sao Paulo, Vila Clementino, Brazil. [email protected] Source: Andersen, M L Tufik, S Addict-Biol. 2002 April; 7(2): 251-3 1355-6215

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Does paradoxical sleep deprivation and cocaine induce penile erection and ejaculation in old rats? Author(s): Department of Psychobiology, Universidade Federal de Sao Paulo, Brazil. [email protected] Source: Andersen, M L Bignotto, M Machado, R B Tufik, S Addict-Biol. 2002 July; 7(3): 285-90 1355-6215

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Effects of adaptogens on granulocytopoiesis during paradoxical sleep deprivation. Author(s): Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences. Source: Provalova, N V Skurikhin, E G Suslov, N I Dygai, A M Gol'dberg, E D Bull-ExpBiol-Med. 2002 March; 133(3): 261-4 0007-4888

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Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation. Author(s): Department of General Psychiatry, Vienna University, Austria. [email protected] Source: Neumeister, A Praschak Rieder, N Hesselmann, B Vitouch, O Rauh, M Barocka, A Tauscher, J Kasper, S Arch-Gen-Psychiatry. 1998 February; 55(2): 167-72 0003-990X

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Efficacy of oral magnesium administration on decreased exercise tolerance in a state of chronic sleep deprivation. Author(s): Second Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. Source: Tanabe, K Yamamoto, A Suzuki, N Osada, N Yokoyama, Y Samejima, H Seki, A Oya, M Murabayashi, T Nakayama, M Yamamoto, M Omiya, K Itoh, H Murayama, M Jpn-Circ-J. 1998 May; 62(5): 341-6 0047-1828

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Hormonal responses to exercise after partial sleep deprivation and after a hypnotic drug-induced sleep. Author(s): UFR STAPS, Laboratoire des Sciences du Sport, Besancon, France. Source: Mougin, F Bourdin, H Simon Rigaud, M L Nguyen, N U Kantelip, J P Davenne, D J-Sports-Sci. 2001 February; 19(2): 89-97 0264-0414

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Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia induced by sleep deprivation. Author(s): Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. [email protected] Source: Everson, Carol A Nowak, Thaddeus S Jr Am-J-Physiol-Endocrinol-Metab. 2002 July; 283(1): E85-93 0193-1849

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Increased dietary fat prevents sleep deprivation-induced immune suppression in rats. Source: Horohov, D.W. Pourciau, S.S. Mistric, L. Chapman, A. Ryan, D.H. Comp-med. Memphis, TN : American Association for Laboratory Animal Science, 2000-. June 2001. volume 51 (3) page 230-233. 1532-0820

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Individual differences in subjective and objective alertness during sleep deprivation are stable and unrelated. Author(s): Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. Source: Leproult, R Colecchia, E F Berardi, A M Stickgold, R Kosslyn, S M Van Cauter, E Am-J-Physiol-Regul-Integr-Comp-Physiol. 2003 February; 284(2): R280-90 0363-6119

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Influence of sleep deprivation coupled with administration of melatonin on the ultrastructure of rat pineal gland. Author(s): Department of Anatomy, Chung-Shan Medical and Dental College, No. 110, Sec. 1, Chien Kuo North Road, Taichung, Taiwan. [email protected] Source: Lan, C T Hsu, J C Ling, E A Brain-Res. 2001 August 10; 910(1-2): 1-11 0006-8993

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Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine. Author(s): Department of Neurobiology and Behaviour, Division of Neuropsychiatry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA. [email protected] Source: Wesensten, Nancy Jo Belenky, Gregory Kautz, Mary A Thorne, David R Reichardt, Rebecca M Balkin, Thomas J Psychopharmacology-(Berl). 2002 January; 159(3): 238-47 0033-3158

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Maintenance of antidepressant effect of sleep deprivation with the help of lithium. Author(s): Department of Psychiatry, Stadtisches Krankenhaus Frankfurt am Main, Federal Republic of Germany. Source: Grube, M Hartwich, P Eur-Arch-Psychiatry-Clin-Neurosci. 1990; 240(1): 60-1 0940-1334

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Mechanisms underling the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation. Author(s): Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences. Source: Provalova, N V Skurikhin, E G Pershina, O V Suslov, N I Minakova, M Y Dygai, A M Gol'dberg, E D Bull-Exp-Biol-Med. 2002 May; 133(5): 428-32 0007-4888

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Melatonin treatment does not prevent decreases in brain glutathione levels induced by sleep deprivation. Author(s): Department of Psychobiology, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil.

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Source: D'Almeida, V Hipolide, D C Lobo, L L de Oliveira, A C Nobrega, J N Tufik, S Eur-J-Pharmacol. 2000 March 3; 390(3): 299-302 0014-2999 •

Ongoing lithium treatment prevents relapse after total sleep deprivation. Author(s): Department of Neuropsychiatric Sciences, Instituto Scientifico Ospedale San Raffaele, University of Milan, School of Medicine, Milano, Italy. [email protected] Source: Benedetti, F Colombo, C Barbini, B Campori, E Smeraldi, E J-ClinPsychopharmacol. 1999 June; 19(3): 240-5 0271-0749

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Sleep deprivation and its effect on an index of cardiac parasympathetic activity in early nonREM sleep in normal and epileptic subjects. Author(s): Department of Clinical Neurophysiology, King's College Hospital, London. Source: Delamont, R S Julu, P O Jamal, G A Sleepage 1998 August 1; 21(5): 493-8 01618105

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Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals. Author(s): Center for the Study of Biological Rhythms, Universite Libre de Bruxelles, Erasme Campus, 1070, Brussels, Belgium. [email protected] Source: Challet, E Turek, F W Laute, M Van Reeth, O Brain-Res. 2001 August 3; 909(1-2): 81-91 0006-8993

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Sleep deprivation in the rat: an animal model of mania. Author(s): Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy. Source: Gessa, G L Pani, L Fadda, P Fratta, W Eur-Neuropsychopharmacol. 1995; 5 Suppl89-93 0924-977X

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Sleep deprivation reduces LH secretion in men independently of melatonin. Author(s): Department of Psychiatry, University of New Mexico, School of Medicine, Albuquerque. Source: Strassman, R J Qualls, C R Lisansky, E J Peake, G T Acta-Endocrinol-(Copenh). 1991 June; 124(6): 646-51 0001-5598

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Sleep deprivation-induced dermatitis: further support of nicotinic acid depletion in sleep deprivation. Author(s): Tulane University School of Medicine, Department of Pathology, New Orleans, LA 70112. Source: Reimund, E Med-Hypotheses. 1991 December; 36(4): 371-3 0306-9877

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Sleep latency measures of caffeine effects during sleep deprivation. Author(s): Naval Health Research Center, San Diego, CA 92186-5122, USA. [email protected] Source: Kelly, T L Mitler, M M Bonnet, M H Electroencephalogr-Clin-Neurophysiol. 1997 May; 102(5): 397-400 0013-4694

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Sleep phase advance and lithium to sustain the antidepressant effect of total sleep deprivation in bipolar depression: new findings supporting the internal coincidence model? Author(s): Universita Vita-Salute San Raffaele, School of Medicine, Department of Neuropsychiatric Sciences, Via Stamira d'Ancona 20 20127, Milano, Italy. [email protected] Source: Benedetti, F Barbini, B Campori, E Fulgosi, M C Pontiggia, A Colombo, C JPsychiatr-Res. 2001 Nov-December; 35(6): 323-9 0022-3956

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Slow-release caffeine as a countermeasure to driver sleepiness induced by partial sleep deprivation. Author(s): Department of Cognitive and Physiological Psychology, Free University of Brussels, Brussels, Belgium. Source: De Valck, E Cluydts, R J-Sleep-Res. 2001 September; 10(3): 203-9 0962-1105

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Some measures to reduce effects of prolonged sleep deprivation. Author(s): Institut de medecine aerospatiale du service de sante des armees, departement sciences cognitives et ergonomie, Bretigny-sur-Orge, France. Source: Lagarde, D Batejat, D Neurophysiol-Clin. 1995; 25(6): 376-85 0987-7053

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Suppressive effects of enkephalins and REM sleep deprivation on seizures. Author(s): Department of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands. Source: Dzoljic, M R Ukponmwan, O E Baas, A A van den Berg, D J Rupreht, J Dzoljic, M M Epilepsy-Res-Suppl. 1991; 2275-80 0922-9833

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The effects of paradoxical sleep deprivation and valine on spatial learning and brain 5-HT metabolism. Author(s): Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Source: Youngblood, B D Smagin, G N Elkins, P D Ryan, D H Harris, R B PhysiolBehavolume 1999 November; 67(5): 643-9 0031-9384

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

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE DEPRIVATION

MEDICINE

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SLEEP

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to sleep deprivation. 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 sleep deprivation 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 “sleep deprivation” (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 sleep deprivation: •

“Sleep is not tangible” or what the Hebrew tradition has to say about sleep. Author(s): Ancoli-Israel S. Source: Psychosomatic Medicine. 2001 September-October; 63(5): 778-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573026&dopt=Abstract

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Administration of auditory stimulation during recovery after REM sleep deprivation. Author(s): Salin-Pascual RJ, Jimenez-Anguiano A, Duran-Vazquez A, Nancy HM, Drucker-Colin R. Source: Sleep. 1994 April; 17(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7939122&dopt=Abstract

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Auditory arousal thresholds after selective slow-wave sleep deprivation. Author(s): Ferrara M, De Gennaro L, Casagrande M, Bertini M.

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Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 December; 110(12): 2148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616120&dopt=Abstract •

Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow? Author(s): Volk SA, Kaendler SH, Hertel A, Maul FD, Manoocheri R, Weber R, Georgi K, Pflug B, Hor G. Source: Psychiatry Research. 1997 September 29; 75(2): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9351489&dopt=Abstract

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Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Pollock B, Derbyshire S, Nofzinger E, Dew MA, Houck PR, Milko D, Meltzer CC, Kupfer DJ. Source: The American Journal of Psychiatry. 1999 May; 156(5): 683-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327899&dopt=Abstract

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Clinical neurochemical implications of sleep deprivation's effects on the anterior cingulate of depressed responders. Author(s): Wu JC, Buchsbaum M, Bunney WE Jr. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 November; 25(5 Suppl): S74-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682278&dopt=Abstract

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Dissociated paradoxical sleep deprivation effects on inhibitory avoidance and conditioned fear. Author(s): Bueno OF, Lobo LL, Oliveira MG, Gugliano EB, Pomarico AC, Tufik S. Source: Physiology & Behavior. 1994 October; 56(4): 775-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7800747&dopt=Abstract

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Effect of sleep deprivation on brain metabolism of depressed patients. Author(s): Wu JC, Gillin JC, Buchsbaum MS, Hershey T, Johnson JC, Bunney WE Jr. Source: The American Journal of Psychiatry. 1992 April; 149(4): 538-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1554042&dopt=Abstract

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Effect of sleep-wake reversal and sleep deprivation on the circadian rhythm of oxygen toxicity seizure susceptibility. Author(s): Dexter JD, Hof DG, Mengel CE. Source: Aerosp Med. 1972 October; 43(10): 1075-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5076606&dopt=Abstract

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Effects of 24-hour sleep deprivation on rate of decrement in a 10-minute auditory reaction time task. Author(s): Lisper HO, Kjellberg A. Source: J Exp Psychol. 1972 December; 96(2): 287-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4645958&dopt=Abstract

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Effects of adaptogens on granulocytopoiesis during paradoxical sleep deprivation. Author(s): Provalova NV, Skurikhin EG, Suslov NI, Dygai AM, Gol'dberg ED. Source: Bulletin of Experimental Biology and Medicine. 2002 March; 133(3): 261-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360347&dopt=Abstract

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Effects of sleep deprivation on awakening thresholds and sensory evoked potentials in the rat. Author(s): Frederickson CJ, Rechtschaffen A. Source: Sleep. 1978 September; 1(1): 69-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=756058&dopt=Abstract

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Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: a study with Tc-99m-HMPAO SPECT. Author(s): Ebert D, Feistel H, Barocka A. Source: Psychiatry Research. 1991 December; 40(4): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1811242&dopt=Abstract

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Effects of sleep deprivation, lunch, and personality on performance, mood, and cardiovascular function. Author(s): Smith A, Maben A. Source: Physiology & Behavior. 1993 November; 54(5): 967-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8248391&dopt=Abstract

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Electroencephalographic and autonomic activity during and after prolonged sleep deprivation. Author(s): Johnson LC, Slye ES, Dement W. Source: Psychosomatic Medicine. 1965 September-October; 27(5): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5837316&dopt=Abstract

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Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography. Author(s): Volk S, Kaendler SH, Weber R, Georgi K, Maul F, Hertel A, Pflug B, Hor G. Source: Acta Psychiatrica Scandinavica. 1992 December; 86(6): 478-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1471542&dopt=Abstract

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Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment

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outcome in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Houck PR, Dew MA, Ma Y, Mulsant BH, Pollock BG. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2002 September-October; 10(5): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213690&dopt=Abstract •

Increased limbic blood flow and total sleep deprivation in major depression with melancholia. Author(s): Ebert D, Feistel H, Barocka A, Kaschka W. Source: Psychiatry Research. 1994 June; 55(2): 101-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711798&dopt=Abstract

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Influence of sleep deprivation and auditory intensity on reaction time and response force. Author(s): Wlodarczyk D, Jaskowski P, Nowik A. Source: Percept Mot Skills. 2002 June; 94(3 Pt 2): 1101-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186231&dopt=Abstract

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Is pre-attentive processing compromised by prolonged wakefulness? Effects of total sleep deprivation on the mismatch negativity. Author(s): Raz A, Deouell LY, Bentin S. Source: Psychophysiology. 2001 September; 38(5): 787-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577902&dopt=Abstract

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Mechanisms underling the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation. Author(s): Provalova NV, Skurikhin EG, Pershina OV, Suslov NI, Minakova MY, Dygai AM, Gol'dberg ED. Source: Bulletin of Experimental Biology and Medicine. 2002 May; 133(5): 428-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420051&dopt=Abstract

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Neuroendocrinological investigations during sleep deprivation in depression. I. Early morning levels of thyrotropin, TH, cortisol, prolactin, LH, FSH, estradiol, and testosterone. Author(s): Baumgartner A, Graf KJ, Kurten I, Meinhold H, Scholz P. Source: Biological Psychiatry. 1990 October 1; 28(7): 556-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2121292&dopt=Abstract

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Potentiation of metaphit-induced audiogenic seizures by REM sleep deprivation in rats. Author(s): Susic V, Markovic O.

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Source: Physiology & Behavior. 1993 August; 54(2): 331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8372129&dopt=Abstract •

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex. Author(s): Wu J, Buchsbaum MS, Gillin JC, Tang C, Cadwell S, Wiegand M, Najafi A, Klein E, Hazen K, Bunney WE Jr, Fallon JH, Keator D. Source: The American Journal of Psychiatry. 1999 August; 156(8): 1149-58. Erratum In: Am J Psychiatry 1999 October; 156(10): 1666. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10450253&dopt=Abstract

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Psychological effects of Neurotropin in man under normal conditions and after sleep deprivation: a double-blind placebo study. Author(s): Genon JC, Thiebauld C, Lintermans J, De Heyn G. Source: Agressologie. 1989 February; 30(2): 97-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2735497&dopt=Abstract

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Quantitative analysis of the effects of slow wave sleep deprivation during the first 3 h of sleep on subsequent EEG power density. Author(s): Dijk DJ, Beersma DG, Daan S, Bloem GM, Van den Hoofdakker RH. Source: Eur Arch Psychiatry Neurol Sci. 1987; 236(6): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3678290&dopt=Abstract

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Relation between responses to repetitive transcranial magnetic stimulation and partial sleep deprivation in major depression. Author(s): Padberg F, Schule C, Zwanzger P, Baghai T, Ella R, Mikhaiel P, Hampel H, Moller HJ, Rupprecht R. Source: Journal of Psychiatric Research. 2002 May-June; 36(3): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886690&dopt=Abstract

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REM sleep deprivation impairs latent extinction in rats. Author(s): Pearlman C. Source: Physiology & Behavior. 1973 August; 11(2): 233-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4354017&dopt=Abstract

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REM sleep deprivation reduces auditory evoked inhibition of dorsolateral pontine neurons. Author(s): Mallick BN, Fahringer HM, Wu MF, Siegel JM. Source: Brain Research. 1991 June 28; 552(2): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1913194&dopt=Abstract

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RO 15-1788 decreases hypnotic effects of sleep deprivation. Author(s): Lavie P.

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Source: Life Sciences. 1987 July 13; 41(2): 227-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3110524&dopt=Abstract •

Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation--preliminary results. Author(s): Ebert D, Feistel H, Kaschka W, Barocka A, Pirner A. Source: Biological Psychiatry. 1994 June 1; 35(11): 880-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8054411&dopt=Abstract

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Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging. Author(s): Gillin JC, Buchsbaum M, Wu J, Clark C, Bunney W Jr. Source: Depression and Anxiety. 2001; 14(1): 37-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568981&dopt=Abstract

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Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation. Author(s): Eichhammer P, Kharraz A, Wiegand R, Langguth B, Frick U, Aigner JM, Hajak G. Source: Life Sciences. 2002 March 1; 70(15): 1741-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002519&dopt=Abstract

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Sleep deprivation in the rat: XV. Ambient temperature choice in paradoxical sleepdeprived rats. Author(s): Landis CA, Bergmann BM, Ismail MM, Rechtschaffen A. Source: Sleep. 1992 February; 15(1): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1557590&dopt=Abstract

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Sleep deprivation therapy. Author(s): Kuhs H, Tolle R. Source: Biological Psychiatry. 1991 June 1; 29(11): 1129-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1873374&dopt=Abstract

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Sleep deprivation, EEG, and functional MRI in depression: preliminary results. Author(s): Clark CP, Frank LR, Brown GG. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 November; 25(5 Suppl): S79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682279&dopt=Abstract

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Sleep deprivation: a cause of psychotic disorganization. Author(s): Gove WR.

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Source: Ajs; American Journal of Sociology. 1970 March; 75(5): 782-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5535911&dopt=Abstract •

Sleep stage physiology, mood, and vigilance responses to total sleep deprivation in healthy 80-year-olds and 20-year-olds. Author(s): Brendel DH, Reynolds CF 3rd, Jennings JR, Hoch CC, Monk TH, Berman SR, Hall FT, Buysse DJ, Kupfer DJ. Source: Psychophysiology. 1990 November; 27(6): 677-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2100353&dopt=Abstract

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The effect of sleep deprivation on signal detection parameters. Author(s): Deaton M, Tobias JS, Wilkinson RT. Source: Q J Exp Psychol. 1971 November; 23(4): 449-52. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5148928&dopt=Abstract

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The neurophysiological accompaniments of sensory and sleep deprivation and their role in the production of psychological disturbances. Author(s): BRIDGER WH. Source: Recent Adv Biol Psychiatry. 1963; 84: 105-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14282714&dopt=Abstract

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Toward optimal health: the experts respond to sleep deprivation. Interview by Jodi Godfrey Meisler. Author(s): Lee KA, Zammit G. Source: Journal of Women's Health / the Official Publication of the Society for the Advancement of Women's Health Research. 1998 December; 7(10): 1205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9929852&dopt=Abstract

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Urine creatinine excretion: variability and volume dependency during sleep deprivation. Author(s): Rubin RT. Source: Psychosomatic Medicine. 1971 November-December; 33(6): 539-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5148983&dopt=Abstract

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Zolpidem and sleep deprivation: different effect on EEG power spectra. Author(s): Landolt HP, Finelli LA, Roth C, Buck A, Achermann P, Borbely AA. Source: Journal of Sleep Research. 2000 June; 9(2): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10849244&dopt=Abstract

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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/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to sleep deprivation; 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 Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com

•

Herbs and Supplements Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Tyrosine Source: Prima Communications, Inc.www.personalhealthzone.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

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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 SLEEP DEPRIVATION Overview In this chapter, we will give you a bibliography on recent dissertations relating to sleep deprivation. 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 “sleep deprivation” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on sleep deprivation, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Sleep Deprivation 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 sleep deprivation. 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: •

Differential Effects on the Two Cerebral Hemispheres That Result from Loss of REM Sleep Deprivation and Epileptic vs. Nonepileptic Subjects by Dushenko, Terrance William; PhD from The University of Manitoba (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NL06500

•

Sleep Deprivation in the Treatment of Depressive Illness Outcome of Controlled Single Case Studies by Southmayd, Stephen Eric; PhD from Queen's University at Kingston (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK59078

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The Aftereffects of One Night's Sleep Deprivation on Selected Physiological and Psychomotor Parameters by Whittle, Andrew Heath, Jr., PhD from The Florida State University, 1971, 87 pages http://wwwlib.umi.com/dissertations/fullcit/7209220

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•

The Effects of Limited Sleep Deprivation on the Performance of Selected Motor Tasks by Holland, George Joseph, PhD from University of Southern California, 1966, 98 pages http://wwwlib.umi.com/dissertations/fullcit/6608790

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The Effects of Short-Term Cumulative Partial Sleep Deprivation and Recovery Oversleeping on Performance Efficiency, Cognitive Processing, and Subjective Feeling States by Herscovitch, Joel A; PhD from University of Ottawa (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK53234

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The Effects of Sleep Deprivation on Aerobic and Anaerobic Performance by Lindsey, Lewis Robinson, Jr., PhD from The University of Southern Mississippi, 1994, 167 pages http://wwwlib.umi.com/dissertations/fullcit/9430194

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The Effects of Sleep Deprivation on Dynamic Strength and Stamina by Stauffer, Robert Wayne, EDD from Temple University, 1971, 71 pages http://wwwlib.umi.com/dissertations/fullcit/7220224

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 SLEEP DEPRIVATION Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning sleep deprivation.

Recent Trials on Sleep Deprivation The following is a list of recent trials dedicated to sleep deprivation.5 Further information on a trial is available at the Web site indicated. •

Activating Effects of Sleep Deprivation on Synchronized MEG-EEG Recordings of Epilepsy Patients with Non-Diagnostic EEG Condition(s): Epilepsy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will evaluate how the state of being completely deprived of sleep has an effect on recordings of magnetoencephalography (MEG) and electroencephalography (EEG), in relation to how alert someone is and how sleepy someone perceives himself or herself to be. EEG measures electronic potential differences on the scalp. On the other hand, MEG is a non-invasive technique for recording the activity of neurons in the brain, through recording of magnetic fields caused by synchronized neural currents. It has the ability to detect seizures. Because magnetic signals of the brain vary, this technique must balance two key problems: weakness of the signal and strength of the noise. The EEG is sensitive to extra-cellular volume currents, whereas the MEG primarily registers intra-cellular currents. Because electrical fields are quite dependent on the conductive properties of the tissues, and magnetic fields are significantly less distorted by tissue, the MEG has better spatial resolution. There is a great deal of evidence that EEG and MEG provide complementary data about underlying currents of ions. The complex relationship of sleep and epilepsy is well known. Sleep has been used for many years as a powerful EEG activator. Many researchers have supported the hypothesis that there is a specific activating effect of

5

These are listed at www.ClinicalTrials.gov.

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sleep deprivation on epileptic discharges. Sleep deprivation is defined as a sleepless state of longer than 24 hours. The increased use of MEG in diagnosis could improve the procedure for evaluating patients before surgery for epilepsy, by making invasive studies less necessary. Patients 18 years of age or older, with a diagnosis of epilepsy and with a documented last routine EEG (at least 2 weeks earlier) and routine EEG on the day of a baseline MEG-EEG without interictal epileptiform discharges (IEDs) may be eligible for this study. Participants will be rated according to the Epworth, Stanford, and Karolinska Sleepiness Scales, to determine their subjective sleepiness. They will be randomly assigned to stay awake all night or sleep in the hospital overnight. That is, a sleep deprivation and non-sleep deprivation synchronized MEG-EEG recording will be performed in random order. Then the sequence of sleep deprivation and non-sleep deprivation will be reversed within 14 to 21 days. During the recordings, the patient will either sit or lie with his or her head in a helmet covering the entire head, with openings for the eyes and ears. Brain magnetic fields will be recorded with a 275-channel OMEGA system. Throughout the session, visual and two-way audio communication will be maintained with the patient. Recording sessions will last 90 to 180 minutes, with the patient allowed to take breaks after at least 10 minutes in a scanner. Attempts will be made to encourage patients to stay awake and sleep for about the same amount of time during each recording, to acquire comparable amounts of sleep and awake recordings. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071370 •

Combined Behavioral/Pharmacological Therapy for Insomnia Condition(s): Sleep Initiation and Maintenance Disorders; Sleep Deprivation Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine how sleeping pills can be combined with nondrug treatments to maximize the benefits of therapy for insomnia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044629

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 “sleep deprivation” (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 SLEEP DEPRIVATION 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.6 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 “sleep deprivation” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on sleep deprivation, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Sleep Deprivation By performing a patent search focusing on sleep deprivation, 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. 6Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on sleep deprivation: •

Method for predicting alertness and bio-compatibility of work schedule of an individual Inventor(s): Mitchell; Ross E. (4 Allston St., West Newton, MA 02165-2554), Moore-Ede; Martin C. (110 Hundreds Rd., Wellesley Farms, MA 02181) Assignee(s): None Reported Patent Number: 5,433,223 Date filed: November 18, 1993 Abstract: A method enables the prediction of the likely alertness level of an individual at a given point in time based upon the analysis of certain biological and other parameters associated with the individual subject including, circadian phase of the biological clock, accumulated acute or chronic sleep deprivation, shift commencement and termination time, time of last sleep, environmental light, etc. Among other advantages, the method facilitates the creation of bio-compatible schedules for shift workers by providing an accurate model of the likely alertness level of the individual on a specific schedule. Excerpt(s): This invention relates to the prediction of the alertness level of an individual and the suitability of work schedules therefor, especially as related to a shift worker. In the modern world, many organizations rely on around-the-clock operations. Airlines, railroads, nuclear power plants, to name just a few, are entities where safety is of great concern and where it is necessary to ensure staffing twenty-four hours a day. With the advent of around-the-clock operations came the need for the development of shift work schedules as a way to address the requirement for staffing at all hours. It soon became apparent, however, that shift work brings with it its own set of problems. Shift workers often complain of inability to obtain adequate sleep during their off-hours, chronic sleep deprivation, reduced alertness, and even falling asleep on the job, as being realities of the around-the-clock workplace. Web site: http://www.delphion.com/details?pn=US05433223__

•

Method for sleep induction Inventor(s): Boger; Dale (La Jolla, CA), Cravatt; Ben (San Diego, CA), Henriksen; Steven J. (Solana Beach, CA), Lerner; Richard A. (La Jolla, CA), Siuzdak; Gary E. (San Diego, CA) Assignee(s): The Scripps Research Institute (la Jolla, Ca) Patent Number: 5,612,380 Date filed: January 5, 1995 Abstract: Sleep may be induced by administration of fatty acid primary amides, including cis-9,10-octadecenoamide. Furthermore, sleep deprivation may be assayed by analyzing cerebrospinal fluid with respect to the presence of fatty acid primary amides, including cis-9,10-octadecenoamide. The presence of cis-9,10-octadecenoamide in cerebrospinal fluid is correlated with comparative sleep deprivation. Excerpt(s): The invention relates to a method for inducing sleep and to an assay for sleep deprivation. More particularly, the invention relates to a method of inducing

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sleep by administration of fatty acid primary amides, including cis-9,10octadecenoamide, and to a method for assaying sleep deprivation by analyzing cerebrospinal fluid with respect to fatty acid primary amides, including cis-9,10octadecenoamide. Sleep is a natural, periodic behavioral state during which the body rests itself and its physiological powers are restored. It is characterized by a loss of reactivity to the environment. During sleep, certain physiological processes of both the body and the brain function differently than they do during alert wakefulness. Normal sleep consists of at least two quite different behavioral states: synchronized sleep, during which the electroencephalogram consists of slow waves of high amplitude, and desynchronized sleep (DS) or activated sleep characterized by rapid eye movements (REM sleep), in which the electroencephalogram pattern is characterized by waves of high frequency and low amplitude. Synchronized sleep is further characterized by slow and regular respiration, by relatively constant heart rate and blood pressure, and by a predominance of delta waves. Synchronized sleep usually consists of four stages, followed by a period of activated sleep. Each cycle lasts between 80 and 120 minutes. In contrast, desynchronized sleep is further characterized by irregular heart rate and respiration, periods of involuntary muscular jerks and movements, and a higher threshold for arousal. Periods of desynchronized sleep last from 5-20 minutes and occur at about 90 minute intervals during a normal night's sleep. Sleep deprivation can arise from any of a variety of sleep disorders and environmental factors. Insomnia is a common sleep disorder in which the individual is unable to initiate or maintain sleep. In the prior art, there is no known pharmacological method for inducing the full sleep cycle and no known method using biological samples for assaying sleep deprivation. Web site: http://www.delphion.com/details?pn=US05612380__

Patent Applications on Sleep Deprivation As of December 2000, U.S. patent applications are open to public viewing.7 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 sleep deprivation: •

Canine authentic intrauterine sound device Inventor(s): Coats, Genelle; (Pleasanton, CA) Correspondence: Genelle Coats; 774 Neal Place; Pleasanton; CA; 94566; US Patent Application Number: 20030055312 Date filed: September 17, 2001 Abstract: The Canine Authentic Intrauterine Sound Device (CAISD) provides a single, compact, easy to use device for dog owners. The CAISD will provide original, familiar, authentic canine intrauterine sounds to relieve the stress of separation for the new puppy and/or the stress of a canine that has experienced some kind of trauma. The CAISD, equipped with motion and sound sensitivity, will minimize sleep deprivation for both puppy and owner alike, thereby allowing the young new canine the opportunity to adapt to its new environment in as natural a manner as possible.

7

This has been a common practice outside the United States prior to December 2000.

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Excerpt(s): This invention relates to the use of canine authentic intrauterine sounds as a stress reducer for new puppies. This original and novel canine authentic intrauterine sound device would replace the most widely suggested possible resolution to a howling/crying new puppy, the ticking clock and hot water bottle. The idea for a Canine Authentic Intrauterine Sound Device came to me while at my niece's baby shower. I overheard the young women in attendance discussing the use of sounds from the mother's womb that would calm a baby during sleeptime. I thought surely this could work for puppies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treating effects of sleep deprivation and jet lag with NADPH and NADPH Inventor(s): Birkmayer, Joerg G. D.; (Vienna, AT) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030021772 Date filed: June 29, 2001 Abstract: A method for alleviating the symptoms of sleep deprivation or jet lag wherein the reduced form of nicotinamide adenine dinucleotide (NADH) or the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) or physiologically compatible salts or derivatives of NADH and/or NADPH are administered to a human being suffering from the effects. Human beings so treated exhibit an abatement of these effects, such as, for example, decreased attentiveness, decreased ability to concentrate, decreased reaction time, decreased alertness, and decreased productivity and efficiency. Excerpt(s): The present invention relates to a pharmaceutical and a method for treating the effects of sleep deprivation generally, and jet lag specifically. More particularly, the present invention relates to the use of reduced forms of nicotinamide-adeninedinucleotide (NADH) or nicotinamide-adenine-dinucleotide phosphate (NADPH), or physiologically acceptable salts or derivatives thereof, in treating the adverse effects of sleep deprivation and jet lag. Every human being needs a certain amount of sleep each day in order to lead a healthy, productive life. Sleep deprivation is the condition of being deprived of this needed sleep, resulting in adverse effects on an individual, such as, for example, decreased attentiveness, decreased ability to concentrate, decreased reaction time, decreased alertness, and decreased productivity and efficiency. Sleep deprivation can be caused by, for example, sleep disorders, such as insomnia or obstructive sleep apnea, medical illnesses, shifting work schedules, depression, or flying across time zones. Jet lag is a constellation of symptoms that occur in a human being after flying across time zones. It affects a large number of travelers and aircrew. These symptoms include: general malaise, disruption of or deprivation of sleep, gastrointestinal distress, and memory loss. In M. R. Rosekind et al., Fatigue in Operational Settings: Examples from the Aviation Environment, Hum. Factors (1994), 36(2):327-38, the authors estimate that jet lag can degrade decision-making abilities, communication and memory by 30% to 70%. The disruption of the body's entrainment of internal 24-hour cycles of temperature, sleep initiation and other activities to the daylight cycle is believed to be the trigger for jet lag. See G. Copinschi et al., Pathophysiology of Human Circadian Rhythms, Novartis Found. Symp. 2000, 227:14357; F. W. Turek et al., Entrainment of the circadian activity rhythm to the light-dark cycle can be altered by a short-acting benzodiazepine, triazolam, J. Biol. Rhythms (1987), 2(4):249-260. Today's modern jet traveler (soldier, businessperson, athlete, or tourist)

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often is required to perform at a high functional level upon reaching their destination. Furthermore, the problems of jet lag have been compounded in recent years because business travelers are taking more international trips and staying fewer days at their destination. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System and method for evaluating task effectiveness based on sleep pattern Inventor(s): Hursh, Steven Rawlings; (Joppa, MD) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030013943 Date filed: July 6, 2001 Abstract: A method for evaluating the effectiveness of a person to perform a task based on his/her previous or predicted sleep activity is provided. The method can be used to predict changes in task effectiveness at any time of day, based upon numerous patterns of sleep and activity, either experienced or planned for the future. The method take into account progressive increases in sleep deprivation, the effects of the time of day on performance, and changes in the time when a person sleeps and works. The method also accounts for the quality of a sleep interval and a person's sleep inertia, the temporary slowing of performance immediately after awakening. The method is homeostatic. Gradual decreases in sleep debt decrease sleep intensity. Progressive increases in sleep debt produced by extended periods of less than optimal levels of sleep lead to increased sleep intensity. As a result the method can predict the normal decline in sleep intensity during the sleep period and the normal equilibrium of performance under less than optimal schedules of sleep. Excerpt(s): The present invention relates to a system and method for evaluating the effectiveness of a person to perform a task based on his/her preceding or predicted sleep pattern. More particularly, the present invention relates to a system and method for evaluating task effectiveness based on preceding or predicted sleep pattern using calculations that take into account circadian oscillators, a sleep reservoir, sleep intensity, performance use, sleep debt, interruptions to sleep, sleep inertia, and the demands of the task to be performed. Numerous studies have been conducted relating to the analysis of sleep, alertness, and performance. One study is by Jewett and Kronauer, entitled "Interactive Mathematical Models of Subjective Alertness and Cognitive Throughput in Humans," J. Biological Rhythms, 1999; 14(6): pages 588-597. The Jewett and Kronauer model (JK model hereafter) uses arbitrary units and then scales the result from 1 to 0 to fit the actual data, scaled from maximum to minimum. Consequently, the JK model does not make an independent prediction of performance without knowing the range of the results. The JK model makes no provision for predicting the detrimental effects of sleep fragmentation and multiple interruptions in sleep. The JK model uses an oscillator with a large number of arbitrary parameters (van der Pol oscillator) to predict the asymmetrical cycle of performance around the clock. The JK model cannot adjust the phase of the circadian rhythm to reflect shift-work or transmeridian travel without detailed information about ambient light levels. Furthermore, the JK model cannot predict variations in any relevant aspect of operator performance that is of interest to the user. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with sleep deprivation, 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 “sleep deprivation” (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 sleep deprivation. You can also use this procedure to view pending patent applications concerning sleep deprivation. 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 SLEEP DEPRIVATION Overview This chapter provides bibliographic book references relating to sleep deprivation. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on sleep deprivation 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 “sleep deprivation” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “sleep deprivation” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “sleep deprivation” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

21st Century U.S. Army Combat Stress Field Manual (FM 6-22.5) - Sleep Deprivation, Suicide Prevention by Department of Defense; ISBN: 159248302X; http://www.amazon.com/exec/obidos/ASIN/159248302X/icongroupinterna

•

CRIB SHEETS Are You Covered? : New Parent Sleep Deprivation Solutions: Practical and Effective Expectant Parent Strategies by Elizabeth Gardner (Author); ISBN: 0595292852; http://www.amazon.com/exec/obidos/ASIN/0595292852/icongroupinterna

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Epilepsy, Sleep and Sleep Deprivation by Rolf Degen, Ernst Niedermeyer (Editor); ISBN: 0444805214; http://www.amazon.com/exec/obidos/ASIN/0444805214/icongroupinterna

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Epilepsy, Sleep and Sleep Deprivation (Epilepsy Research Supplement, No 2) by Rolf Degan, Ernst Rodin MD (Editor); ISBN: 0444813365; http://www.amazon.com/exec/obidos/ASIN/0444813365/icongroupinterna

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Good Nights: How to Stop Sleep Deprivation, Overcome Insomnia, and Get the Sleep You Need by Gary K. Zammit, et al; ISBN: 0836252756; http://www.amazon.com/exec/obidos/ASIN/0836252756/icongroupinterna

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Sleep Deprivation :.the inner limits of the anxious mind by Daniel Keane (Author); ISBN: 059527174X; http://www.amazon.com/exec/obidos/ASIN/059527174X/icongroupinterna

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Sleep Deprivation Chamber by Adam P. Kennedy, Adrienne Kennedy; ISBN: 0822218127; http://www.amazon.com/exec/obidos/ASIN/0822218127/icongroupinterna

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Sleep Deprivation Chamber: A Theatre Piece by Adam P. Kennedy, Adrienne Kennedy (Contributor); ISBN: 1559361263; http://www.amazon.com/exec/obidos/ASIN/1559361263/icongroupinterna

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Sleep deprivation countermeasures for motorist safety by Jane C. Stutts; ISBN: 0309068681; http://www.amazon.com/exec/obidos/ASIN/0309068681/icongroupinterna

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Sleep Deprivation: Lack of Sleep Can Make You Moody, Ineffective, Even Dangerous [DOWNLOAD: PDF]; ISBN: B00005UF17; http://www.amazon.com/exec/obidos/ASIN/B00005UF17/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 “sleep deprivation” (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:8 •

Alpha depression and lowered pulse rate during delayed actions in a serial reaction test, a study in sleep deprivation. [Tr. from the Swedish]. Author: Bjerner, Bo.; Year: 1996; Stockholm, 1949

•

Effects of rapid eye movement sleep deprivation on the feeding behavior in the laboratory rat: with a description of the cuff pedestal technique Author: Elomaa, Eero.; Year: 1998; Helsinki: Published for the Scandinavian Physiological Society by Blackwell Scientific Publications, 1985

8

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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Sleep deprivation: changes in performance and physiological indicants of activation, by Robert B. Malmo and Walter W. Surwillo. Author: Malmo, Robert B.; Year: 1997; [Washington] American Psychological Assn., 1960

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Sleep disorders sourcebook: basic consumer health information about sleep and its disorders including insomnia, sleepwalking, sleep apnea, restless leg syndrome, and narcolepsy; along with data about shiftwork and its effects, information on the societal costs of sleep deprivation, descriptions of treatment options, a glossary of terms, and resource listings for additional help Author: Swanson, Jenifer.; Year: 1998; Detroit, MI: Omnigraphics, c1999; ISBN: 0780802349 http://www.amazon.com/exec/obidos/ASIN/0780802349/icongroupinterna

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The operational consequences of sleep deprivation and sleep deficit Author: Johnson, Laverne C.; Year: 1991; [London]: North Atlantic Treaty Organization, Advisory Group for Aerospace Research and Development, 1974

Chapters on Sleep Deprivation In order to find chapters that specifically relate to sleep deprivation, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and sleep deprivation 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 “sleep deprivation” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on sleep deprivation: •

Support for the Interstitial Cystitis Patient Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 193-200. Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on support for the IC patient is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. This chapter is written by Vicki Ratner, M.D., the founder and president of the Interstitial Cystitis Association (ICA). The author briefly reviews the history of IC, noting that patients often went years before diagnosis and were forced into a situation of educating themselves and their physicians about the disease. The author then summarizes the history of the ICA and its present role as a support network for patients. The author emphasizes the need for support in dealing with a chronic disease that can disrupt every aspect of one's life. Severe pain, sleep deprivation, and frequent trips to the bathroom can make it difficult to maintain relationships, hold a job, or participate in social activities. Support services can make a critical difference in coping with IC. The chapter concludes with the contact information for the ICA.

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How Vocal Abilities Can Be Limited by Immune System Reactions to 'Invaders' Source: in Thurman, L. and Welch, G., eds. Bodymind and Voice: Foundations of Voice Education, Volumes 1-3. 2nd ed. Collegeville, MN: VoiceCare Network. 2000. p. 538-545. Contact: Available from National Center for Voice and Speech (NCVS). Book Sales, 334 Speech and Hearing Center, University of Iowa, Iowa City, IA 52242. Website: www.ncvs.org. PRICE: $75.00 plus shipping and handling. ISBN: 0874141230. Summary: This chapter on the immune system is from a multi-volume text that brings a biopsychosocial approach to the study of the voice. The authors use the phrase 'bodyminds' to describe the interrelationship of perception, memory, learning, behavior, and health, as they combine to affect all environmental interactions, adaptations, and learning. The books are written for teachers, voice professionals, people who use their voices on an avocational basis, and interested members of the general public. This chapter describes the function of the immune system and how the vocal abilities can be limited by immune system reactions. Topics include bacterial, viral and fungal infections of the respiratory tract; allergies; and cancer. Inflammation that relates to the voice can occur in response to infective pathogens and their products, allergenic substances and their products, toxic or irritant substances (gasses, acids, particles) that are deposited or released onto the mucosal tissues of the respiratory tract, relatively intense impact and shearing forces during extensive or vigorous voicing, or imbalances in immune endocrine chemistry due to stress or sleep deprivation. When the vocal folds are inflamed (due to any of these reasons) and hoarseness is present, they are more vulnerable to the impact and shearing stresses that come from misuse or overuse. Extensive, vigorous, and inefficient voice use can more easily create serious voice disorders when preexisting tissue inflammation is present. 45 references.

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CHAPTER 8. MULTIMEDIA ON SLEEP DEPRIVATION Overview In this chapter, we show you how to keep current on multimedia sources of information on sleep deprivation. 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 Sleep Deprivation 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 sleep deprivation (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 sleep deprivation: •

The sleep famine [videorecording]: the effects of sleep deprivation and chronic fatigue Source: a presentation of Films for the Humanities and Sciences; produced and distributed by the Canadian Broadcasting Corporation; Year: 2001; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2001

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CHAPTER 9. PERIODICALS DEPRIVATION

AND

NEWS

ON

SLEEP

Overview In this chapter, we suggest a number of news sources and present various periodicals that cover sleep deprivation.

News Services and Press Releases One of the simplest ways of tracking press releases on sleep deprivation 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 “sleep deprivation” (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 sleep deprivation. 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 “sleep deprivation” (or synonyms). The following was recently listed in this archive for sleep deprivation: •

Sleep deprivation common in US children: report Source: Reuters Health eLine Date: October 23, 2002

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Sleep deprivation common in children, may have long-term consequences Source: Reuters Medical News Date: October 23, 2002

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Sleep deprivation may lower immune response to flu vaccination Source: Reuters Medical News Date: September 24, 2002

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Sleep deprivation alters hormonal activity Source: Reuters Medical News Date: June 24, 2002

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Mild sleep deprivation alters hormonal activity Source: Reuters Health eLine Date: June 24, 2002

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US teens suffering weekday sleep deprivation Source: Reuters Health eLine Date: April 18, 2002

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Sleep deprivation does not affect junior doctors' judgment Source: Reuters Medical News Date: January 25, 2002

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Sleep deprivation ups risk of surgical mistakes Source: Reuters Health eLine Date: November 23, 2001

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Sleep deprivation increases risk of depression in family caregivers Source: Reuters Medical News Date: January 01, 2001

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Cognitive, motor impairment similar for sleep deprivation and alcohol intoxication Source: Reuters Medical News Date: September 21, 2000

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Sleep deprivation alters brain activation patterns Source: Reuters Medical News Date: February 10, 2000

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Long commutes linked to sleep deprivation, other disorders Source: Reuters Medical News Date: September 16, 1999

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Interleukin-6 levels rise following sleep deprivation and may regulate sleep Source: Reuters Medical News Date: August 23, 1999

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Sleep deprivation plus antidepressant medication may benefit elderly depressed patients Source: Reuters Medical News Date: June 01, 1999

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Sleep deprivation raises blood pressure Source: Reuters Health eLine Date: February 18, 1999

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Sleep deprivation increases blood pressure in hypertensive patients Source: Reuters Medical News Date: February 18, 1999

Periodicals and News

•

Sleep Deprivation More Serious A Problem Than Appreciated Source: Reuters Medical News Date: March 26, 1998

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Sleep Deprivation Common, Says Survey Source: Reuters Health eLine Date: March 25, 1998

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Sleep Deprivation Lowers Percentage of Natural Killer Cells In Blood Source: Reuters Medical News Date: June 17, 1997

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Sleep Deprivation Affects Immune Cells Source: Reuters Health eLine Date: June 17, 1997

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Sleep Deprivation While Driving Called a Major Public Health Threat Source: Reuters Medical News Date: May 29, 1996

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Severe Sleep Deprivation A Consequence Of ICU Source: Reuters Medical News Date: June 28, 1995

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “sleep deprivation” (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.

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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 “sleep deprivation” (or synonyms). If you know the name of a company that is relevant to sleep deprivation, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “sleep deprivation” (or synonyms).

Academic Periodicals covering Sleep Deprivation Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to sleep deprivation. In addition to these sources, you can search for articles covering sleep deprivation that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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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 Institute9: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

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

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

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/

9

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

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.10 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:11 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

10

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). 11 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “sleep deprivation” (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 4164 65 851 2 16 5098

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “sleep deprivation” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

12

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

13

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). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16

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 Biologists17 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.18 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.19 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/.

17 Adapted 18

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. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on sleep deprivation 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 sleep deprivation. 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 sleep deprivation. 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 “sleep deprivation”:

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Other guides Sleep Apnea http://www.nlm.nih.gov/medlineplus/sleepapnea.html Sleep Disorders http://www.nlm.nih.gov/medlineplus/sleepdisorders.html Sudden Infant Death Syndrome http://www.nlm.nih.gov/medlineplus/suddeninfantdeathsyndrome.html Toilet Training and Bedwetting http://www.nlm.nih.gov/medlineplus/toilettrainingandbedwetting.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on sleep deprivation. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Pediatric Obstructive Sleep Apnea Source: Alexandria, VA: American Academy of Otolaryngology-Head and Neck Surgery. 2003. Contact: Available from American Academy of Otolaryngology-Head and Neck Surgery. One Prince St., Alexandria, VA 22314-3357. (703) 836-4444. TTY: (703) 519-1585. Web site: www.entnet.org/kidsent. PRICE: Available free online. Summary: Sleep disordered breathing (SDB) can lead to a number of health-related problems in children, such as snoring, sleep deprivation, abnormal urine production, slowed growth, and the learning problems attention deficit disorder and attention deficit hyperactivity disorder. This fact sheet provides background information on pediatric obstructive sleep apnea, including its consequences, diagnosis, and treatment.

•

Fibromyalgia Source: Detroit, MI: American Autoimmune Related Diseases Association, Inc. 1997. 4 p. Contact: Available from American Autoimmune Related Diseases Association, Inc. (AARDA). Michigan National Bank Building, 15475 Gratiot Avenue, Detroit, MI 48205. (313) 371-8600. Website: www.aarda.org. PRICE: Single copy free; send self-addressed, stamped envelope.

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Summary: This fact sheet for people with fibromyalgia discusses the affected population, symptoms, diagnosis, and treatment of this common disorder. Three to six million Americans may have the symptoms of fibromyalgia, such as widespread pain and tenderness, particularly around the affected joints and muscles. Fibromyalgia pain is influenced by many intrinsic factors and tends to fluctuate, but it is never completely relieved. It is usually most severe in the morning and late evening, and it is accompanied by diffuse stiffness. Other complaints include swollen joints, fatigue, sleep deprivation, anxiety, tension headaches, neurologic symptoms, irritable bowel syndrome, and dry eyes and mouth. Diagnosis is based on finding tender points in the presence of widespread pain, but other inflammatory conditions that present with similar symptoms must be ruled out. Various treatment approaches have been tried, including eliminating contributing factors, using nonsteroidal anti-inflammatory drugs, exercising, and providing the body with adequate nourishment. The fact sheet also explains what autoimmunity is and outlines the activities of the American Autoimmune Related Diseases Association. •

Sleep and Tinnitus Source: London, England: Royal National Institute for Deaf People. 199x. [4 p.]. Contact: Available from RNID Helpline. P.O. Box 16464, London EC1Y 8TT, United Kingdom. 0870 60 50 123. Fax 0171-296 8199. E-mail: [email protected]. Website: www.rnid.org.uk. Also available from RNID Tinnitus Helpline. Castle Cavendish Works, Norton Street, Radford, Nottingham NG7 5PN, United Kingdom. 0345 090210. Fax 0115-978 5012. E-mail: [email protected]. PRICE: Single copy free. Summary: This fact sheet from the Royal National Institute for Deaf People (RNID) discusses sleep and tinnitus (ringing or other noises in the ears), describes the impact of sleep deprivation, and notes how the symptoms of sleep deprivation are similar to those felt by people who are dealing with tinnitus. The fact sheet discusses the relationship these two conditions. Medical professionals disagree about whether it is tinnitus or the tension, anxiety and depression associated with it that disturb the sleeper. Other topics covered include the use of sedatives or tranquilizers, sleep assessment techniques, relaxation methods to help with sleep, the different types of sleep disturbance, the 'vicious cycle' of sleep deprivation and worry about sleep deprivation, changing sleep patterns with age, and tips for things to try and to avoid in order to maximize sleep habits. One sidebar summarizes six steps to sound sleep. The fact sheet mentions a few books and articles that may offer additional information. 4 references. 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 sleep deprivation. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to sleep deprivation. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with sleep deprivation. 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 sleep deprivation. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “sleep deprivation” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received

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your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “sleep deprivation”. 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 “sleep deprivation” (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 “sleep deprivation” (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.20

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

20

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)21: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

21

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

•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

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

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

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

169

SLEEP DEPRIVATION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-hydroxyindoleacetic acid: 5HIAA. A break-down product of serotonin that is excreted in the urine. Serotonin is a hormone found in high levels in many body tissues. Serotonin and 5HIAA are produced in excess amounts by carcinoid tumors, and levels of these substances may be measured in the urine to test for carcinoid tumors. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

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Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal 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] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] 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] Aged, 80 and Over: A person 80 years of age and older. [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] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and

Dictionary 171

renal disease. [EU] 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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [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] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH]

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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] 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]

Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [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]

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Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apnoea: Cessation of breathing. [EU] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteritis: Inflammation of an artery. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including

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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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [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] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Automobile Driving: The effect of environmental or physiological factors on the driver and driving ability. Included are driving fatigue, and the effect of drugs, disease, and physical disabilities on driving. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] 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] Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [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] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH]

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Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [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] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] 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] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [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] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] 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]

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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] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bladder: The organ that stores urine. [NIH] Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [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 Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] 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

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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]

Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Bruxism: A disorder characterized by grinding and clenching of the teeth. [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] Burning Mouth Syndrome: A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their

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three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] 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] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] 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] 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 reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] 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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell

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adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] 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] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Child Psychology: The study of normal and abnormal behavior of children. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU]

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Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] 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] 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] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical 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] Clomipramine: A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [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] 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] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational

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beliefs with more realistic and functional ones.

[NIH]

Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH]

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Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] 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] 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] Concomitant: Accompanying; accessory; joined with another. [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] Consolidation: The healing process of a bone fracture. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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 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

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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] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross-Cultural Comparison: Comparison of various psychological, sociological, or cultural factors in order to assess the similarities or diversities occurring in two or more different cultures or societies. [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] Cystitis: Inflammation of the urinary bladder. [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] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] 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]

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Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextrocardia: Location of the heart in the right hemithorax, with the apex directed to the right. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] 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] 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]

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Dilatation: The act of dilating. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. [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] Dreams: A series of thoughts, images, or emotions occurring during sleep which are dissociated from the usual stream of consciousness of the waking state. [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] Duct: A tube through which body fluids pass. [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

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disease may be referred to as dyskinesia syndromes (movement disorders). Dyskinesias are also a relatively common manifestation of basal ganglia diseases. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] 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] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emetic: An agent that causes vomiting. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [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]

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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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endometrium: The layer of tissue that lines the uterus. [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] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] 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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH]

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Erythropoiesis: The production of erythrocytes. [EU] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] 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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [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] 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]

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Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] 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] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] 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.

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[NIH]

Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH]

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Geriatric: Pertaining to the treatment of the aged. [EU] 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] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] 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

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the limbic system. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [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] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [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] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [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]

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Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypophyseal: Hypophysial. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral

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walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] 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] 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 Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In 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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] 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]

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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] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which

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regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] 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] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intrinsic Factor: A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12. Deficiency of intrinsic factor results in pernicious anemia. [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]

Investigative Techniques: Investigative techniques used in pre-clinical and clinical research, epidemiology, chemistry, immunology, genetics, etc. They do not include techniques specifically applied to diagnosis; therapeutics; anesthesia and analgesia, surgery, operative, and dentistry. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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

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mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [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] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [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] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or

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spore to the fertilized ovum or spore of the next generation. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] 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] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant,

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and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

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] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Magnetoencephalography: The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides information about the localization of brain activity which is complementary to that provided by electroencephalography. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] 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] Maprotiline: A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use. [NIH]

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Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Eminence: Raised area on the infundibular hypothalamus at the floor of the third ventricle of the brain which contains the primary capillary network of the hypophyseal portal system. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [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

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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] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] 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] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mode of Transmission: Hepatitis A [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] 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

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absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monocular: Diplopia identified with one eye only; it may be induced with a double prism, or it may occur either as a result of double imagery due to an optical defect in the eye, or as a result of simultaneous use of normal and anomalous retinal correspondence. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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]

Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] 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] Mutagenic: Inducing genetic mutation. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] 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] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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,

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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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] 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] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [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] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [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] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxin: A substance that is poisonous to nerve tissue. [NIH]

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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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] 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] Nocturia: Excessive urination at night. [EU] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oestradiol: Growth hormone. [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]

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Opacity: Degree of density (area most dense taken for reading). [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [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]

Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]

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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] 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 Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] 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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [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] Parturition: The act or process of given birth to a child. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

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Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penile Erection: The state of the penis when the erectile tissue becomes filled with blood and causes the penis to become rigid and elevated. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] 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] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] 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] Phentermine: A central nervous system stimulant and sympathomimetic with actions and uses similar to those of dextroamphetamine. It has been used most frequently in the treatment of obesity. [NIH]

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Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] 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] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] 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] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH]

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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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Pontine: A brain region involved in the detection and processing of taste. [NIH] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Postural: Pertaining to posture or position. [EU] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Power Plants: Units that convert some form of energy into electrical energy, such as hydroelectric or steam-generating stations, diesel-electric engines in locomotives, or nuclear power plants. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and

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costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenstrual: Occurring before menstruation. [EU] 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] 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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of

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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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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

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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] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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. [NIH]

Quality of Life: A generic concept reflecting concern with the modification and

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enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Railroads: Permanent roads having a line of rails fixed to ties and laid to gage, usually on a leveled or graded ballasted roadbed and providing a track for freight cars, passenger cars, and other rolling stock. Cars are designed to be drawn by locomotives or sometimes propelled by self-contained motors. (From Webster's 3d) The concept includes the organizational and administrative aspects of railroads as well. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] 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] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recuperation: The recovery of health and strength. [EU] 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]

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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] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

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] Resident physician: A physician who lives in a hospital and is constantly available, as an intern. [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] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] Retrospective: Looking back at events that have already taken place. [NIH]

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Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk-Taking: Undertaking a task involving a challenge for achievement or a desirable goal in which there is a lack of certainty or a fear of failure. It may also include the exhibiting of certain behaviors whose outcomes may present a risk to the individual or to those associated with him or her. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saccades: An abrupt voluntary shift in ocular fixation from one point to another, as occurs in reading. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola

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carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] 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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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

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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] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] 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] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sister Chromatid Exchange: An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in Bloom syndrome. [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

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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 Bruxism: A sleep disorder characterized by grinding and clenching of the teeth and forceful lateral or protrusive jaw movements. Sleep bruxism may be associated with tooth injuries; temporomandibular joint disorders; sleep disturbances; and other conditions. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Snoring: Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] 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] Soporific: 1. Causing or inducing profound sleep. 2. A drug or other agent which induces sleep. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles

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are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] 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] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [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] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [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] 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

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clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH]

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Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [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] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH]

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Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [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] Tooth Injuries: Traumatic or other damage to teeth including fractures (tooth fractures) or displacements (tooth luxation). [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] 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] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is

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analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] 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] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is

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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] 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] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] 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

Dictionary 225

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] Verbal Learning: Learning to respond verbally to a verbal stimulus cue. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [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] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH]

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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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]

227

INDEX 5 5-hydroxyindoleacetic acid, 34, 83, 169 A Abdominal, 169, 196, 206 Abdominal Pain, 169, 196 Aberrant, 100, 169 Acceptor, 169, 205 Acetylcholine, 13, 42, 46, 62, 169, 179, 204 Acoustic, 39, 44, 169, 225 Adaptation, 57, 68, 169, 195, 208 Adenine, 134, 169 Adenosine, 12, 16, 17, 26, 40, 57, 60, 66, 169, 177, 208 Adenosine Kinase, 61, 169 Adipocytes, 169, 197 Adjustment, 169 Adolescence, 8, 32, 169, 207 Adrenal Cortex, 170, 183, 188, 210 Adrenal Medulla, 170, 178, 187, 204 Adrenergic, 79, 170, 171, 185, 187, 220 Adverse Effect, 45, 134, 170, 173, 217 Aerobic, 66, 67, 90, 126, 170, 188 Aerobic Exercise, 90, 170 Afferent, 170, 197, 210, 216 Affinity, 170, 174 Age Groups, 22, 170 Age of Onset, 17, 26, 170, 223 Aged, 80 and Over, 170 Agonist, 17, 40, 50, 77, 79, 170, 173, 177, 185, 194, 197, 202 Airway, 3, 13, 18, 21, 39, 43, 64, 79, 170, 218 Airway Obstruction, 43, 170 Airway Resistance, 3, 170 Albumin, 170, 205 Alertness, 10, 27, 31, 38, 39, 58, 67, 71, 74, 85, 89, 92, 93, 110, 111, 132, 134, 135, 171, 177 Algorithms, 5, 58, 171, 175 Alkaloid, 171, 174, 180, 202, 215 Alleles, 37, 171, 192 Allergen, 171, 216 Alpha-1, 171 Alternative medicine, 145, 171 Alveoli, 171, 224 Ambulatory Care, 171 Amine, 171, 175, 192 Amino Acid Sequence, 171, 172, 175, 188

Amino Acids, 85, 171, 175, 203, 207, 209, 212, 215, 223 Amitriptyline, 68, 100, 171 Ammonia, 171, 191 Amnestic, 171, 189 Amphetamine, 15, 33, 65, 75, 81, 95, 172, 184 Amygdala, 52, 172, 198, 217 Anaerobic, 66, 126, 172 Anaesthesia, 102, 172, 195 Anal, 11, 82, 172, 189, 198 Analgesic, 172, 202, 205 Analog, 33, 51, 172 Analysis of Variance, 52, 53, 172 Anatomical, 42, 49, 172, 194, 203 Anesthesia, 12, 60, 170, 172, 196 Anesthetics, 172, 187 Animal model, 6, 11, 28, 29, 32, 39, 41, 42, 59, 63, 112, 172 Anions, 170, 172, 196 Antagonism, 172, 177 Anthropometry, 44, 172 Antibodies, 172, 193, 194, 199 Antibody, 170, 172, 173, 181, 193, 194, 195, 200, 216 Anticholinergic, 171, 173 Anticonvulsant, 173, 177, 198 Antidiuretic, 5, 173 Antiepileptic, 21, 173 Antigen, 54, 170, 172, 173, 181, 193, 194, 195, 200, 216 Anti-inflammatory, 5, 157, 173 Antispasmodic, 173, 205, 216 Anus, 172, 173, 176, 196, 213 Anxiety, 9, 11, 14, 53, 66, 120, 157, 173, 189, 198, 206, 210, 216 Apnea, 18, 20, 21, 34, 39, 43, 61, 156, 173 Apnoea, 74, 173 Apomorphine, 85, 173 Apoptosis, 47, 173 Aqueous, 173, 175, 183, 186 Arachidonic Acid, 173, 211 Arginine, 173, 204 Arterial, 173, 193, 212, 221 Arteries, 173, 176, 182, 201 Arteritis, 4, 173 Assay, 26, 132, 173 Astringents, 173, 200

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Astrocytes, 173, 201 Asymptomatic, 7, 174 Atrophy, 24, 174 Atropine, 174, 216 Attenuated, 16, 24, 174 Atypical, 4, 174, 204 Auditory, 32, 69, 73, 86, 89, 115, 117, 118, 119, 174, 188, 210, 224 Autoimmune disease, 174 Autoimmunity, 157, 174 Automobile Driving, 51, 174 Autonomic, 7, 45, 48, 55, 57, 97, 117, 169, 174, 204, 207, 218, 220 Autonomic Nervous System, 45, 57, 174, 207, 218, 220 Autoradiography, 13, 174 Autoreceptors, 13, 50, 174 Axillary, 77, 174 Axons, 174, 184, 196, 210 B Bacteria, 173, 174, 186, 187, 201, 217, 222, 224 Bacterial Physiology, 169, 174 Bacterium, 174, 181 Basal Ganglia, 52, 57, 175, 186, 198 Base, 15, 169, 175, 184, 197, 221 Bed Rest, 15, 175 Benign, 175, 178, 192 Benzene, 175 Benzodiazepines, 5, 27, 175 Bereavement, 23, 175 Beta-Endorphin, 75, 175 Bile, 175, 190, 198, 219 Bile Acids, 175, 190, 219 Biochemical, 29, 37, 56, 61, 171, 175, 217 Biogenesis, 23, 175 Biogenic Monoamines, 50, 175 Biomarkers, 44, 45, 175 Biosynthesis, 23, 46, 173, 175, 223 Biotechnology, 65, 138, 145, 151, 175 Biotransformation, 176 Biphasic, 52, 176 Bladder, 4, 5, 139, 176, 183, 194, 211, 224 Blinking, 79, 176 Bloating, 176, 196 Blood Glucose, 52, 176, 195 Blood Platelets, 176, 217 Blood pressure, 7, 39, 43, 44, 105, 133, 144, 176, 178, 193, 201 Blood transfusion, 176, 192 Blood vessel, 176, 178, 179, 187, 197, 198, 207, 218, 219, 221, 224

Blood Viscosity, 176, 192 Blot, 26, 31, 47, 176 Body Fluids, 175, 176, 185, 223 Body Mass Index, 176, 205 Bone Marrow, 175, 176, 194, 202 Bone scan, 176, 215 Bowel, 172, 176, 184, 219 Bowel Movement, 176, 184, 219 Bradykinin, 176, 204 Brain Stem, 13, 177, 179 Branch, 165, 177, 186, 206, 212, 219, 221 Bronchi, 177, 187, 222 Bronchial, 177, 192 Bronchoconstriction, 13, 177 Bronchoscopy, 72, 177 Bronchus, 177 Bruxism, 177, 218 Bulimia, 59, 177 Bupropion, 57, 101, 177 Burning Mouth Syndrome, 4, 177 C Caffeine, 16, 57, 65, 71, 74, 78, 80, 81, 89, 103, 110, 111, 112, 113, 177 Calcium, 177, 181, 217 Capillary, 176, 177, 200, 209 Carbachol, 35, 177 Carbamazepine, 76, 177 Carbohydrate, 4, 178, 191, 209, 216 Carbon Dioxide, 178, 183, 189, 190, 208, 214 Carcinogenic, 175, 178, 195, 211, 219 Carcinogens, 178, 204 Carcinoid, 169, 178 Cardiac, 28, 44, 112, 177, 178, 187, 188, 202, 205, 214, 219 Cardiopulmonary, 178, 192 Cardiopulmonary Bypass, 178, 192 Cardiorespiratory, 170, 178 Cardiovascular, 7, 18, 20, 28, 44, 45, 55, 73, 117, 172, 178, 188, 217, 218 Cardiovascular disease, 7, 28, 44, 178 Case report, 91, 108, 178 Case series, 21, 178 Catecholamine, 15, 33, 178, 185, 207 Cations, 178, 196 Caudal, 178, 184, 193, 209 Causal, 45, 178, 196 Cell Adhesion, 20, 178 Cell Adhesion Molecules, 20, 178 Cell Death, 173, 179, 203 Cell Differentiation, 179, 217

Index

Cell Division, 174, 179, 200, 201, 208, 211, 216 Cell membrane, 16, 179, 184, 190, 208 Cell proliferation, 179, 217 Cell Respiration, 179, 214 Central Nervous System Infections, 179, 192 Cerebellum, 179, 183, 189, 209 Cerebral hemispheres, 175, 177, 179, 221 Cerebrospinal, 26, 36, 83, 132, 133, 179 Cerebrospinal fluid, 26, 36, 83, 132, 133, 179 Cerebrovascular, 178, 179 Cerebrum, 179, 183, 208, 221 Character, 179, 183 Child Psychology, 12, 179 Choline, 46, 62, 179 Cholinergic, 12, 33, 37, 39, 40, 56, 60, 171, 177, 179, 180, 216 Cholinergic Agonists, 39, 180 Chromatin, 173, 180 Chromosome, 180, 198, 216, 217 Chronic Disease, 26, 139, 180 Circadian Rhythm, 13, 14, 21, 28, 30, 31, 57, 59, 72, 75, 99, 104, 112, 116, 134, 135, 180 CIS, 132, 133, 180, 214 Clamp, 61, 180 Clear cell carcinoma, 180, 184 Clinical trial, 6, 36, 65, 127, 129, 151, 180, 182, 212, 213 Clomipramine, 63, 88, 100, 180 Cloning, 175, 180 Coca, 180 Cocaine, 19, 29, 40, 110, 180 Cochlear, 180, 222, 225 Cochlear Diseases, 180, 222 Cofactor, 180, 211 Cognition, 18, 19, 32, 33, 180 Cognitive restructuring, 180, 219 Colitis, 181, 197 Collagen, 54, 181, 189, 209, 211 Collapse, 18, 43, 181, 218 Combination Therapy, 181, 188 Competency, 12, 181 Complement, 181, 216 Complementary and alternative medicine, 115, 122, 181 Complementary medicine, 115, 181 Complete remission, 181, 214 Computational Biology, 151, 182 Computed tomography, 182, 215

229

Computerized axial tomography, 182, 215 Computerized tomography, 101, 117, 120, 182 Concomitant, 33, 182 Conjunctiva, 182, 223 Connective Tissue, 176, 181, 182, 190, 199, 215 Consciousness, 172, 182, 184, 185, 214 Consolidation, 36, 55, 58, 182 Constipation, 182, 196 Consumption, 43, 182, 205 Continuum, 43, 182 Contraindications, ii, 182 Control group, 22, 33, 53, 182, 213 Controlled study, 11, 23, 88, 182 Coordination, 39, 49, 179, 182 Coronary, 178, 182, 183, 201 Coronary heart disease, 178, 182 Coronary Thrombosis, 183, 201 Cortex, 13, 48, 63, 64, 99, 183, 187, 188, 189, 203, 210 Cortical, 13, 23, 32, 36, 42, 48, 51, 64, 74, 75, 183, 188, 210, 216 Cortices, 52, 183 Cortisol, 44, 52, 57, 62, 74, 75, 81, 84, 93, 95, 108, 118, 170, 183 Cranial, 179, 183, 192, 196, 203, 204, 207, 223, 224, 225 Craniocerebral Trauma, 183, 192, 222 Creatinine, 107, 121, 183 Critical Care, 60, 79, 103, 183 Cross-Cultural Comparison, 57, 183 Curative, 183, 204, 221 Cyclic, 104, 177, 183, 191, 204, 211, 216 Cystitis, 4, 139, 183 Cytokine, 9, 61, 183 Cytoplasm, 173, 179, 183, 191, 202, 215 Cytotoxic, 183, 217 D Data Collection, 22, 44, 183 Databases, Bibliographic, 151, 183 Decarboxylation, 175, 183, 192, 202 Degenerative, 26, 35, 183, 202 Deletion, 60, 173, 184, 190 Delusions, 184, 212 Dementia, 98, 184 Dendrites, 184, 203 Density, 35, 47, 98, 119, 176, 184, 205 Dentate Gyrus, 184, 192 Depolarization, 184, 217 Depressive Disorder, 66, 184, 198

230

Sleep Deprivation

Deprivation, 1, 3, 4, 6, 7, 9, 15, 16, 18, 20, 25, 28, 29, 30, 31, 32, 40, 41, 47, 48, 50, 51, 54, 55, 56, 59, 60, 61, 62, 64, 65, 75, 77, 80, 92, 93, 94, 102, 103, 106, 112, 115, 120, 125, 128, 131, 132, 133, 134, 136, 137, 138, 139, 141, 143, 144, 146, 155, 157, 158, 159, 184 Dermatitis, 112, 184 DES, 111, 113, 184 Dextroamphetamine, 98, 172, 184, 201, 207 Dextrocardia, 91, 184 Diagnostic procedure, 131, 145, 184 Diarrhea, 184, 196 Diastolic, 184, 193 Diencephalon, 184, 187, 193, 210, 221 Digestive system, 129, 184 Dilatation, 185, 210 Direct, iii, 17, 23, 37, 62, 64, 72, 77, 185, 207, 209, 214, 220 Discrimination, 24, 185 Disposition, 8, 185 Dissection, 15, 185 Dissociation, 94, 170, 185 Dissociative Disorders, 185 Distal, 185, 190, 210, 212 Diuresis, 177, 185 Diurnal, 9, 13, 31, 74, 77, 97, 185 Dopamine, 16, 27, 37, 56, 69, 77, 78, 81, 85, 101, 120, 172, 173, 177, 180, 184, 185, 201, 208 Dopamine Agents, 27, 185 Dorsal, 35, 49, 52, 185, 187, 209, 217 Dorsum, 185 Dreams, 47, 185 Drive, ii, vi, 5, 10, 38, 39, 51, 57, 109, 185 Drug Interactions, 185 Duct, 185, 215 Dyskinesias, 185, 202 Dyspareunia, 186, 188 Dysphoric, 73, 75, 104, 184, 186 E Effector, 169, 181, 186, 204 Effector cell, 186, 204 Efficacy, 11, 31, 35, 45, 110, 186, 198, 223 Ejaculation, 110, 186, 216 Elastin, 181, 186 Elective, 101, 186 Electroencephalography, 82, 83, 99, 103, 127, 186, 199 Electrons, 175, 186, 196, 199, 205, 213 Electrophysiological, 42, 56, 186 Elementary Particles, 186, 199, 212

Embolus, 186, 195 Embryo, 179, 186, 195 Emetic, 173, 186 Empirical, 32, 51, 186 Emulsion, 174, 186, 189 Endocrine System, 187, 203 Endocrinology, 5, 187 Endometrium, 187, 200 Endothelium, 187, 204 Endothelium-derived, 187, 204 Endotoxin, 187, 223 End-stage renal, 4, 187 Energy balance, 187, 197 Enkephalin, 175, 187 Entorhinal Cortex, 187, 192 Environmental Exposure, 6, 187, 204 Environmental Health, 150, 152, 187 Enzymatic, 175, 177, 181, 187, 192, 214 Enzyme, 23, 46, 50, 61, 62, 86, 169, 186, 187, 191, 201, 217, 223, 225 Epidemic, 28, 187 Epidemiological, 52, 187 Epinephrine, 52, 170, 185, 187, 204, 224 Epithalamus, 184, 187, 198 Erectile, 187, 207 Erythrocytes, 176, 187, 188, 216 Erythropoiesis, 111, 118, 188 Esophagus, 184, 188, 190, 199, 207, 219 Estradiol, 22, 42, 93, 118, 188 Estrogen, 22, 188, 211 Estrogen Replacement Therapy, 22, 188 Evoke, 188, 219 Evoked Potentials, 73, 107, 117, 188 Excitability, 13, 42, 47, 74, 75, 188, 203 Excitatory, 188, 191, 194, 197 Excitatory Amino Acid Agonists, 188, 197 Exercise Test, 188 Exercise Tolerance, 110, 188 Exogenous, 22, 31, 32, 60, 176, 188, 223 Exon, 60, 188 Expiration, 188, 214 Extracellular, 47, 60, 61, 174, 182, 188, 189, 201 Extracellular Space, 188, 201 Extrapyramidal, 185, 188 Extremity, 16, 189 Eye Movements, 133, 189 F Failure to Thrive, 8, 189 Family Planning, 151, 189 Fat, 34, 111, 169, 173, 176, 183, 186, 189, 197, 198, 205, 215

Index

Fathers, 53, 189 Fatigue, 5, 11, 28, 40, 53, 58, 61, 65, 88, 134, 141, 157, 174, 189 Fatty acids, 28, 170, 189, 211 Feeding Behavior, 138, 189 Fentanyl, 70, 189 Fibroblasts, 189, 196 Fissure, 184, 189, 210 Fixation, 189, 215, 216 Fluoxetine, 102, 189 Fluvoxamine, 100, 189 Forearm, 176, 189 Fourth Ventricle, 189, 198, 221 Friction, 170, 190 Frontal Lobe, 117, 190, 210 Functional magnetic resonance imaging, 51, 64, 190 G Gallbladder, 169, 184, 190 Ganglia, 169, 190, 203, 207, 220 Gap Junctions, 190, 220 Gas, 171, 178, 190, 193, 196, 204, 214, 224 Gas exchange, 190, 214, 224 Gastric, 190, 192, 196 Gastrin, 84, 190, 193 Gastroesophageal Reflux, 4, 190 Gastrointestinal, 134, 177, 178, 180, 187, 190, 217, 218, 220, 223 Gastrointestinal tract, 180, 190, 217, 218, 223 Gene Deletion, 60, 190 Gene Expression, 38, 50, 84, 190 Generator, 35, 39, 190 Genetic Markers, 37, 190 Genetics, 14, 17, 25, 59, 190, 196 Genotype, 69, 190, 207 Geriatric, 23, 37, 66, 71, 82, 116, 118, 191 Gland, 170, 191, 199, 206, 211, 216, 219, 221, 222 Glucose, 24, 37, 44, 52, 55, 71, 82, 84, 116, 117, 176, 191, 195 Glucose tolerance, 44, 191 Glucose Tolerance Test, 44, 191 Glutamate, 40, 47, 55, 191 Glutamic Acid, 191, 211 Glutamine, 55, 191 Glycogen, 55, 191 Glycoprotein, 191, 196, 223 Gonad, 191 Gonadal, 6, 191, 219 Governing Board, 191, 210 Grade, 5, 191

231

Graft, 191, 193 Granulocytes, 191, 217 Guanylate Cyclase, 191, 204 Gyrus Cinguli, 191, 198 H Habitual, 7, 10, 44, 58, 83, 179, 192 Habituation, 75, 192 Headache, 4, 177, 192 Headache Disorders, 4, 192 Health Status, 11, 192 Heart attack, 178, 192 Hemicrania, 192 Hemodilution, 91, 192 Hemorrhage, 183, 192, 219 Hemostasis, 192, 217 Hepatic, 170, 191, 192, 201, 209 Hereditary, 192, 202 Heredity, 190, 192 Heritability, 25, 192 Heterogeneity, 24, 170, 192 Heterozygotes, 56, 192 Hippocampus, 47, 52, 56, 184, 192, 198, 217, 220 Histamine, 27, 192, 193 Histidine, 192, 193 Hoarseness, 140, 193 Homeostasis, 14, 16, 18, 25, 28, 52, 85, 193, 218 Homogenate, 26, 193 Homogeneous, 182, 193 Homologous, 17, 171, 192, 193, 216, 220 Hormonal, 6, 67, 83, 111, 144, 174, 188, 193 Host, 11, 68, 193, 194, 224, 225 Hybridomas, 193, 196 Hydrogen, 169, 171, 175, 178, 193, 201, 205, 207, 212 Hydroxylation, 193, 223 Hydroxylysine, 181, 193 Hydroxyproline, 181, 193 Hyperalgesia, 6, 193 Hyperlipidemia, 28, 193 Hypersensitivity, 171, 193, 215, 216 Hypertension, 28, 105, 178, 193, 196 Hyperthermia, 14, 193 Hypnotic, 35, 38, 83, 101, 111, 119, 193, 198 Hypophyseal, 193, 200 Hypothalamic, 6, 38, 41, 57, 60, 111, 193 Hypothalamus, 13, 27, 41, 49, 174, 184, 187, 193, 198, 200, 210, 217, 218, 220, 221 Hypothermia, 192, 194 Hypoxemia, 43, 44, 194 Hypoxia, 18, 47, 52, 64, 194

232

Sleep Deprivation

I Ibotenic Acid, 194, 202 Id, 114, 122, 158, 164, 166, 194 Imipramine, 180, 194 Immune function, 6, 102, 194 Immune response, 54, 95, 144, 173, 174, 194, 216, 220, 224, 225 Immune Sera, 194 Immune system, 6, 9, 45, 140, 174, 186, 194, 199, 202, 224 Immunity, 54, 194, 223 Immunization, 54, 194, 216 Immunohistochemistry, 26, 47, 194 Immunologic, 194 Immunology, 170, 194, 196 Impairment, 24, 25, 28, 36, 85, 94, 144, 194, 200, 212 In vitro, 13, 23, 47, 61, 176, 194 In vivo, 23, 27, 37, 194, 201 Incision, 194, 196 Incompetence, 190, 194 Incontinence, 194, 216 Indicative, 137, 194, 206, 224 Induction, 23, 26, 38, 47, 60, 132, 195, 211 Inertia, 135, 195 Infant, Newborn, 170, 195 Infarction, 91, 183, 195, 201 Infection, 194, 195, 199, 207, 215, 219 Inflammation, 7, 13, 20, 48, 54, 140, 170, 173, 181, 183, 184, 195, 215 Ingestion, 3, 191, 195, 209 Initiation, 128, 134, 195 Inotropic, 185, 195 Insight, 28, 36, 60, 63, 195 Insomnia, 3, 10, 11, 35, 40, 46, 54, 57, 74, 83, 122, 128, 133, 134, 138, 139, 195, 223 Institutionalization, 26, 195 Insulin, 4, 28, 44, 52, 191, 195, 223 Insulin-dependent diabetes mellitus, 195 Intensive Care, 8, 60, 94, 195 Interleukin-1, 30, 96, 195 Interleukin-2, 195 Interleukin-6, 61, 144, 196 Intermittent, 18, 43, 44, 52, 196, 198 Internal Medicine, 110, 187, 196 Interneurons, 42, 196 Interstitial, 4, 139, 188, 196 Intervention Studies, 8, 196 Intestinal, 191, 196 Intestines, 169, 190, 196 Intoxication, 28, 91, 144, 196, 226

Intracellular, 46, 61, 62, 177, 195, 196, 204, 211, 213, 216, 217 Intracranial Hypertension, 192, 196, 222 Intrinsic, 14, 157, 170, 196 Intrinsic Factor, 157, 196 Invasive, 15, 37, 39, 49, 127, 194, 196, 199 Investigative Techniques, 5, 196 Involuntary, 133, 176, 185, 196, 202, 214, 218 Ion Channels, 174, 196, 204, 220 Ionizing, 187, 196, 217 Ions, 127, 175, 185, 193, 196 Irritable Bowel Syndrome, 157, 196 Ischemia, 174, 197 J Jet lag, 31, 35, 134, 197 Joint, 197, 218 K Kainic Acid, 35, 197 Kb, 150, 197 Kidney Failure, 187, 197 Kinetic, 196, 197 L Lactation, 197, 211 Lag, 31, 134, 197 Large Intestine, 184, 196, 197, 213, 218 Latency, 47, 51, 75, 89, 103, 112, 197 Latent, 119, 197 Length of Stay, 8, 197 Leptin, 28, 44, 52, 197 Lesion, 197, 198, 217 Leucine, 175, 197 Leukocytes, 176, 191, 197, 202, 223 Library Services, 164, 197 Lice, 61, 197 Life cycle, 176, 185, 197 Ligands, 178, 198 Limbic, 57, 85, 117, 118, 172, 192, 198, 210 Limbic System, 117, 172, 192, 198, 210 Linkage, 16, 190, 198 Lipid, 179, 195, 198 Lithium, 88, 89, 95, 111, 112, 198 Liver, 169, 170, 173, 175, 180, 184, 186, 190, 191, 192, 198, 201, 215 Liver scan, 198, 215 Localization, 61, 64, 194, 198, 199 Locomotion, 198, 208 Locomotor, 29, 198 Locus Coeruleus, 27, 32, 198 Longitudinal study, 14, 53, 198 Long-Term Care, 10, 198 Long-Term Potentiation, 47, 198

Index

Lorazepam, 77, 198 Lower Esophageal Sphincter, 190, 199 Lumbar, 83, 199 Luteal Phase, 43, 199 Lutein Cells, 199, 211 Lymph, 174, 187, 199 Lymph node, 174, 199 Lymphocyte, 89, 173, 199, 200 M Macrophage, 195, 199 Magnetic Resonance Imaging, 199, 215 Magnetic Resonance Spectroscopy, 85, 96, 199 Magnetoencephalography, 127, 199 Malaise, 134, 199 Malnutrition, 8, 170, 174, 199 Mania, 90, 98, 112, 199 Manic, 198, 199, 212 Manic-depressive psychosis, 199, 212 Maprotiline, 100, 199 Mastication, 200, 223 Mechanical ventilation, 8, 200 Medial, 51, 97, 119, 191, 200, 205, 217 Median Eminence, 41, 200 Mediate, 19, 178, 185, 200 Mediator, 22, 45, 195, 200, 217 MEDLINE, 151, 200 Meiosis, 200, 220 Melanin, 198, 200, 208, 224 Membrane, 16, 174, 179, 181, 182, 184, 188, 196, 200, 201, 202, 208, 217, 220 Memory, 19, 21, 33, 35, 36, 38, 47, 48, 55, 58, 64, 67, 75, 134, 140, 184, 198, 200 Meninges, 179, 183, 200 Menopause, 4, 200, 209 Menstrual Cycle, 43, 73, 75, 104, 199, 200, 210 Menstruation, 199, 200, 210 Mental Disorders, 129, 200, 212 Mental Health, iv, 6, 12, 19, 128, 129, 150, 152, 200, 212 Mental Processes, 185, 200, 212 Mercury, 111, 200 Mesencephalic, 198, 200 Meta-Analysis, 80, 200 Metabolite, 43, 176, 180, 201, 204 Metastasis, 179, 201 Methamphetamine, 15, 201 Methionine, 175, 201 MI, 139, 156, 167, 201 Microbe, 201, 222 Microbiology, 169, 174, 201

233

Microcirculation, 192, 201 Microdialysis, 27, 49, 50, 60, 201 Mitosis, 173, 201 Mode of Transmission, 16, 201 Modification, 91, 201, 212 Molecule, 173, 175, 181, 185, 186, 187, 201, 205, 213, 217, 224 Monitor, 19, 24, 49, 183, 201, 204 Monoamine, 37, 57, 91, 172, 184, 201 Monoamine Oxidase, 172, 184, 201 Monocular, 48, 202 Monocytes, 195, 196, 197, 202 Mononuclear, 202, 223 Monotherapy, 23, 66, 202 Morphine, 29, 173, 202, 205 Motility, 202, 217 Motion Sickness, 202, 216 Motor Activity, 19, 27, 56, 202 Motor nerve, 202, 204 Movement Disorders, 3, 186, 202 Mucosa, 202, 211 Muscimol, 50, 202 Mutagenic, 202, 217 Mydriatic, 202, 216 Myocardium, 201, 202 N Naive, 47, 202 Naloxone, 175, 202 Narcolepsy, 26, 50, 89, 139, 184, 202 Narcotic, 189, 202 Natural selection, 175, 202 NCI, 1, 129, 149, 180, 202 Necrosis, 173, 195, 201, 203 Need, 3, 7, 8, 11, 20, 38, 132, 138, 139, 159, 170, 191, 203, 222 Neocortex, 47, 203 Neonatal, 17, 63, 203 Nerve, 6, 40, 170, 171, 172, 174, 184, 198, 200, 201, 202, 203, 204, 209, 219, 223, 224, 225 Nervous System, 6, 17, 39, 169, 170, 172, 174, 175, 177, 179, 180, 184, 188, 190, 191, 200, 201, 202, 203, 207, 209, 216, 217, 220 Nervousness, 53, 203 Neural, 36, 38, 39, 48, 52, 79, 92, 96, 127, 170, 201, 203, 216 Neuralgia, 4, 203 Neuroanatomy, 24, 37, 198, 203 Neuroblastoma, 23, 203 Neuroendocrine, 6, 20, 37, 41, 92, 93, 103, 203

234

Sleep Deprivation

Neuroendocrinology, 20, 67, 84, 203 Neurologic, 157, 203 Neurology, 14, 16, 21, 27, 33, 36, 41, 53, 56, 64, 65, 66, 72, 74, 79, 83, 89, 93, 105, 111, 203 Neuromuscular, 169, 203 Neuromuscular Junction, 169, 203 Neuronal, 12, 19, 23, 32, 46, 47, 49, 55, 60, 62, 63, 203 Neuropeptide, 42, 203 Neurophysiology, 19, 32, 67, 69, 79, 82, 83, 84, 92, 94, 99, 103, 104, 106, 112, 116, 184, 203 Neurotoxicity, 33, 197, 203 Neurotoxin, 33, 203 Neurotransmitters, 46, 171, 203, 204, 210, 218 Niacin, 204, 223 Nitric Oxide, 49, 204 Nitrogen, 93, 171, 189, 191, 204, 223 Nocturia, 5, 204 Norepinephrine, 32, 170, 171, 185, 204 Nortriptyline, 23, 66, 204 Nuclear, 132, 175, 186, 198, 203, 204, 209, 221 Nuclei, 13, 38, 172, 186, 187, 199, 201, 204, 212, 216, 225 Nucleic acid, 169, 204 Nucleus, 35, 39, 41, 49, 173, 180, 183, 186, 198, 200, 202, 204, 210, 211, 212, 217, 218, 225 O Occipital Lobe, 204, 225 Ocular, 204, 215 Oculomotor, 94, 108, 200, 204 Oestradiol, 75, 204 Oncogene, 50, 204 Opacity, 184, 205 Opioid Peptides, 205 Opium, 202, 205 Optic Chiasm, 193, 205, 210, 220 Orgasm, 186, 205 Orofacial, 3, 205 Osteoporosis, 188, 205 Outpatient, 205 Ovalbumin, 54, 205 Ovary, 188, 191, 205 Overweight, 28, 44, 113, 205 Ovulation, 43, 199, 205 Ovum, 197, 205, 210, 211, 226 Oxidation, 55, 169, 176, 205 Oxygen Consumption, 188, 205, 214

Oxygenation, 194, 205 P Pacemaker, 20, 35, 38, 62, 205 Pain Threshold, 91, 205 Palate, 43, 206, 218, 224 Palliative, 206, 221 Pancreas, 169, 175, 184, 195, 206, 218, 223 Pancreatic, 190, 206 Pancreatic Juice, 190, 206 Panic, 189, 194, 206 Panic Disorder, 189, 194, 206 Parasitic, 197, 206 Parietal, 64, 206 Parietal Lobe, 206 Parkinsonism, 173, 206 Paroxetine, 19, 23, 66, 206 Paroxysmal, 192, 206 Partial remission, 206, 214 Parturition, 206, 211 Pathogenesis, 44, 206 Pathologic, 173, 182, 193, 206, 209, 224 Pathologic Processes, 173, 206 Pathologies, 41, 206 Pathophysiology, 5, 55, 134, 206 Patient Education, 156, 162, 164, 167, 206 Pediatrics, 12, 43, 47, 54, 96, 207 Penicillin, 172, 207, 224 Penile Erection, 110, 207 Penis, 186, 207 Peptide, 23, 69, 110, 175, 197, 205, 207, 209, 212, 222 Perception, 6, 140, 207, 215 Perfusion, 51, 194, 207 Peripheral Nervous System, 207, 210, 218, 220 Peripheral vision, 207, 225 Pernicious, 196, 207 Pernicious anemia, 196, 207 PH, 50, 101, 117, 120, 207 Pharmacokinetic, 207 Pharmacologic, 37, 64, 172, 207, 222 Pharmacotherapy, 37, 207 Pharynx, 190, 207, 224 Phenotype, 12, 25, 190, 207 Phentermine, 65, 81, 207 Phenylalanine, 208, 223 Phospholipases, 208, 217 Phospholipids, 189, 208 Phosphorous, 40, 208 Phosphorus, 177, 208 Phosphorylation, 61, 208 Phototherapy, 208, 216

Index

Physiologic, 23, 62, 170, 175, 200, 208, 211, 213 Pilot study, 66, 85, 88, 89, 208 Pineal Body, 187, 208 Pineal gland, 35, 111, 208 Pitch, 208, 225 Placenta, 188, 208, 210 Plants, 171, 174, 178, 179, 180, 191, 204, 208, 209, 222 Plasma, 20, 61, 67, 69, 95, 96, 110, 170, 172, 179, 191, 192, 197, 208, 216 Plasticity, 48, 56, 63, 106, 208 Platelet Activation, 208, 217 Platelet Aggregation, 204, 209 Platelets, 91, 204, 208, 209, 221 Poisoning, 173, 196, 200, 209, 217 Polymorphism, 68, 86, 94, 209 Polypeptide, 171, 181, 209, 210, 218 Polysaccharide, 173, 209 Polyuria, 5, 209 Pons, 85, 177, 189, 209 Pontine, 119, 209 Portal System, 200, 209 Posterior, 64, 172, 179, 185, 187, 204, 206, 208, 209, 224 Postmenopausal, 22, 188, 205, 209 Postnatal, 17, 209 Postoperative, 69, 209 Postoperative Complications, 69, 209 Postsynaptic, 49, 209, 217, 220 Post-traumatic, 192, 202, 209 Postural, 93, 97, 209 Potentiate, 19, 209 Potentiating, 171, 209 Potentiation, 118, 198, 209, 217 Power Plants, 132, 209 Practicability, 209, 223 Practice Guidelines, 152, 210 Precipitating Factors, 192, 210 Precursor, 173, 179, 185, 186, 187, 204, 208, 210, 223, 224 Prefrontal Cortex, 23, 64, 97, 119, 210 Premedication, 210, 216 Premenstrual, 73, 75, 104, 210 Preoptic Area, 27, 38, 50, 210 Presynaptic, 40, 174, 210, 220 Presynaptic Terminals, 174, 210 Prevalence, 10, 28, 39, 44, 74, 210 Probe, 9, 56, 64, 98, 201, 210 Progesterone, 210, 211, 219 Progression, 172, 210

235

Progressive, 16, 58, 135, 179, 184, 188, 191, 203, 208, 210 Projection, 196, 204, 210 Prolactin, 41, 70, 73, 75, 93, 94, 95, 98, 101, 118, 210 Proline, 181, 193, 211 Promoter, 68, 86, 211 Prophase, 211, 220 Prophylaxis, 210, 211, 224 Propofol, 60, 211 Prospective Studies, 21, 211 Prospective study, 79, 104, 198, 211 Prostaglandin, 81, 211 Prostaglandins A, 211 Prostate, 175, 211, 223 Protein S, 26, 36, 138, 175, 211, 215 Protocol, 7, 10, 13, 34, 36, 56, 212 Protons, 193, 196, 199, 212, 213 Proximal, 185, 210, 212, 216 Pruritus, 4, 212 Psychiatric, 31, 45, 67, 70, 76, 82, 99, 100, 102, 108, 119, 200, 212, 218 Psychic, 212, 216 Psychology, 20, 49, 70, 76, 101, 105, 110, 113, 185, 212 Psychomotor, 29, 32, 38, 106, 125, 177, 212 Psychopathology, 15, 212 Psychosis, 100, 107, 212 Psychotomimetic, 172, 184, 212 Puberty, 44, 212 Public Health, 20, 28, 40, 61, 145, 152, 212 Public Policy, 38, 62, 151, 212 Pulmonary, 13, 49, 170, 176, 182, 188, 197, 212, 224, 225 Pulmonary Artery, 176, 212, 225 Pulse, 51, 138, 201, 212 Q Quality of Life, 21, 27, 35, 212 Quaternary, 213, 216 R Race, 44, 213 Radiation, 174, 186, 187, 193, 196, 213, 215, 217, 226 Radioactive, 174, 176, 193, 198, 204, 213, 215 Radiopharmaceutical, 190, 213 Railroads, 132, 213 Random Allocation, 213 Randomization, 46, 213 Randomized, 11, 21, 22, 23, 24, 30, 36, 38, 45, 51, 186, 213

236

Sleep Deprivation

Reaction Time, 32, 86, 95, 101, 106, 117, 118, 134, 213 Reality Testing, 212, 213 Receptors, Serotonin, 213, 217 Recombination, 190, 213 Rectal, 72, 93, 213 Rectum, 173, 176, 184, 190, 194, 197, 211, 213 Recuperation, 11, 213 Recur, 213, 216 Recurrence, 180, 199, 213, 216 Refer, 1, 181, 189, 196, 198, 202, 212, 214 Reflex, 189, 214 Refractory, 21, 214 Regimen, 4, 186, 207, 214 Regurgitation, 190, 214 Relapse, 9, 40, 95, 112, 214 Reliability, 34, 214 Remission, 4, 48, 199, 213, 214 Research Design, 57, 214 Research Support, 6, 214 Resident physician, 88, 214 Respiration, 39, 133, 173, 178, 201, 214 Respirator, 200, 214, 224 Respiratory failure, 214, 224 Respiratory Physiology, 104, 214, 224 Response rate, 22, 23, 214 Restoration, 214, 226 Resuscitation, 28, 214 Retinal, 202, 205, 214 Retrospective, 21, 214 Reverse Transcriptase Polymerase Chain Reaction, 31, 215 Rheumatic Diseases, 6, 215 Rheumatism, 215 Rheumatoid, 4, 54, 215 Rheumatoid arthritis, 4, 54, 215 Ribose, 169, 215 Ribosome, 215, 223 Risk factor, 20, 24, 41, 44, 211, 215 Risk-Taking, 9, 215 Rod, 174, 180, 215 S Saccades, 79, 215 Saliva, 215 Salivary, 10, 31, 57, 62, 81, 184, 215 Salivary glands, 184, 215 Scans, 24, 215 Schizoid, 215, 226 Schizophrenia, 26, 32, 37, 63, 215, 226 Schizotypal Personality Disorder, 215, 226 Scopolamine, 33, 91, 215

Screening, 7, 19, 21, 180, 216 Seasonal Affective Disorder, 54, 103, 216 Second Messenger Systems, 204, 216 Secretion, 20, 41, 61, 75, 94, 112, 180, 192, 195, 197, 216 Secretory, 61, 74, 216, 220 Sedative, 35, 60, 171, 194, 199, 216 Sedentary, 22, 216 Segregation, 17, 213, 216 Seizures, 21, 65, 81, 92, 104, 113, 118, 127, 177, 206, 216 Self Care, 139, 216 Semen, 186, 211, 216 Sensibility, 172, 193, 216 Sensitization, 29, 216 Sensor, 18, 216 Septal, 198, 216 Septal Nuclei, 198, 216 Septicemia, 41, 217 Serum, 52, 72, 75, 82, 87, 101, 170, 181, 194, 217, 223 Sex Characteristics, 169, 212, 217, 221 Shedding, 40, 217 Shock, 217, 223 Side effect, 35, 170, 198, 199, 217, 222 Signal Transduction, 13, 47, 61, 217 Signs and Symptoms, 214, 217 Sister Chromatid Exchange, 102, 217 Skeletal, 180, 217 Skeleton, 197, 211, 217, 218 Skull, 183, 218, 221 Sleep apnea, 3, 4, 18, 20, 21, 34, 36, 39, 43, 44, 47, 61, 64, 134, 139, 156, 218 Sleep Bruxism, 3, 218 Small intestine, 218 Smooth muscle, 177, 192, 202, 218, 220 Sneezing, 217, 218 Snoring, 3, 18, 43, 44, 156, 218 Social Environment, 213, 218 Social Isolation, 8, 215, 218 Social Support, 218, 219 Solitary Nucleus, 174, 218 Somatic, 169, 198, 200, 201, 207, 210, 217, 218, 224 Somatostatin, 42, 218 Soporific, 27, 218 Spastic, 196, 218 Specialist, 11, 158, 219 Species, 59, 63, 187, 200, 201, 206, 213, 219, 220, 223, 225, 226 Spinal cord, 173, 177, 179, 200, 203, 207, 214, 219, 220

Index

Spirometry, 13, 44, 219 Stabilization, 28, 219 Staging, 215, 219 Statistically significant, 36, 219 Steel, 180, 219 Steroid, 183, 219 Stimulant, 16, 172, 177, 184, 192, 201, 207, 219, 224 Stimulus, 11, 101, 185, 186, 188, 196, 197, 213, 214, 219, 221, 225 Stomach, 169, 184, 188, 190, 191, 193, 196, 199, 207, 218, 219 Stool, 194, 196, 197, 219 Stress management, 45, 219 Stroke, 43, 127, 129, 150, 178, 219 Subarachnoid, 189, 192, 219 Subclinical, 195, 216, 219 Subiculum, 192, 220 Subspecies, 219, 220 Substance P, 201, 216, 220 Suppression, 49, 67, 76, 99, 111, 220 Suprachiasmatic Nucleus, 35, 39, 220 Sympathetic Nervous System, 174, 220 Sympathomimetic, 172, 184, 185, 187, 201, 204, 207, 220 Symptomatic, 5, 26, 220 Synapses, 198, 204, 220 Synapsis, 220 Synaptic, 32, 47, 48, 56, 198, 217, 220 Synaptic Transmission, 47, 220 Synergistic, 211, 220 Systemic, 4, 40, 41, 42, 176, 187, 195, 196, 209, 217, 220, 223 Systolic, 193, 221 T Telencephalon, 175, 221 Temperament, 57, 221 Temporal, 10, 32, 39, 172, 192, 221 Temporal Lobe, 172, 221 Testis, 188, 221 Testosterone, 75, 93, 118, 221 Thalamus, 52, 184, 187, 198, 210, 221 Therapeutics, 196, 202, 221 Thermal, 185, 221 Thermoregulation, 14, 221 Third Ventricle, 187, 194, 200, 208, 221 Thorax, 199, 221, 224 Threshold, 133, 188, 193, 221 Thrombocytes, 209, 221 Thrombosis, 212, 219, 221 Thrombus, 183, 195, 209, 221 Thymus, 194, 221

237

Thyroid, 41, 44, 73, 96, 99, 101, 102, 106, 221, 222, 224 Thyroid Gland, 221, 222 Thyroid Hormones, 96, 101, 102, 221, 222, 224 Thyrotropin, 93, 111, 118, 222 Thyroxine, 170, 208, 222 Time Management, 219, 222 Tinnitus, 157, 222, 225 Tolerance, 191, 222 Tomography, 37, 199, 222 Tooth Injuries, 218, 222 Tooth Preparation, 169, 222 Torsion, 195, 222 Toxic, iv, 140, 174, 175, 187, 194, 222 Toxicity, 116, 185, 200, 222 Toxicokinetics, 222 Toxicology, 152, 222 Toxins, 173, 195, 217, 222 Trachea, 177, 207, 221, 222 Traction, 180, 222 Transduction, 217, 222 Transfection, 175, 222 Transfer Factor, 194, 223 Transgenes, 60, 223 Translation, 9, 12, 223 Transmitter, 169, 174, 185, 196, 200, 204, 220, 223 Transplantation, 194, 223 Trauma, 133, 203, 223 Treatment Outcome, 37, 82, 118, 223 Triazolam, 134, 223 Tricyclic, 5, 171, 180, 194, 199, 223 Trigeminal, 4, 223 Tryptophan, 50, 110, 181, 217, 223 Tryptophan Hydroxylase, 50, 223 Tuberculosis, 182, 223 Tumor marker, 175, 223 Tumor Necrosis Factor, 31, 61, 223 Type 2 diabetes, 52, 223 Tyrosine, 33, 65, 81, 122, 185, 223 U Unconscious, 172, 194, 224 Urethra, 207, 211, 224 Urinary, 42, 71, 107, 183, 194, 209, 216, 224 Urine, 5, 43, 107, 121, 156, 169, 173, 176, 183, 185, 194, 209, 224 Uvula, 218, 224 V Vaccination, 144, 224 Vaccine, 212, 224 Vagal, 13, 44, 224

238

Sleep Deprivation

Vagina, 184, 200, 224 Vagus Nerve, 218, 224 Valine, 113, 224 Vascular, 20, 24, 187, 192, 195, 201, 204, 208, 221, 224 Vasoconstriction, 187, 224 Vasodilator, 177, 185, 192, 224 Vasomotor, 188, 224 Vector, 222, 224 Vein, 204, 224 Venous, 212, 224 Ventilation, 8, 224 Ventilator, 8, 200, 214, 224 Ventral, 23, 51, 97, 119, 193, 204, 209, 224 Ventricle, 172, 192, 212, 221, 224 Verbal Learning, 68, 225 Vesicular, 57, 62, 225 Vestibulocochlear Nerve, 222, 225 Vestibulocochlear Nerve Diseases, 222, 225 Veterinary Medicine, 151, 225 Viral, 60, 140, 222, 225 Viral vector, 60, 225

Virulence, 174, 222, 225 Virus, 179, 222, 225 Visceral, 174, 198, 224, 225 Visceral Afferents, 174, 224, 225 Visual Cortex, 48, 225 Visual field, 78, 205, 225 Vitro, 225 Vivo, 23, 82, 225 Voice Disorders, 140, 225 Volition, 196, 225 W Wakefulness, 15, 20, 25, 27, 38, 40, 46, 55, 56, 60, 62, 87, 89, 100, 104, 118, 133, 225 Weight Gain, 4, 44, 189, 216, 225 Windpipe, 177, 207, 221, 226 Withdrawal, 35, 40, 53, 226 Womb, 134, 226 Wound Healing, 179, 226 X Xenograft, 172, 226 X-ray, 182, 204, 215, 226 Y Yeasts, 207, 226

Index

239

240

Sleep Deprivation